Hi, Jess. How are you? Happy New Year. Happy New Year to you too. Congratulations on the baby. Thank you. Thank you. Thank you. Great. Good afternoon, everyone. My name's Jessica Fye, a large-cap biotech analyst at J.P. Morgan, and we're continuing the 44th Annual J.P. Morgan Healthcare Conference today with United Therapeutics. I'm joined up here by the company's Chair and CEO, Dr. Martine Rothblatt, who's going to give a presentation on the business. Then we're going to go into some Q&A. If you're in the room and you want to ask a question, just raise your hand. Someone will bring you a microphone, and if you are listening online, you can submit questions to the portal, and I will read them off up here, so with that, let me turn it over to Martine. Thank you, Jess. Thanks, Jess. And thanks, everybody at J.P. Morgan, for coming to the presentation. I'm going to show quite a few slides today and say a lot of words. But I think if you leave here with just two words, you will understand United Therapeutics completely. And those two words are IPF. That's one word, IPF. And the second word is super-prostacyclin. That too is just one word, hyphenated, super-prostacyclin. And I think if you just come away with those two words, you will understand the amazing potential that United Therapeutics has. Now, what do those two words mean? IPF is an acronym for idiopathic pulmonary fibrosis. And this is a fatal condition that robs patients of their ability to breathe. This IPF indication has been known to medicine for many, many decades. In all that time, there have just been two medicines widely approved for that condition. One new medicine just recently approved in a couple of jurisdictions. None of those three medicines has made any truly significant impact on the progression of pulmonary fibrosis. In fact, several years ago, when I tried to purchase for United Therapeutics, the company promoting one of those two medicines, a company called InterMune, our scientific advisory board unanimously told me not to purchase the medicine because, in their experience, it had had such a de minimis effect on their patients with pulmonary fibrosis. That company ended up being able to make a pretty good chunk of revenues with that product. The scientific advisory board's opinion, which was full of KOL pulmonologists, was what it was. The other word is super-prostacyclin. What does that mean? Prostacyclin is an endogenous molecule, meaning it's a molecule that's made based on coding in your DNA and is absolutely essential to life. It keeps all of a person's blood vessels patent and open and free of sticky platelets, among other things, some of which science is just beginning to learn. So, oh, some like 30 or so years ago, a Nobel Prize was granted to the chairman of our scientific advisory board, Sir John Vane, for discovering the mechanisms of action behind prostacyclin and other drugs that act on or downstream of phospholipids. And then that same Sir John Vane, in his laboratories at Burroughs Wellcome, was able to develop a stable analog, meaning an artificial kind of tweaked version of that prostacyclin molecule. And that molecule ultimately became the bedrock of United Therapeutics. And we have turned that molecule into a number of lifesaving medicines for patients. They go by the names of Remodulin, Tyvaso, Orenitram, and other companies as well have developed this treprostinil molecule into good medicines for patients. There have also been other variants of the prostacyclin molecule or the prostacyclin pathway that have been developed by other companies. These have all also been shown to be of benefit to patients with pulmonary hypertension. However, all of these various analogs of the endogenous molecule, and certainly the endogenous molecule itself, have severe therapeutic, pharmacokinetic, and pharmacodynamic limitations that don't allow them to reach the full potential of being able to give the patients the full measure of health that would be possible from modulating the prostacyclin pathway. We at United Therapeutics have developed a next-generation prostacyclin molecule called ralinepag, which is what I call a super-prostacyclin because it has the best and by far the only truly long-lasting pharmacokinetic life. It has the most potent pharmacodynamic effect on the prostacyclin receptor pathways. And even though we will just unblind the phase 3 trial within the next three months, it has also shown in open-label extension data from patients from that trial a physiologic effect which is above and beyond anything that we have seen with any other of all of these 30 years of molecules in prostacyclin. So IPF, click. Superprostacyclin, click. You've got United Therapeutics' story for the next several years. We have been able to reach this threshold of developing what I believe will become quickly recognized as the best product for IPF, or pulmonary fibrosis, as a result of a trial that we unblinded just, oh, I guess it was about three months ago now, called the TETON 2 trial. And this trial of inhaled Tyvaso, one of our medicines, in patients with IPF, both patients with IPF who were on these don't-work-so-good therapies that I mentioned earlier, or on no background therapy at all, had such a dramatic improvement in their forced vital capacity, which is the widely accepted measure of how well patients