Good afternoon and Welcome to the presentation of the INCREASE Study Results in Pulmonary Hypertension Associated with Interstitial Lung Disease. I'm Dewey Steadman, Head of Investor Relations at United Therapeutics. Please note that our presentation today will include forward-looking statements, and I encourage you to read the risk factors in our most recent quarterly and annual reports filed with the SEC for risks and uncertainties that may cause our actual results to differ. Today, we're pleased to have Dr. Steven Nathan, who's the Director of the Advanced Lung Disease Program and Director of the Lung Transplant Program at Inova Fairfax Hospital in Falls Church, Virginia, and a key INCREASE study investigator. Dr. Nathan will dive into the INCREASE results. Following Dr. Nathan's presentation, Michael Benkowitz, our President and Chief Operating Officer of United Therapeutics, will provide an update on our commercial plan in PH-ILD, assuming an April approval of the pending supplemental new drug application. Following Michael's presentation, we will host a Q&A session with Dr. Nathan, Dr. Leigh Peterson, our Vice President, Product Development, Michael, and James Edgemond, our CFO. Please note that if you've dialed in today's presentation and would like to ask a question, please email me at ir@unither.com so we can identify you before you ask your question. Given the opportunity to have two experts like Dr. Nathan and Dr. Peterson available for us, we ask that you limit your questions to the INCREASE data and our INCREASE specific commercial plans. Today's slide presentation is available on the Events and Presentations page at ir.unither.com. With that, I'll turn it over to Dr. Nathan. Thank you, Dewey. It's a pleasure being here today, thank you for the opportunity to present what I think is a very exciting and really groundbreaking study. It was a privilege for me to be part of the steering committee as well. A lot of this data that I'm presenting today, I did present at the American Thoracic Society meeting previously. I'll let everyone speed-read my bio, suffice it to say, I've been doing interstitial lung disease and pulmonary hypertension for the last 25, 30 years. This has been a particular interest of mine is the intersection of the two when pulmonary hypertension meets interstitial lung disease. I remember writing a state-of-the-art or perspective for our Blue Journal in 2007, where I provided the literature at that time linking pulmonary hypertension with IPF in particular. One of the subtypes, the subtype to the perspective that I wrote, was connecting the dots. I think that this study is really the final dot to be connected now that we have a treatment which helps patients with interstitial lung disease complicated with pulmonary hypertension. Let me see if I can advance. There we go. By way of further background, when we talk about pulmonary hypertension, there are five different groups. Group 1 or what we refer to as Pulmonary Arterial Hypertension are where all the PH medications are approved. There's only one that's approved outside Group 1, and that's riociguat, which is approved for CTEPH or chronic thromboembolic pulmonary hypertension, and that's Group 4. The two largest groups really when it comes to Pulmonary Hypertension are Group 2, which is Pulmonary Hypertension due to heart disease. Nothing's been shown to work there. What we're going to be talking about today, Group 3 Pulmonary Hypertension, where there's been nothing shown to work prior to the INCREASE study and which is a very large group as well. The two main subdivisions within lung disease are obstructive lung disease, primarily COPD, and interstitial lung disease, and that's where the INCREASE study was focused. Nothing approved in Group 3 yet. Everything that's available approved in Group I, and only one drug approved in Group 4. If we look at interstitial lung disease, it's a very broad group of different diseases, literally hundreds. If you open any textbook, 150-200 different causes of interstitial lung disease. Once pulmonary hypertension supervenes. I think there's a lot of emerging data that as the disease progresses, as interstitial lung disease progresses, invariably most of these do, then pulmonary hypertension supervenes. What you can see in the graph to the right, this is from a registry out of Europe, the COMPERA registry, is looking at the prognosis of idiopathic pulmonary arterial hypertension versus pulmonary hypertension related to IIP. As pulmonologists, we're very good with these different acronyms, which tends to confuse everyone, including ourselves. IIP are the Idiopathic Interstitial Pneumonias. That's one of the largest subgroups of ILD, the Idiopathic Interstitial Pneumonias. The prototypical illness under the IIPs is idiopathic pulmonary fibrosis, and that's where a lot of the data comes from. IIP, IPF, ILD, if nothing else, I'll confuse everyone by the end of the day. This is generally an overview of epidemiology of PH-ILD, so pulmonary hypertension complicating interstitial lung disease, and you can see estimates there of cases annually. What's interesting, if you look at ILD and you look at the actual incidence versus the prevalence, you can see that if we look at males to start, 31.5 new cases per 100,000, and the prevalence, 81 cases per 100,000. When you have an incidence that's very close to the prevalence, that tells you something about the prognosis of the disease. If you look at IPF in particular and look at the literature, median survival, three-five years prior to the antifibrotics. What we do know is that once pulmonary hypertension supervenes, then patients fall to the left of the curve. Once patients develop pulmonary hypertension in the context of ILD, their prognosis is significantly worse. If one looks at the incidence or the prevalence of IPF in particular, it is estimated anywhere from about 150 to 200,000, and IPF probably represents about one-third of all the interstitial lung diseases. If you look at the broad universe of interstitial lung disease, probably 500,000, 600,000, and that might even be an underestimate. I think we are seeing more ILD as we are dealing with an aging population. There is actually one study that is not shown here, looking at incidental evidence of interstitial lung disease in various populations, various registries, and it worked out that about 79% of patients who got CTs as screening for lung cancer had some evidence of interstitial lung disease. Some of those might stay stable, but some of those might go on to develop overt interstitial lung disease. I think ILD is kind of emerging as maybe a higher incidence than what we previously appreciated. You look at what's happening today with COVID, in particular, and we're seeing a good number of patients end up with residual interstitial lung disease after COVID. I digress a little bit. If you look at pulmonary hypertension and the incidence of pulmonary hypertension in ILD, it's very widely varied, from anywhere from 15% up to 86%. It really depends when in the disease course you look for it. If you look for it early, it'll be about 15% of the patients. If you look for it late, at around the time of transplant, it's around 85%, 86%. It seems invariable that as these diseases do progress, and invariably they do, at some point, they're all going to develop some measure of pulmonary hypertension. What is the mechanism of the pulmonary hypertension? It's much more complicated than we previously thought. We used to think that, well, very simple linear relationship. The more fibrosis, the more pulmonary hypertension. The more vessels that are destroyed, the more pulmonary hypertension. It's much more complicated than that, and there are probably a lot of interrelating factors involved. Sometimes the pulmonary fibrosis or the interstitial lung disease is not that bad, and the pulmonary hypertension is what we term disproportionate to the level of the underlying interstitial lung disease. I'm not going to get into this cartoon depiction. Suffice it to say, there are probably many elements that exist that lay the foundation for pulmonary hypertension. What's interesting is a concept that I refer to as cytokine crosstalk. In other words, some of the same cytokines that are important in the genesis of interstitial lung disease play a role in the genesis of pulmonary hypertension. That might be another factor that's involved. Looking at some of the studies that have been done previously, we'll start off with, at the top over here, sildenafil. Sildenafil