with pulmonary fibrosis are doing, that every single physician we have spoken to, key opinion leaders, everybody has said, "This is a game changer in pulmonary fibrosis," and feel extremely confident that this will become the most prescribed medicine in IPF. Now, just a word about IPF. Over all of these years that you see on this chart, we have received not $1 of revenue, no growth in patients, nothing from IPF. Yet it is an indication with, just in the United States alone, a prevalence of about 100,000 patients. And most of them, unfortunately, die in just a handful of years. So I believe that we will quickly make this kind of revenue course that you see on this chart completely irrelevant by ramping Tyvaso into this completely virgin 100,000-patient population where the data shows it is above and beyond far better than any of the medicines currently approved in that indication. The other interesting thing to look at this chart of over these past many years, you see this continued growth. All of this is with the first-generation, somewhat problematic prostacyclins, prostacyclin analogs, prostacyclin receptor antagonists that have been out there in the market. This is the kind of revenues United Therapeutics have been able to do. All of this past revenue growth, I think, is truly irrelevant because the vast majority of all of these patients, as well as all of the patients who are not in our medicines, are going to migrate over to this super-prostacyclin, which is much simpler to take, just one pill a day, much more effective in the prostacyclin receptor pathway, and, as I mentioned, has already shown physiologic benefits which are better than anything else we've ever seen before. Now, we will unblind that trial, as mentioned, just in the next three months, so you're not going to have to wait very long to see it, and assuming that the data are positive, which I'll show you a little inkling in a moment what those data might look like, then you will see us filing for approval this summer, hopefully approval from the FDA next year. And then this type of 20-year history that's shown on the chart here would really just be the starting point for a takeoff in revenues that would be two, three, maybe even four times the level that you see here in this chart. We at United Therapeutics have done so much to make the most out of what we have. Here's an example of how difficult the current generations of prostacyclins are. They are so hard to manage that this patient here has to take the prostacyclin by an infused delivery 24 hours a day, 365 days a year, with no interruption. With this new super-prostacyclin that we'll be introducing, this entire delivery system can be replaced with just one pill once a day and greater affinity within the prostacyclin receptors that line the pulmonary vasculature and airways in the lung. So it's going to be a game changer. And when people talk about what made United Therapeutics of 2026 to the 2030s so much different than what happened before, they're going to say one word is going to be the super-prostacyclin, Ralinepag, and the other word will be they have become the go-to drug in IPF. United Therapeutics, even though we are focused on these two words and the two words I want you to keep in mind, it's not that we don't also concentrate on other indications. And this is where I think a lot of our business development growth will be coming. We always have kind of a philosophy of to do our best to leave no patient behind. In this chart, you see the logos of a couple of our products that are addressed to orphan populations. The one on the right is the one I'll speak to for a moment here while we talk about business development. This drug, Unituxin, is approved by the FDA and by the regulatory authorities in other jurisdictions for the treatment of neuroblastoma. Neuroblastoma is an almost universally fatal pediatric cancer of the nervous system. But after Unituxin was approved, and for those patients to whom it was given, half of the patients completely vanquished their neuroblastoma and have gone on to live a normal life with no recurrence of their cancer, even five and more years after the cancer was first diagnosed, a true cure for these patients with neuroblastoma. So we've now built up this indication into a position of leadership among pediatric oncology centers. And when people ask me, "Martine, I understand about IPF, you're going to crush that. I understand about the super-prostacyclin, you're going to be the go-to drug. What are you doing in new business development? This orphan oncology area is one of the key areas that we're looking at for new business development to try to leverage our success with neuroblastoma into other pediatric and orphan cancers. Now, the Tyvaso drug, which proved itself to be so remarkably successful in IPF, and it's very interesting that we had run our phase three trial in a very detailed computational biology model, an AI model of the human lung that we've spent the past five years developing at United Therapeutics. We call it the CLIME model, CLIME being an acronym for computational laboratory for in silico molecular biology. In other words, instead of running trials in vivo, you can run them in silico if you accurately model all the aspects of the in vivo entity, which we have with regard to the lung, and when we did an unblinding of our in silico model of pulmonary fibrosis with the Tyvaso drug that you see here, we came up with a measure of its efficacy in terms of its improvement in forced vital capacity. Again, the main measure that was within 30 milliliters of oxygen of the actual in vivo pivotal trial that we later unblinded, but what's really fascinating is the unblinded data was about 60 milliliters of oxygen better than the other competitive drugs that are out there in the market, so this is to say that our in silico models are pretty damn good. Even if the FDA had approved something based on the in silico model, which I think will start happening within the next decade or so, it would have been far better than the drugs that are already out there. But nevertheless, we did prove it in the in vivo model. By the way, for those geeks of you who are in the audience, it took us three years to conduct the in vivo model in hundreds of patients with pulmonary hypertension. We ran 54 pivotal trials of the in silico model in just 48 hours. Imagine a future when you can run so many clinical trials in such a fast period of time and get such accurate results as we got for pulmonary fibrosis. This chart shows a next-generation Tyvaso device that we do at UT. One of our core competencies at UT is something that we call drug-device combination products, and this is where we combine a drug with a device to make the drug do something much better than it could do without the device. And it also adds a lot of proprietary IP to the drug, which allows us to reinvest and develop yet better drug-device combinations. I'm looking over here at one of the heads of the United Therapeutics Skunk Works, where Pat Poisson has about a dozen different advanced devices like this. He's a genius, and his team is a genius at turning our molecules into effectively brand new pharmacokinetic and even pharmacodynamic properties of drugs based on their passage through these unique types of delivery devices. That's something that is right now, in fact, our best-selling drug in the United States for pulmonary hypertension. I think you're going to see this in IPF as well. In terms of pulmonary hypertension, I think it is going to be overtaken by the super-prostacyclin, Ralinepag, that I referred to earlier in terms of our best-selling drug. But we never mind lapping ourselves to create better healthcare for patients. I think that's what it's all about. Here you see an example of why Tyvaso DPI works so well. Compared to other types of devices, it reaches much further into the distal portions of the lung. For those of you who are well-versed in pulmonary biology, you probably know that the lung is a branching structure. It's like two, four, eight, 16, 32, and you know very quickly you get up into the millions of tiny, tiny arterioles. It's in those far distal portions, meaning the tiny, tiny ones that may be like 10 millimeters in diameter, micrometers in diameter, sorry, about 10 micrometers in diameter, that the pulmonary hypertension takes hold, so you need a drug that can get down to the far distal portions, which the Tyvaso DPI does. That device does it far better than any other product out there, and no doubt that's why it's far and away the best-selling DPI type of device. Now, I mentioned to you that when you take Tyvaso into pulmonary fibrosis, you get dramatically better results than have ever been seen before, and here you see the data from the, what I promised you to take a peek at from TETON 2. This is the unblinded data from the TETON 2 trial, which was completed in the fourth quarter of last year. You can see that the patients on drug did far better, 0.0001 p-value than the patients who are on placebo. We are now completing a confirmatory study. In fact, it's fully enrolled. It will be unblinded in the first half of this year, so sometime in the next two, three, four, five months. We expect that trial that's called the TETON 1 trial, we expect that trial to pretty much overlay with this data. Certainly, our computational model implies it would overlay with this data. That'll be amazing because then we'll submit it for approval. I think the FDA will be very, very excited to grant it approval. Finally, for the 100,000 patients literally suffering to death from pulmonary fibrosis, there will be like a life raft, a lifeboat that they can jump onto, which will be Tyvaso. It should definitely, at minimum, greatly improve their quality of life, improve their oxygen saturation, which will logically improve their longevity of life as well. Super, super excited about this. We have every reason to expect that we should be able to garner onto this drug literally tens of thousands of brand new patients within the two, three, four years after it's launched. We have been building up our inventory of Tyvaso inhalers so that we have an adequate supply of drugs and devices to stay on top of literally a hockey stick launch into the IPF indication. I also promised you a sneak peek at the super-prostacyclin, Ralinepag. Here you see some data. This trial, again, is still blinded. We won't see the unblinded data until the next, oh, two or three months from now. So it's very exciting, two major news events in the same year. Neither of them terribly risky, very largely de-risked by now. But here you see that the Ralinepag and the open-label extension