was studied through the NIH IPF Network in a study called the STEP-IPF study that was published in the New England Journal in 2012. This was a negative study based on the primary endpoint of a 20% change in the six-minute walk test. Although certain metrics like quality of life, oxygenation, diffusing capacity, secondary endpoints did point in the right direction. There was a suggestion of some efficacy for sildenafil, but that hasn't been further validated. The endothelin receptor antagonists, of which there are three, bosentan, macitentan, ambrisentan, have all been studied in IPF in particular, but they were looked at for their antifibrotic effects and not for their PH effects. These studies invariably were agnostic to the presence of pulmonary hypertension. Although ambrisentan was looked at in pulmonary hypertension in particular, that was the ARTEMIS-IPF study, the ARTEMIS-PH study, but the ARTEMIS-PH study was stopped early when ARTEMIS-IPF was clearly a negative study. Riociguat has been studied in a very similar patient population to what we're going to be talking about. This was the RISE-IIP study. I was privileged to be the global PI for the study, and unfortunately, not only was it a negative study, but it was a harmful study. We actually got a call from the Data Safety Monitoring Committee saying, "We think you should stop your study." riociguat is actually contraindicated in idiopathic interstitial pneumonias, in interstitial lung disease because of the RISE-IIP study. I was also privileged to be the co-chair of the task force that wrote the last guidelines for Group III Pulmonary Hypertension, and these were published in the European Respiratory Journal early in 2019, so exactly two years ago now. We came up with this algorithm to try and help people work their way through Group III Pulmonary Hypertension. This is going to be much more of a hot topic, is when do you suspect it and when do you look for it, and when should you go seeking it? Previously, I think folks were a little bit nihilistic about pulmonary hypertension complicating interstitial lung disease, because the invariable response was, "Well, if I'm going to find it, what am I going to do about it?" Well, now there's going to be something to do about it, namely using inhaled treprostinil. I think the ante has been raised in terms of screening for pulmonary hypertension and looking to find it so that we can help these patients. This gets to the construct of the trying to differentiate Group 1 from Group 3 Pulmonary Hypertension. I'm not going to get into that because clearly now we have something that works for Group 3, whether it's Group 1 or Group 3 is not so important in interstitial lung disease anymore because we have a drug that works for both Group 1 and Group 3. This at the bottom over here, I remember sitting with my fellow task force members saying, "Hey, guys, we've got to say something more than this." There was really no data to support saying more than this other than individualized care. We couldn't be more prescriptive, even though I wanted us to be. There was nothing to say because there was no evidence to support any therapy. If we had to rewrite this algorithm and flowchart today, I think it would be quite a bit different. Let's move on to the INCREASE study, which was a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of inhaled treprostinil in patients with pulmonary hypertension due to interstitial lung disease, Group 3 PH. It was a one-to-one design. These were the inclusion criteria. Patients had to have various forms of interstitial lung disease, and I'll show you which forms qualified for the study. They had to have pulmonary hypertension documented by Right Heart Cath by the old definition. Mean PA pressure greater than 25, wedge less than 15 or equal to 15, so no Group 2 disease, and a PVR of at least three or more. They had to walk at least more than 100 meters, we didn't want them to be totally limited by their underlying lung disease. For those patients with IPF, they could be on one of the anti-fibrotics other than nintedanib or pirfenidone. We did include patients who had connective tissue disease. Now, connective tissue disease can give you Group 1 Pulmonary Hypertension, or you can have interstitial lung disease due to connective tissue disease, giving you Group 3 Pulmonary Hypertension. If they were included with connective tissue disease, we wanted to make sure that they had significant interstitial lung disease. For this group, in particular, their forced vital capacity needed to be less than 70% of predicted. I'm not going to read through all the key exclusionary criteria, they couldn't be on any other PH medication. They couldn't have any significant heart disease, couldn't be on too much oxygen, couldn't be actively engaged in pulmonary rehab or have a recent pulmonary embolism. This slide can be a little bit overwhelming. I warned you about interstitial lung disease and all the various subgroups. I'll just focus on a few over here. Here we have interstitial lung disease. What's in green is patients who could qualify for the clinical trial. The Idiopathic interstitial pneumonias, of which IPF is the most common. We have its less evil cousins, NSIP has a better prognosis. RB-ILD, DIP, these are respiratory bronchiolitis, interstitial lung disease, desquamative interstitial lung disease. These are significantly more rare than these other two. Very few patients who came in with these diagnoses. One condition that can be very difficult to differentiate from IPF and was included in the study is chronic hypersensitivity pneumonitis. Patients breathe something in, usually an antigen in bird poop is the major culprit for this, or molds can be a culprit for this, but this isn't idiopathic. There's no known cause. Chronic hypersensitivity pneumonitis. We did include CTDs, Connective Tissue Diseases, occupational lung disease, and then CPFE is the shortened acronym for combined pulmonary fibrosis and emphysema. That's a distinct subgroup that could be included as well. The primary endpoint was a change in the six-minute walk distance measured at peak exposure from baseline to week 16. 16-week study, and the walk had to be done between 10 to 60 minutes after the most recent dose of the medication. Secondary endpoints include a change in the NT-proBNP, so that's our biomarker between baseline and week 16. We had a composite endpoint of time to clinical worsening, and this composite was composed of varying components shown here. The first one was hospitalization due to cardiopulmonary indication, a decrease in the walk distance of at least 15% from baseline, all-cause mortality or lung transplantation. Other secondary endpoints included change in the peak six-minute walk at week 12 and change in the trough six-minute walk at week 15. All right. This gives you an idea of the time course of the clinical trial, screening, randomization, one to one. Half the patients got inhaled treprostinil, the other half, placebo. It's given four times a day. Patients were targeted to get nine breaths four times a day and could take as many as 12 breaths 4x a day. We try to get everyone up to at least nine breaths 4x a day. Try to come up with an apt description for these little, what looked like hanging chairs to me. I don't know what a hanging chair looks like, but that's the best description I could come up with. They're color-coded. The blues are the exploratory endpoints and when they were measured. The yellows are the secondary endpoints. The green is the primary endpoint at week 16, which was change in the six-minute walk distance. Looking at the baseline characteristics of the study population, they were well-matched. The mean age was 65 to 67. There was a little bit of a difference in gender distribution. More males in the placebo arm, actually, more females in the active treatment arm. That really didn't impact the study one way or the other. Looking at the etiologies of PH-ILD gives you an idea of the different prevalence of these different underlying disorders. Most of these patients had one of the idiopathic interstitial pneumonias. Seen over here, 40% versus 50%. Most of these were the most common form of that. That's idiopathic pulmonary fibrosis. CPFE 25%, 25%. CTD, 25% versus 20%. Other less common conditions, chronic hypersensitivity, there will be 6%, 5.5%. Most of these patients were on supplemental oxygen. Once you have pulmonary hypertension, you tend to have a little bit more severe disease, 73%, 70%. There were some who came in on anti-fibrotic therapy. These were mostly the IPF patients, and you can see the distribution here at the bottom between pirfenidone and nintedanib. They were a pretty sick group of patients based on their underlying six-minute walk distance, 254 versus 265. If you look at most of the PAH studies, mostly if you look at the baseline six-minute walk, it's generally around 320, 340 meters. A little bit more sick than that. They did have significant pulmonary hypertension with the PVR in the six range. The NT-proBNP was also elevated, m PAP, mean pulmonary artery pressure, 37, 36, and the wedge pressure was 10 and nine. Well-matched in all regards in terms of functional ability as well as their hemodynamics. Just looking at their PFTs now, we'll focus on the FVC because these are restrictive disorders, 62%, 63%. Little bit more severe than what we see in typical IPF studies, where most studies, the FVC of the group is around 70%. The DLCO, which tends to correlate with pulmonary hypertension, was also on the low end at around 30% and 28%. This shows you the screening randomization and follow-up. I'm not going to go through all of this. What I will say is that they were a sick group of patients, so there were some dropouts, but that appeared to be equivalent between the two arms, so that at 16 weeks we had 130 patients who completed in the TYVASO arm and 128 who completed in the placebo arm. Coming to the primary endpoint, remember now it was 16 weeks, we look at the change in the six-minute walk distance. It came out at 31 meters, favoring inhaled treprostinil. If we look at week 12, it was also around 31 meters. That, remember, was one of our secondary endpoints. Another of our secondary endpoints was the trough at 15 weeks, which was 22 meters. We know that TYVASO is given four times a day. There are going to be peaks and troughs. Even at the trough, there was a difference favoring inhaled treprostinil. 31.12 meters. To put this in perspective, when inhaled treprostinil got approved for PAH, for Group 1 Pulmonary Hypertension, that was a TRIUMPH study, and that was published in 2010, and the difference there was, I believe, 19 or 20 meters. At least numerically more than that, and right in the range of what we see in most of the clinical trials for Group 1 Pulmonary Arterial Hypertension in terms of the difference in the six-minute walk distance. This is a graphic depiction over time what we saw. The groups tended to separate out pretty early. You saw a difference as early as four weeks, certainly by eight weeks and then by 16 weeks. This just represents different statistical methodologies in terms of working out the difference. Whichever way we looked at it favored treprostinil significantly. Actually, what's also interesting, which I should also point out, is a lot of this difference was driven by improvement in the treprostinil group versus deterioration in the placebo arm. I think that's important that a lot of this difference was by improvement. It served to not only be different to the placebo arm, but actually there was a numeric increase in the walk distance for this group of patients. This is a forest plot looking at different subgroups. I think the bottom line message is that everything is to the right. Everything favors treprostinil. If we looked at it by age, by sex, by baseline six-minute walk distance, by baseline diffusing capacity. The one thing that you'll note here is that the higher the PVR, the more robust the response. What I would also point out, which was very nice to see, is an apparent dose response. For those patients who couldn't get up to the maximal number of breaths, you see less of a response. Once patients get to 10 to 12 breaths, you see a greater response, and those on the highest dose got the best response. That kind of validates the robustness of the underlying primary was at this dose response that we could see from these analyses. In terms of secondary endpoints, we met pretty much all of the secondary endpoints. Improvements in the NT-proBNP, reduction in time for clinical worsening. I showed you the data for week 12 as well as week 15 in the six-minute walk distance. The only things we didn't hit, which were further down on the list, were differences in our patient-reported outcomes, the St. George's Respiratory Questionnaire and the distance saturation product, which is gained from the six-minute walk distance, looking at the distance in relation to the oxygen saturation. The one thing I will say, which is always a concern with any vasodilating patients with underlying lung disease, is that there was no worsened oxygenation. There was no evidence of increased V/Q mismatch. That was one of our safety endpoints. This slide can be a little bit confusing when you look at it initially. I will walk you through it. This gets to the NT-proBNP. Let's look at baseline first. You can see at baseline that the treprostinil group had a higher NT-proBNP than the placebo arm, 550 versus 420. What happened over time to the treprostinil group? It went down 550 to 485 to 454. The placebo arm that started lower, started at 420, went to 528 and 590. It appeared that I apologize, I have background noise. I'm in my office at the hospital. Unfortunately, they tend to repeat that three times, and then they tell you that it's a false alarm the fourth time. Anyway, hopefully I made the point about the NT-proBNP. We had our biomarker going in the same direction, which was gratifying to see as well. Actually, it's a good time to take a water break for me until the operator gets through the announcement. All right. Well, let me try and talk through that. Kaplan-Meier plot of time to first clinical worsening event. Once again, this favored the inhaled treprostinil group. You can see the Kaplan-Meier plot here. There was a 39% risk reduction. If you look at the absolute risk, 22.7% in the inhaled treprostinil group versus 33% had clinical worsening over 16 weeks. That's quite a difference over a relatively short period of time. The next question we've always got to ask ourselves, see if we have that on the next slide, is what drove this difference in clinical worsening? Remember, it's a composite. What were the components of the composite that drove this? Here we see the numbers again, 22.7% versus 33.1. Hospitalization, there was a difference. 18 hospitalizations versus 24 cardiopulmonary hospitalizations. Difference or change in the walk distance of greater than 15% from baseline. This is a decrease, 13 versus 26, 8% versus 16%. Mortality was the same in the two arms, four and four in both arms. There were two lung transplants in the inhaled treprostinil arm. Hazard ratio shown over here, 0.61, 39% reduction. This was significant with the P value as shown of 0.02. Whenever we give an inhaled medication, we have to be sure that we are doing no harm. One of the safety measures was exacerbation of underlying lung disease. We wanted to make sure that those folks who got inhaled treprostinil didn't have increased exacerbations of their underlying lung disease. In fact, and indeed, it went the other way, that there were less exacerbations in the inhaled treprostinil arm versus the placebo arm. Even though this was a safety measure, it went in directionally favoring treprostinil in terms of reducing exacerbations of the underlying lung disease. You can see the numbers over here, 26% for inhaled treprostinil, 38% for the placebo patients. This was not centrally adjudicated. This was as determined by each site's principal investigator. In terms of the safety, the treatment was well-tolerated. The safety profile was consistent with previous studies of inhaled treprostinil. Most treatment-related adverse events were mild to moderate in intensity. 