study, all of this little data might not be visible to everybody in the back of the room. But basically, what it shows is that for the people who left the drug in the open-label extensions phase and then went on to the drug itself, their improvement in their six-minute walk continued dramatically and was maintained out to two years here with an improvement level of just about 40 meters of six-minute walk distance, which you almost never see in any of the first-generation prostacyclin drugs. So this is the beauty of our pharmaceutical industries. We can do these next-generation drugs and have kind of step function improvements in the exercise performance and the physiological health of the patients we treat. So again, this kind of open-label extension data very largely de-risked this product. And we believe that it will become the most prescribed medicine for pulmonary hypertension. Right now, there's about 50,000 patients in the U.S. with some form or another of a drug prescribed for their pulmonary hypertension, most often a drug called a PDE5 inhibitor. For those of you who are familiar with that class of drugs, they go by for an ED, they're called Cialis or Viagra. In PAH, they're known as Revatio or Cialis. We ourselves have had an amazing partnership with Lilly over about 15 years now. Lilly chose us above all of the other companies working in pulmonary hypertension to entrust Cialis to us and have been exceedingly pleased with the results, so we treasure our partnership with Lilly and under our stewardship, that drug became the most prescribed drug for pulmonary hypertension. Now, our drugs, which are also very good and great drugs and have been fantastic for UT, as you saw in the revenue steps at the beginning of my talk, our drugs have reached about 15,000 patients, which let's say is around a third of all the U.S. patients with pulmonary hypertension. Ralinepag, mark my words, we are going to go past 15,000, okay, and we're going to become the most prescribed drug of this category for pulmonary hypertension. That will just be humongous because if you combine this potency of a super-prostacyclin with the known functionality and safety profile of a PDE5 inhibitor like Cialis, everybody accepts that is safe, and an ERA, which is another type of generic drug which is out there, you have a triple threat. You are addressing the three predominant pathways of pulmonary hypertension. The most potent of those will be in our armamentarium, ralinepag. Then you can even overlay on top of those other drugs which have been shown to be synergistic, like a TGF inhibitor such as sotatercept. There is already very, very exciting data available that shows the synergy of sotatercept, to whom I give huge kudos to Merck for their superb work on developing that drug for pulmonary hypertension. And so happy to see patients who are on both that and prostacyclins doing even better than they would do on either one alone. It's also been somewhat in the news that United Therapeutics is trying to solve the problem for patients with pulmonary fibrosis, IPF, or pulmonary hypertension, PAH, for whom all of these drugs do not work. There are always some patients that progress through. We have shown if the patient is treated in the right way in the right expert center and they get their numbers down into a safe zone, they could get into kind of a stable equilibrium and go for decades without a need for a transplant. But not every patient is going to fall into that treatment channel, if you will. For those patients whose pulmonary pressures get out of control or whose pulmonary fibrosis gets out of control, a lung transplant is the only pathway. We began looking several years ago at xenotransplantation as a way to provide an unlimited number of lungs for these patients. What we found out is because the lungs have the largest colonization by immune cells, especially primary immune system cells such as macrophages, and these are the innate immune system, which just jump on anything right away, that we did not have success with xenotransplantation in immune cells. Since we wanted to make the best use of every pig that we had to sacrifice that we had genetically engineered to be used in humans, we tried the kidneys and the hearts. Sometimes it's like you got to do the experiment and you see the amazing results. Kidneys and hearts work great, even though the lungs didn't because of their disproportionate overload of immune cells, so we went ahead and developed our xenotransplantation platform for xeno kidneys, xeno hearts. The FDA has now approved two of our clinical trials for xeno kidneys. First, patients are already enrolled. Very modest requirements from the FDA, just something like three, four dozen patients max is all you need for FDA approval. And as I mentioned, we're already on that clinical trial pathway, so I feel pretty confident that before the end of this decade, we'll be able to complete that clinical trial, submit the data to the FDA, and obtain approval for creating an unlimited supply of transplantable kidneys and hearts from these xenotransplantation models. We've, in fact, already built two commercial and one clinical xenotransplantation facilities, one in Houston, Texas, one in Minnesota, one in Virginia. These three xenotransplantation production centers will be able to collectively provide well