10% of the It shouldn't be oral treprostinil, it's inhaled treprostinil, sorry for the typo. 8% of the placebo patients prematurely discontinued due to an AE, so equivalence there. Serious AEs occurred in 23% of patients receiving inhaled treprostinil, 25.8% of placebo patients. Everything gets reported as an AE, and this is a sick group of patients, so good to see equivalence in that regard as well. This is a summary of the AEs. The ones that are bolded are actually favorable AEs, if you want to look at it that way. Dyspnea, increased shortness of breath, less in the inhaled treprostinil arm versus the placebo arm. NT-proBNP was also captured as an AE, and an increase in this was less 5.5% in the treatment arm versus 15.3% in the placebo arm. Other things like cough are to be expected in patients who have interstitial lung disease, and you always have to look at placebo-corrected, so 43% versus 33%, so placebo-corrected, that's more like 10% of the inhaled treprostinil arm had increased cough. Headache, not unexpected. This is a prostanoid, 27% versus 19%, so 8% placebo-corrected. The rest of these I'll let you read for yourselves. This was very interesting. Another safety measure was looking at the lung function. We were giving them an inhaled medication. They had interstitial lung disease. We wanted to make sure that this didn't have deleterious effects on their lung function. I'll focus you on the right first. Here we have inhaled treprostinil, and here we have placebo. Much like acute exacerbations of underlying lung disease, it went in a directionally favoring inhaled treprostinil. You can see a significant difference when expressed as% predicted between inhaled treprostinil and the placebo arm. That was a very pleasantly surprising finding that came out of the study. This is how we typically look at differences in forced vital capacity, and as most of you are probably aware, forced vital capacity has been the primary endpoint in pretty much all IPF clinical trials and ILD clinical trials, and that's what's gotten pirfenidone and nintedanib approved. If you look at it for the group as a whole, expressed in mLs, there's a difference numerically between the treprostinil arm and the placebo arm, but the error bars cross. This wasn't statistically significant. If you express it as percent predicted, it was, that's probably a function of the tighter standard deviation around the percent predicted versus the numbers in mLs. This is where it gets even more fascinating. This is a busy slide and a busy table. I'll point you to the subgroup analysis of the IIPs, the Idiopathic Interstitial Pneumonias, looking at the difference between the treatment arm in inhaled treprostinil and placebo. Let's go to mLs. Let's look at 16 weeks. Here you can see a difference favoring inhaled treprostinil of 108 ccs at 16 weeks in the subgroup with Idiopathic Interstitial Pneumonia. We'll make it even more interesting by going to the IPF group over here at 16 weeks, looking at the difference in mLs between the placebo and inhaled treprostinil arm, 168 ccs at 16 weeks of inhaled treprostinil. The p values for all of these subgroup analyses at 16 weeks was significant, 0.01. A very nice safety signal that perhaps suggests efficacy of inhaled treprostinil as an antifibrotic. This was a safety endpoint, so what I'm saying is perhaps somewhat speculative, but will be studied in a pivotal study to look at the potential antifibrotic effects of inhaled treprostinil. Additional safety measures or safety endpoints, no clinically relevant treatment-related changes in pulse ox or supplemental oxygen use were noted in the study period. PFTs, I alluded to, no safety signals there. Median improvement in percent predicted FVC at week 16 in the inhaled treprostinil group, I mentioned already. I mentioned as well, these numbers over here, I didn't get into in too much detail for the group as a whole. I think what was exciting in particular that I alluded to were the IIPs, the idiopathic interstitial pneumonias, and especially the IPF patients, 168 cc at 16 weeks. A sizable group of patients as well that demonstrated this difference. In conclusion, INCREASE is the largest and most comprehensive study of this patient population to date. Patients experienced significant improvements in their exercise capacity as early as eight weeks, with effects sustained throughout the 16-week period of the clinical trial. Patients also demonstrated improvements in other clinically meaningful outcomes, including the NT-proBNP, a decreased risk of clinical worsening, as well as a decreased risk of exacerbation of the underlying lung disease. The treatment was well-tolerated. There was no evidence of worsening oxygenation or increased V/Q mismatch, and there was evidence, a signal of an improvement in the FVC, especially in the IIP population and the IPF population. The results support an additional treatment avenue and might herald a shift in the clinical management of patients with interstitial lung disease. With that, I'd like to conclude, and I have to acknowledge all my co-investigators around the country who participated, all the patients who enabled the study to be positive, all the clinical coordinators who worked on enrolling these patients. I think I'd like to thank United Therapeutics, to be quite honest, taking on this big study, taking the risk of this big study, and coming up with a new treatment for our patients with this devastating complication of the underlying interstitial lung disease. At this point, I'll hand it over or back to Dewey. Thank you very much. I'll take questions at the end. Thanks, Dr. Nathan. Josh, our operator, can you put the presentation back up on the screen? I'm sorry. I knocked it off the screen. Next up will be Michael Benkowitz, UT's President and COO, who will discuss our commercial plans for INCREASE in PH-ILD. Great. Thanks, Dewey. Thanks, Dr. Nathan, for that excellent presentation. I'd also like to thank you and your fellow INCREASE Steering Committee members, Doctors Waxman and Tapson, for your leadership in this trial. I too would also like to thank all the investigators and patients that participated in INCREASE. We at UT are very excited about the results of this trial, and that we are on the verge of being able to bring a treatment to the estimated tens of thousands of patients with PH-ILD who have up till now had no approved treatment option. We're also very pleased that the results of the trial have been well received by the academic medical community. Much so that the data were published in the prestigious New England Journal of Medicine. This is the first time in UT's history that we've been honored to have one of our clinical trial results published in the New England Journal. It's very exciting for us as a company, and especially those in the company that contributed so much to designing and running this trial. As Dewey said, I'd like to spend the next few minutes providing an overview of the PH-ILD commercial opportunity, our launch readiness, and expectations. I was trying to buy you guys some time to get the presentation up. All right. Josh, do I have control? No. All right. Give us one second, guys. All right. There we go. Okay. Let me start off by framing things at a macro level, and this may be helpful for those of you that are on the call that are either new to or unfamiliar with United Therapeutics. We're a company focused on providing life-extending technologies to patients in really two core areas. The first is pulmonary arterial hypertension, or PAH, and the second is interstitial lung disease, or ILD. We have three primary medicines in the prostacyclin class of drugs approved for PAH, generating about $1.5 billion in revenues each year. We expect those PAH sales to grow each year through continued promotion and education about the benefits of our products, along with newer, more convenient delivery devices, formulations, and novel therapeutics that are in development. Today our focus though is on our first foray into ILD, and specifically pulmonary hypertension associated with ILD, an indication we expect to receive an approval for April. TYVASO would be the first product approved for these patients' pulmonary hypertension. This is just the beginning of our work in ILD. We have two more active phase III trials in this area. One is in pulmonary hypertension associated with COPD, and the other, as Dr. Nathan mentioned, is in pulmonary fibrosis without pulmonary hypertension, which we believe will be the first disease-modifying drug in this indication. Our deep pipeline also includes using xeno technology and 3D bioprinting to create an unlimited supply of transplantable kidneys, hearts, and lungs. Okay, we're talking about TYVASO today in the context of PH-ILD, but really this is a product that is positioned to significantly advance our growth in the near term. TYVASO was already approved in PAH, which as you can see at that sort of top left of the circle here, is a market of approximately 45,000 patients. As I said, we believe there are opportunities to grow TYVASO in this market, even though PAH is a crowded market, through continued education about the efficacy of prostacyclin therapy, along with a new, more convenient dry powder inhaled form of TYVASO that we expect to be approved and ready to launch by the end of the year. Moving to the right into PH-ILD, which is the focus of today's discussion, here's a market with conservatively 30,000 patients with no approved therapy. On the strength of the increased data, we're confident that we're going to be able to bring TYVASO to many of these patients. As we move to the bottom right, we move into pulmonary hypertension associated with COPD, which I mentioned a minute ago. This is another 100,000 potential patient population that currently has no approved therapy. Finally, if we go to the bottom left, we move to the 100,000-patient IPF market. Based on the improvement in forced vital capacity and reduction in underlying lung disease data that Dr. Nathan described from INCREASE, we have launched a phase III trial on IPF, an area where, as I said, there is no disease-modifying therapy. That's a virgin market opportunity of approximately 230,000 patients in ILD, in addition to the 45,000 patients in PAH. There we go. Okay. Let's drill down a little bit on the PH-ILD opportunity. Here we show the epidemiology of PH-ILD. I think Dr. Nathan covered this brilliantly in his presentation, but to state again, I think the data suggests that it would point to approximately 200,000 to 250,000 ILD patients in the U.S., and that an estimated 15%-86% have or could develop pulmonary hypertension. It is difficult to establish precise prevalence, since most of these estimates come from case reports and retrospective data. As we know, pulmonary hypertension is confirmed with a right heart cath, and frankly, the vast majority of these patients have not had a right heart cath because without an approved therapy, there's really no sense in putting the patient through this procedure. We point out here, as did Dr. Nathan, that as ILD advances, the frequency of PH continues to rise. We anchor and continue to anchor to the 30,000 patient population figure for PH-ILD. I think this information clearly suggests that this could be a very conservative figure. Okay, here, this Kaplan-Meier curve on the left I find fascinating. We can see that the prognosis difference of an ILD patient with pulmonary hypertension as compared to one without pulmonary hypertension is quite significant. I'll say that this has been a pretty powerful chart with the healthcare providers that we've shown this to in our market research and testing. They told us that this creates a strong and compelling case if a therapeutic option is available to evaluate ILD patients for pulmonary hypertension and hopefully change the course of these patients' progresses. That evaluation is really going to be key to our launch come in April. Okay, let's talk about that. How do we identify these patients? Dr. Nathan talked about the suspect, support, confirm framework, and we have already started discussing this framework with ILD treaters with an emphasis on screening early. In the suspect category, you're looking for some of the signs and symptoms listed here that are out of proportion to the underlying lung disease and/or signs of RV strain or failure. From there, you support the suspicion with an echo, and then based on the results of the echo, you finally confirm with a right heart cath. Over time, we expect that we'll fine-tune these criteria as we gather more data and work with physicians. As Dr. Nathan indicated, we believe this is a sound rubric for identifying these patients now. As I said, we have started the process of raising awareness around both the severity of pulmonary hypertension in these ILD patients and how to identify these patients as early as possible. Okay, next, let's talk a little bit about physician reaction to the INCREASE data. Obviously, I think you hear Dr. Nathan's enthusiasm with the data and its potential to help patients. I think the headline here really says it all. He's not alone. These physicians that see these patients, as Dr. Steven Nathan said, they're very sick patients. They're eager for a treatment that can improve their patients' outcomes and are excited about the potential for TYVASO to be that drug. Since unblinding the study last year, we've engaged in multiple investigator meetings, advisory boards with physicians, and market research activities. I think what you can see here on the slide are the key themes that we hear across all of these channels of input. Kind of key things we're hearing is that physicians believe that the INCREASE data will have a positive impact. They are motivated to screen more. Like I said, that's incredibly important to our launch and beyond. The data suggests that PH-ILD treatment will be augmented with a new, safe, effective treatment option. I think generally the physicians that have had an opportunity to see the INCREASE data are impressed with the data set as a whole, but in particular, they find the six-minute walk distance, the time to clinical worsening, and the reduced risk of exacerbations of underlying lung disease to be the most impactful of the data. They believe that TYVASO does have the potential to help these patients improve their condition. They found that the etiologies of the patients in the INCREASE study match what they're seeing in their clinic. Importantly, very importantly, they believe the data is going to change the way they practice medicine. With that, let's change gears a little bit and talk about our launch prep. An important factor in a successful commercial launch is obviously understanding who your customers are. Here we're really talking about a group of physicians that is new to us. In PAH, there are about 2,300 physicians, plus-minus, who are your main PAH doctors. In ILD, there are about 4,700 physicians, but about 1,700 of those are what we call our top decile doctors. For those of you that are not familiar with the concept of deciling, we place our doctors into deciles based on the number of patients they see. The higher decile doctor you are, the more patients you see, and the lower decile doctor you are, you see fewer patients in the disease area. What you can see here by the chart on the left is that you've got an overlap of about 1,300 physicians between PAH and ILD, which is about 30% of the ILD docs. In reality, that actually overstates things. Of the 1,300 overlap physicians, I would say most of those are primarily PAH docs that, for lack of a better word, dabble in seeing ILD patients. So they would be what we would consider low decile ILD doctors. There are not that many physicians, relatively speaking, that are both high PAH and high ILD treaters. As I said, we're really talking about a new base of doctors that we need to call on. Now, with our efforts to educate on the severity of pulmonary hypertension in these patients and the availability of a treatment option, some of these doctors may decide to refer their PH-ILD patients to PAH doctors. That's fine. Many have also indicated that they will treat these patients themselves. Either way, our commercial medical teams need to access these new physicians to make them aware that there is a treatment available or will be available, and advocate that they screen for pulmonary hypertension so that the patients have the opportunity to benefit from TYVASO. Okay. To pull this off effectively, we have to expand our commercial and medical organization for PH-ILD. We've expanded our field-based staff, comprised of sales representatives, nursing specialists, and medical science liaisons, by about 40%. We've restructured the team to provide more focus and reduce executional risk. We now have a team dedicated to promoting ORENITRAM and TYVASO in PAH. We have another team focused on detailing REMODULIN in PAH. Yet a third team that will focus exclusively on promoting TYVASO in PH-ILD. We started these expansion efforts last summer and have effectively completed our hiring. The new employees are on board and have gone through or are currently undergoing training right now. They're out starting to meet these new physicians in an appropriate and compliant way, and will be ready to hit the ground running at launch. Okay. Lastly, we get a lot of questions about how we think about uptake. As we said last week at the JPMorgan conference, our goal is to have at least as many patients on TYVASO and PH-ILD as we do in PAH within about 18 months post-launch. I'm not sure it's going to be a linear journey between here and 18 months. In fact, I'm pretty sure it won't be, but we know the patients and the opportunity are there for us. This comes with the usual caveats around we have to receive FDA approval in April, and there being