over 1,000 xenografts a year to patients upon FDA approval. I'll note that we also are on the cusp of submitting INDs for two more xenotransplant studies in the xeno-heart and the xeno-thymic heart. Very probably within the first half of this year, knock on wood, the FDA will increase the number of approved INDs that we have in xeno from two to four. For those of you who've been following, you feel quite amazed for a long time. It's quite amazing to imagine that here in 2026, there'll be four FDA-approved INDs for xenotransplantation. Truly amazing. We didn't forget the people with the lung problems. It's not their fault that our lungs are all full of macrophages. Probably a very good thing that they are. We decided the best solution for them would be to not insult the immune system and instead give them a cellularized lung that is matched to their own DNA or at least to their own HLA type. We do that. We manufacture the lung shape, and we do that in a number of different ways. Then we cover that lung shape with iPSC-derived cells or HLA master bank-derived cells that cover the airways of the lung and the vasculature of the lung. Then we keep them breathing in a bioreactor, test them like one would do an ex vivo lung perfusion. That's even a whole nother organ transplantation pathway that should be at the stage of FDA approval either at the end of this decade or the beginning of the next one. So all told, I think you remember the two words that I told you summarize UT, mostly because I know most of you are financialists and you care about the numbers. So the numbers are going to be overwhelming IPF and super-prostacyclin. So you remember those two words. But we do a lot more. We do exciting BD in oncology and exciting clinical development and transplantation. And I've reached a time on my clock when I need to open up the floor for questions. So thanks for your patience listening. And between myself, our President, Chief Operating Officer, Michael Benkowitz, and our Chief Financial Officer, James Edgemond, we'll be happy to answer all of the questions that you have. I urge you to ask questions because if you don't, Jess is going to ask all the questions. And her questions are much more difficult. So please ask questions. Great. Yes, sir. The inhaler, is that your IP or is it from a contract contractor source? So very good question. So the answer is both. The specific inhaler that I showed in that image is from a third-party contractor called MannKind. And they developed that inhaler for delivering insulin for diabetics. And we re-engineered it to work with Tyvaso. So that one is from a third-party contractor. We have actually almost finished building our own manufacturing plant for that inhaler, which will open up, begin producing stability batches for commercial launch by the end of this year. And then we'll commercially launch those products out of that company internal source next year. In addition to that, we have other devices that I mentioned in our skunkworks that are developed internally to UT. And there's not a lot that I could say about them right now because they are in stealth mode. I have on earnings call mentioned that I would share a lot of the details of the next-generation drug devices after we file the NDAs for the super-prostacyclin for IPF. Those NDAs will go in this summer. So if you watch this space by the third quarter of this year, you'll get more insight into the completely proprietary next-generation inhalers similar to the one I showed you. Next question. There's a roving mic there if you want your question to be heard from everywhere. Going once, going twice, going Jess. All right. We do have a question on the iPad here on the portal. So what is the latest thinking on whether you'll need two trials in IPF given the potential FDA flexibility on not needing two trials in some cases? Could you file with TETON 2 alone? So we're going to file with both of them because we're very, very close to having the TETON 1 data. The guidance that we've received from the FDA, which has been superior throughout this, special recognition would go to the pulmonary division at the FDA. So just because some parts of the FDA might do things one way and different divisions of the FDA do things a different way due to the greater complexities involved, they've guided us to do two studies in this indication. I will say they actually guided us extremely wisely. They guided us to include both patients on the background therapies that don't work very well, and they know they don't work very well, as well as patients that have given up on those background therapies. Actually, there's probably more people that have given up on those background therapies than use them because they have a very bad side effect profile associated with them. So the FDA wanted to make sure that we had data both on naive patients as well as those on background therapy, which is reflected in the IPF pivotal data that I showed you previously. So we thought about it and we said, "It's just going to be like three months until we unblind this study. Let's just go ahead and do things right." We have a few adages at UT. I try to keep them not too many. But one of the main adages is that there's always time to do things right. And I think the right way is to lead in the strongest possible way with two well-controlled pivotal