no additional COVID-related delays or impacts in the spring and later this year. In summary, the key takeaways here are outlined here. Upon approval, we're entering a PH-ILD market with at least 30,000 patients and no other approved therapy. Physicians find the INCREASE data impactful. They're excited to have a treatment option and plan to use TYVASO. The staff expansion we need to support the launch is complete. We've started the process of increasing awareness around the impact of pulmonary hypertension on these patients and the need to screen early. We're looking forward to working toward our goal of doubling the number of TYVASO patients within about 18 months of launch. Just as a reminder, this is a really busy and exciting year for UT. While we spent today talking about our launch into PH-ILD, this is just one of four potential launches this year. The others being REMUNITY, our new sub-Q device for REMODULIN, which will launch imminently. Also, the implantable system for REMODULIN, a new intravenous device launching in the second half of 2021. Finally, TYVASO DPI, our dry powder inhaled form of TYVASO, which is currently on track to also launch by the end of the year. By the way, we expect that the approval of TYVASO DPI will apply to both our PAH and PH-ILD indications, thus offering a more convenient delivery system for TYVASO to both groups of patients. With that, I will turn things back over to Dewey, and we can move into the Q&A portion of the call. Thanks, Mike. Today for the Q&A, we'll be hosting it through the webcast itself. If you have a question to ask, feel free to hit the raise hand button. If you're on the phone, Josh from Zoom, how do people on the phone ask a question? They can raise their hand by hitting star nine, and we will be able to see their hand. All right, perfect. We have a couple people in the queue already. I guess the first question would be from Hartaj Singh with Oppenheimer. Oops. Hartaj, you just have to unmute yourself. Oh, sorry. Can you hear me now? Yep. Great. Thank you. This is a question for Dr. Nathan. In one of the slides, Michael had mentioned that doctors really like the significantly fewer lung exacerbations. It's almost by a third that TYVASO is decreasing lung exacerbations. I know that lung disease as diverse as COPD, asthma, cystic fibrosis, that decrease in lung exacerbations is actually considered a pretty important event. I guess lung exacerbations are considered a sentinel event. Would you agree with that, Dr. Nathan? How important do you think that is for TYVASO in PH-ILD? Thank you for the question. Sure. No, I think that's very important. As I mentioned, it was an unexpected, very pleasant surprise finding. If someone has an acute exacerbation, it has a lot of ramifications for the patient. They feel worse for whatever reason. They're more short of breath. They're coughing more. It's increased healthcare resource utilization, doctor visits, ER visits, maybe hospital admission. They require more medical attention. I think it's meaningful to everyone, the patients, the payers, everyone. We know certainly if patients are admitted to the hospital with interstitial lung disease, and I don't know how many of these were admitted, we don't have that data, or we do have that data, the hospitalization, the mortality over time is more, and their prognosis is generally significantly worse. How many of those acute exacerbations over time is at a precursor of other bad events happening further on down the road? It's quite possible. I think it is a pretty big deal. The one caveat I would say is when we look at acute exacerbations in many clinical trials as a primary endpoint, then typically they are adjudicated. These were investigator reported, but if it was important enough to the investigator, then it was certainly important enough and was meaningful to the patient and was truly an event. Let me leave it at that. All right. Great. Thank you, Hartaj and Dr. Nathan. Our next question will come from, I think it's Liana Massados, but she's showing up as [Sveta Dingy]. I've got to allow her to talk. If you could just unmute and ask your question. Okay. Thank you, Dewey. This is for Michael Benkowitz, a commercialization question. Can you characterize the physicians who treat PH-ILD versus PAH? Despite the unmet need, do you anticipate initial sales to be slow in a COVID environment? We are able to characterize those physicians or at least identify those physicians as compared to PAH and have done that, and as I said, we're out forming those relationships, engaging with those doctors. I think one of the interesting things will be, as I said, we're going to rely on those physicians to certainly screen these patients. Whether they decide to actually treat the patients or refer them to their colleagues over in the PH clinic, I think remains to be seen. I think it's still a little bit of an unknown right now in terms of how that's going to break out. As I said, a lot of the ILD docs have said they feel like they're going to be perfectly comfortable treating these patients. Others have said, "No, I'll probably refer them over to their PAH." We're covering both bases. We'll leave it up to the doctors and the institutions to figure out how that gets managed within the institution. As I said, we're covering both bases. I don't know about the COVID impact right now. Again, a gaining issue to getting approved is typically you need to have a Right Heart Cath in order to confirm diagnosis and get that approved for reimbursement. CMS, I think back last maybe April or May, instituted a temporary waiver on Right Heart Cath procedures for patients in PAH. As we read the language, that is actually not limited to PAH. It would extend to patients with pulmonary hypertension-associated interstitial lung disease. That gives us at least some comfort that the doctors will be able to start patients on therapy in lieu of having done a Right Heart Cath. They will eventually, at some point, have to come back and do the Right Heart Cath to confirm it. That waiver continues to exist, and it's being reviewed, I think, on an every 90-day basis. We expect that probably through at least the first half of this year, that will stay in place. If I may comment, because I see the COVID question come up in the chat box as well. Please. I think it's very hard to have any kind of medical conference or talk at this point without talking about COVID, especially to a pulmonologist, because it's affecting us all. This is an emerging issue, no doubt, as we talk about the long haulers. There are a number of patients, the numbers remain to be defined, who come into the hospital, languish in the hospital, and are left with residual fibrosis. What the natural history of these patients will be is unknown. I think that we're getting data every day on these patients. I just saw a paper, I think this week, that said, well, the incidence in patients who come into the hospital and end up needing oxygen is 5%-10%. Whether that holds out or not, whether one year into the pandemic, what's the natural history of these patients? Will they resolve over time, or will they be left with permanent injury to their lungs? I think a significant number will be left with a measure of fibrosis. We've had a number of patients who've been referred to us already for lung transplants post-COVID who have advanced fibrotic lung disease. I think it's still a little bit of a black box in terms of how many patients might be affected by this. Thanks, Dr. Nathan. Our next question will come from Joe Thome from Cowen and Company. Hi there. Thank you for taking my question. Just one for Dr. Nathan in terms of usage patterns. As soon as you sort of confirm PH-ILD in your patients, would you use TYVASO early on in the treatment course? Maybe on the flip side of that, is there a patient subtype or any sort of characteristics where you wouldn't consider intervening with TYVASO? I think for every patient who I document pulmonary hypertension, it is certainly something to consider and that I would use. In my experience so far, these patients have been very willing to try it and use it and be compliant with it. As opposed to, say, PAH patients. Sometimes these PAH patients have mild disease or are not that symptomatic, let me say that, or not on oxygen. For the most part, as you saw in the numbers, about three-quarters of these patients are on oxygen. They are limited already, and they are prepared to try anything that is going to help them in terms of their functional ability [inaudible]. I think an important point is if you compare and contrast this to, say, the antifibrotics, the antifibrotics slow the rate of degeneration. They don't make the patients feel better necessarily, and this is a medication that potentially will make the patients feel better and enable them to do more. And I think you could see that in the walk distance, which was mostly driven by improvement in the treatment arm. What's also very interesting to compare and contrast is when I showed you the FVC data, if you look at pirfenidone and nintedanib, both slopes go down, and the difference is driven by the rate of decrement in FVC over time. But it was interesting within health TYVASO, the difference between inhaled TYVASO and the placebo was driven in large part by improvement in FVC. Now, that's speculative, and that will be tested and trialed in the Teton study, but that was also a very nice, neat surprise to see was that there appeared to be actually a measure of improvement in the FVC in the treatment arm. Thanks. Our next question will come from [Sarah Badazi] of Jefferies. Oh, sorry, I didn't hear that again. Idon't know why it didn't came up. I think I shared the registered form of it. I have a couple of questions about the TYVESO and I have questions for Michael. The TYVASO, you have a 30,000 child of patients with [inaudible] could have been a conservatory. I mean, it could be up to like over 100,000 patients that identified in that post, based on patients in the study criteria, w hat percent of patients would be eligible for TYVASO? This is question number one. Number two is that you mentioned the patient's willingness to take it. What percent of a patient would be willing to take TYVASO in addition to oxygen supply? Once the patients get on the drug, what would be the adherence rate? Let me take them one at a time. I missed the last part of the question. I think that, certainly, these are patients who their prognosis is pretty poor, and anything that might help them in terms of doing more, their quality of life, I am going to offer it to the patients. Because they are feeling their disease, they are symptomatic. Most of them, in my experience, will elect to go on the medication, especially when they know that this could potentially result in improvement in how they are feeling. Patients who are tethered to their oxygen and are compromised already are very willing to try things that might help them. I think the uptake should be pretty good. I think you're right. I think the estimates presented are conservative, and Michael did allude to that. I think there are many of these patients out there, and you mentioned 100,000. It could be 100,000, could even be more than 100,000. We'll have to wait and see. If you look at that number, that 85% of them will eventually, at some point, develop pulmonary hypertension. It's just a question of discovering these patients and getting the education to physicians out there. I think physicians are hungry for this. If you look at ILD and what we have for some ILDs, we can treat them with immunosuppressive therapies. For the fibrotic conditions, we have nintedanib and pirfenidone. Those aren't home runs. They help. They delay disease progression, and there's data to suggest that they improve survival. The analogy that I think about with all these different things and dealing with patients with various advanced forms of lung disease is we put various scaffolds in place to catch patients. We put them on oxygen, we put them on antibiotics, we put them into pulmonary rehab. This is another scaffold further down that we can help to catch patients and delay their disease course. I think, because these patients are on the more severe end of the spectrum, and these are patients that have been typically neglected in the clinical trials, I think my viewpoint is that there should be good uptake of the medication, both by physicians as well as patients who are prescribed it. I apologize, I can only take one question at a time, and I forget if I addressed everything you asked. I think there was another aspect to your question. Oh, yes. I was just on mute. The last question is: When patients get on the drug, what will be the compliance rate? If we think about next three years. Yeah. I think that compliance in this patient population will be quite good. That's my anticipation. Sometimes there can be cough and a little bit of intolerance. You saw that some patients settled out at a lower dose, but they still, despite the lower dose, they did better. I think patients who are symptomatic with lung disease tend to be quite motivated. I'm anticipating that compliance will be very good. If you look at, say, IPF clinical trials, where you have very mild patients, and you have to talk them into taking an antibiotic, that can sometimes be difficult because they say, "Well, doc, I'm feeling okay. Why should I take this medication?" These patients aren't feeling okay. They're all symptomatic. Their walk distances are 260. They want to be able to do more. I anticipate that compliance should be good, especially if the medication makes them feel better and do more, that's just going to enhance the compliance. That's been my experience. I have a question for Michael. When you guys are targeting ILD specialists, how aware are they of pulmonary hypertension, and what percent of ILD specialists that you are going to be targeting are currently actively diagnosing pulmonary hypertension? I don't have exact percent it is. I would say they're generally aware of pulmonary hypertension. I think the diagnosis rate and the treatment rate is extremely low. That's what we have been trying to address since, frankly, last fall, and we'll continue to address between now and launch and then beyond. I think as Dr. Nathan alluded to, it's really going to be a process of continuing to educate these physicians about how to screen and diagnose these patients so that they can get the treatment they need. Thanks, Michael, and thanks, Eun. Our next question will come from Jessica Fye from JPMorgan. Great. Thanks, guys. Maybe similar to Eun's question, just trying to hone in on the kind of addressable population here. What proportion of the PH-ILD population resembles the study population, given some of the comments made, I think, by Dr. Nathan, that the patients tend to be more sick than in PH studies? I think the inclusion criteria cast a pretty wide net in terms of the diseases that were included, and pretty much anything they needed was to have Right Heart Cath proven pulmonary hypertension to get into the clinical trial. I think it is reflective of the population out there. I think the question that we'll all have to ask, and which I ask myself every day, is when do you do the Right Heart Cath? What if you do the Right Heart Cath and the PVR is 2.8 and the mean PA pressure is 24? We know that this tends to be progressive over time. The concept will be to do more Right Heart Caths, but sometimes we might not be able to show or document pulmonary hypertension. It might only manifest six months later or 12 months later. That's what we're going to have to be prepared for as well. Okay. Is the 30,000 patient estimate an estimate of those who have a confirmed PH diagnosis per Right Heart Cath? Yes. I think that that's going to be conservative at the end of the day. I think we're seeing more ILD. If you look at those numbers in terms of the incidence and prevalence starting out at 15% and going as high as 85%, it seems like it's almost invariable depending on when you look for it in the patient's clinical course, you're going to find it. Unless something else gets these patients, and some of them are elderly and some of them might succumb for other reasons, many of them will develop pulmonary hypertension at some point in their course. It's actually interesting, this paradigm between PH docs and ILD docs. PH docs are either cardiologists or pulmonologists. ILD docs are all pulmonologists. The cardiologists are not that aware of ILD, but now they'll have to be. I think where we're going to find these patients are in the ILD clinics. That's where they're going to present first. I think that's where the education's going to become very important. It's very rare that someone will get sent to a cardiologist for pulmonary hypertension. The cardiologist says, "Aha, well, you have interstitial lung disease, and that's why I have pulmonary hypertension." That's extremely rare. It's going to be the ILD docs. I think as soon as you have a treatment to offer these patients with