studies, both demonstrating amazing results for Tyvaso in IPF. And so that's what we're going to do. And what are your expectations for the results in TETON 1 relative to TETON 2, particularly when you think about the availability of Tyvaso in the TETON 1 territories? Yeah, we think that the results in TETON 1, just for everybody to get on the same page, so it's exactly the same trial, exactly the same protocol for TETON 1 and TETON 2. TETON 1 is done in the U.S. and TETON 2 was done outside the U.S. TETON 1 started first. That's why it was called TETON 1. TETON 2 started second. For TETON 2, we had the advantage of a CRO. At the moment, I forgot this particular CRO's name. But they had just finished. They had exactly just finished doing an IPF study that unfortunately didn't turn out well for the sponsor. So they had dozens and dozens of IPF centers that were all ready up and rearing. They had patients that had to get off their previous therapy. So they were able to enroll very, very quickly. And that's why they beat TETON 1 for a few months. It is true that Tyvaso is not generally available in Europe, whereas it is generally available in the U.S. So the people sometimes have asked, "Well, are you worried that the patients who did so well in Europe in TETON 2, that some of those patients actually did not really have real IPF? They actually had pulmonary hypertension and that would be and they didn't have anything to avail themselves of." So that thing bumped your statistics. Whereas in the U.S., a patient with pulmonary hypertension would supposedly be able to definitely access Tyvaso so that you would have a "pure IPF alone population" in the U.S. versus in Europe. But in fact, there's absolutely nothing to back that up in all of the data. We have the background characteristics of both the TETON 1 and the TETON 2 population are exactly the same. We have various indirect indicators that can tell us whether or not there's any pulmonary fibrosis, any pulmonary hypertension in the TETON 2 population, which there was not. So we feel 100% confident that the background is strictly comparable. And given the hyper-strong statistics from TETON 2, we expect to have an overlap result with TETON 1. Yes, sir. Wait, they'll bring you a mic. There's a home audience that wants to hear your questions. Hi. So it's very exciting that you're going to be scaling up these xenotransplantation facilities. How are you thinking about quality control there, particularly with the risk of porcine endogenous viruses, which obviously at scale is quite a big risk if you get that wrong? Yeah, it's a very challenging undertaking to scale up a xeno product. Okay? I was in one of my one-on-ones earlier today and I said, "A xenograft is basically a product from hell with angel wings." So it's a product from hell because it is a very large biologic. It ain't no monoclonal antibody. Okay? It's just this massive biologic product that has nothing that the industry has ever manufactured before. So you have to give a humongous amount of attention to quality assurance and quality control processes and the whole GMP type of process. On the other hand, it's a product with angel wings because it is literally life-saving. Every one of those kidneys that we make is a life-saving product or a heart. So it's not a product you want to be afraid of because it's a challenge. And we've gone to the nth degree to make sure that we manage all the QA/QC aspects of it. Just to brag for a moment, not that past is prologue, but UT has been making biologic products for over 10 years in terms of the monoclonal antibodies. We've not had one single 483 from the FDA. We've been inspected numerous times and we've been making small molecules even longer and no problem with any FDA inspections. So we have a large QA/QC group. Roughly speaking, we have about one QA/QC person, for example, and not just anybody's anybody. I mean, they're highly trained and all that kind of thing for about every two to three people in manufacturing. So it's a very high overhead. We have built facilities that are designed to ensure that every product goes through superior QA/QC. I will say all of the product pigs are actually birthed inside of a designated pathogen-free facility. So it's not easy. It's extremely difficult, and what we've decided to do is, even though the need for these kidneys is very, very large, we've decided to take a modular approach in building these facilities so that we always are five steps ahead of any QA/QC scale-up issue that we might run into. So we build these facilities to handle a few hundred organs each one, and I mentioned to you that there's three. So that gives us like 1,000 a year. And we own the land adjacent to these facilities so then we can modularly add additional facilities each one of a scale that we can manage scale up with full attention to QA/QC. Last questions? No more? Martine, I guess with regard to the forced vital capacity review, you heard a 60 mL number. Can you talk about the significance of what that 60 mL delta, what it means relative to the current standard of care? Yeah. I would say it's more than double what you could see in the current standard of care. So it's quite significant. A patient would, I think, really, really appreciate it. Great. Well, we are out of time, so we will stop there. Thank you. Thank you.