more advanced disease, I think the education's not going to be that difficult, in terms of at least convincing them to go the next step and get a right heart cath. A Right Heart Cath these days is kind of bread and butter for any cardiologist. It's a same-day procedure. It's not a huge procedure with a lot of morbidity or mortality. What's interesting to me, this is a question I posed to some of my ILD colleagues: would you much rather send the patient for a biopsy or Right Heart Cath? Which one is going to help more? Arguably, the Right Heart Cath would help more in many of these cases, rather than subjecting them to a surgical lung biopsy to get a tissue diagnosis. Okay, got it. Maybe just the last one, you've kind of talked about how these patients have very symptomatic, disease, and clearly there's a benefit for the drug here on a number of these disease measures. The paper does say that there was no significant between-group difference in patient-reported quality of life. How do you reconcile that, I guess? Ultimately, I guess, what does it mean commercially, right? Yeah. I think that's an important point. The first thing I'd say is that if you look at the antifibrotics in interstitial lung disease, none of them have been shown to impact quality of life. If you look at the pivotal pirfenidone and nintedanib studies, those were 52 weeks, much longer, and there was no measure of a PRO difference. Quite honestly, I think the St. George's Respiratory Questionnaire is not the best questionnaire for this patient population. I think we need better instruments, and it is difficult to show a difference in quality of life metrics over a 16-week study. If you look at some of the questions that St. George's gets to, it says something to the effect, I don't remember, I haven't looked at it in a while. How do you feel now compared to, say, two weeks ago? Something like that. Some of the questions go to wheeze and cough, which might not be relevant in patients with ILD. In terms of disease-specific questions, I think the St. George's, which was initially designed for the COPD population, is not the best instrument to be using in these patients. I think sometimes when you have short to intermediate studies, like this one was, I call it intermediate, 16 weeks, it doesn't fully capture the benefit of the drug that we might see over time. The analogy I'll use, and I'm not going to speculate too much, but if you look at the antifibrotics that showed a difference in FVC at 52 weeks, well, now we're seeing that patients on antifibrotic therapies are living much longer. We can't do the three or five-year study to show that difference. It wouldn't be feasible. If you look at some of the drugs that were approved initially for PAH, bosentan, ambrisentan, and tadalafil, those were 12 or 16-week studies as well. What was the primary? The six-minute walk. What we know now is that patients with PAH are living significantly longer. I'd put REMODULIN into that category as well. I think the original treprostinil study showed a difference in the six-minute walk of 14 meters. There was a lot of controversy when Subcu REMODULIN first got approved. Clearly, the benefits of Subcu REMODULIN, IV REMODULIN are far superior to what we saw with those relatively initial short-term studies. I'm being a little bit speculative in this regard, but to the point that sometimes what we see in the context of a clinical trial doesn't fully capture the long-term benefits down the road. Thanks, Jess, and thanks, Dr. Nathan. Our next question, Josh, it will come from the six-four-six number. That's Jason Zemansky with Bank of America. Jason, you can hit star six to unmute there. Hi, team. Can you hear me now? Yes. Perfect. Thanks so much. Jason Zemansky with Geoff Meacham's team. Congratulations on the study. I was curious, is there a breakdown of the results based on disease severity? Were the outcomes more concentrated on those with more severe disease, or did you see the effect on the earlier stage patients, maybe those with an mPAP closer to 25 millimeters of mercury? I think that now that the primary paper's been accepted and published in the New England Journal, that's one of the spinoff papers that we are actively going to be working on, is looking at the different subgroups. Expect that hopefully to come out in, I don't know, it depends on how quickly we can get that together. I think that if you might remember that forest plot I showed along the way, there did appear to be a bigger difference in the patients with a higher PVR. I think I wouldn't speculate too much around that because that wasn't subjected to a multivariate analysis to know if there were more patients with IPF and IIPs in that group that showed the greater benefit. What I can say is a cursory look at the various subgroups doesn't appear that there's one distinct subgroup that didn't necessarily have a response. I think that those forest plots I showed you, everything was at least on the line or to the right of that line, suggesting a favorable benefit. Now we're going to do a deeper dive into the subgroups to see if we can glean more from there. Thank you. That's very helpful. One of the limitations of the study, at least mentioned in the paper, was approximately 21% of those enrolled didn't complete the course. If they're an earlier stage patient, what's the likelihood for a longer duration of therapy? I think that there were patients who dropped out, but the caveat there is that this is a sick group of patients, and the dropout rate was very equivalent between the placebo and the treatment arm. There might be some criticism of, well, this was only a 16-week study. Well, that's a problem when you're enrolling a sick group of patients. How do you keep these patients in a study for a longer period of time? I think that 16 weeks was right on the mark, otherwise you would have risked potentially having more dropouts and not seeing the positive benefit that we did. To your point, we only studied patients once they had documented pulmonary hypertension. Could we have more benefit if we get them beforehand? Now, that wasn't the study design and probably won't be in the label. To me, that's something that perhaps makes intuitive sense. If someone's mean PA pressure is 24, do you deny them therapy and wait for it to be 26 before you put them on therapy? This is something we're going to have to wrestle with as we move forward. Got you. Thank you so much for the color. Really appreciate it. Thanks, Jason. Our last question is a write-in question for Dr. Nathan. "Could you share your thoughts on how important the dry powder inhaler version of TYVASO will be for adoption? Do you expect it to increase the willingness of ILD docs to manage TYVASO patients themselves?" I think that's really exciting, and I was excited to hear that apparently, if you guys or when UT gets approval for this, that it will extend beyond PH and will apply to this patient population as well. I haven't seen the device myself. You guys probably can give further insight into that, but I understand that it's like a metered dose inhaler that you can put it in your pocket. Is that it right there? I can barely see it. yeah. I think it makes a huge difference to patients. It's like an albuterol inhaler. You put it in your pocket and you walk around with it, and to use it four times a day becomes much less cumbersome, to be quite honest, and is much more conducive to quality of life, getting out and going to the shops and hopefully we can all go to the shops again post-COVID at some point. Going to wherever you're going to go and socially distance and get out your little inhaler and give yourself a hit of it during those times, four times a day. When is that? It's when you wake up, at lunchtime, early evening, and bedtime. Just makes it so much easier, and I think the adoption will be so much better. If this therapy hasn't been adopted beforehand, I think it's going to be very good and very nice and convenient for the patients. Well, thank you so much, Dr. Nathan, and thank you to the UT team for taking the time to share our thoughts on the INCREASE trial. We're looking forward to speaking with everyone again at our fourth quarter earnings call at the end of February. In the meantime, if you have any questions, feel free to reach out to me, DSteadman@unither.com. Also slides from today's presentation are available now on our website at ir.unither.com under the Events and Presentations tab. Once again, thank you for joining us and have a great afternoon or evening.