All right. Well, thanks so much for joining us, everybody. I'm Terence Flynn, Morgan Stanley's U.S. pharma analyst. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. I'm very pleased to be hosting United Therapeutics this afternoon. Joining us from the company, we have Martine Rothblatt, who's the company's Chairperson and CEO, and Pat Poisson, who is EVP, Strategic Development. Thank you both so much for taking time out of your day to join us. Really appreciate it and looking forward to the conversation. Maybe Martine first, I'll just turn over to you to maybe make some framing comments before I launch into my questions. Thanks so much. Sure. Terence, thank you so much for inviting us here. We appreciate it. It's great to have the opportunity to give some framing comments because this is a very unique point. No other point is like this quarter in United Therapeutics' entire history, because this is the quarter that we have gone ahead and inflected ourselves from being an orphan drug, pulmonary hypertension company, which was our history, developing great medicines, multiple great medicines for pulmonary hypertension and building ourselves up to a few billion dollars a year in recurring revenue and inflecting ourselves into a pulmonary fibrosis company, that will be treating hundreds of thousands of patients with a best-in-class drug for idiopathic pulmonary fibrosis. We're pretty confident we'll soon show similar results in progressive pulmonary fibrosis, which is not an orphan disease. On top of all of that, due to some new products that we've developed, such as our coughless Tresmi inhaler, we'll be launching studies next year into a form of COPD called COPD-PH, which can be uniquely treated by our drug and has a prevalence in the United States of 400,000 to 800,000 patients. It's just amazing, Terence, I know you've been with us for quite a number of years, monitoring the company, to be at this point in time when you look behind you and you see, okay, you've gone from nothing to being the largest player in pulmonary hypertension, building up this several billion dollars recurring revenue, and then looking forward and saying, "Oh my God, we're about to launch into becoming like a major bracket biotech company with something like $50 billion to $100 billion in pharma revenue, mostly in non-orphan indications," all based on clinical trial results that have been now submitted to the FDA and in the estimation of all of the experts, whether in PAH for our medicine, JENRALDI®, once daily pill for pulmonary hypertension, or in IPF for our medicine, nebulized Tyvaso. In everyone's estimation, these are the best drugs in these two different diseases with the best clinical trial results that have ever been shown. It's a hell of a point to be giving you framing comments right now. Great. Appreciate the update. Again, we were talking earlier about how far the company's come. I think I've been covering the company for 20 years, but obviously a lot has changed since those days. Yeah. I pinch myself, actually, because I remember when we were five people and now 2,000 people with 14 drugs in active development. It's truly amazing. Great. Well, I think I know the answer to this question already, given your framing comments, but I think the official long-term guidance you guys have given is $8 billion in revenue. Now, again, as you just think through confidence level there, but maybe what are the drivers to get to that $8 billion before we talk about the $50 billion? Sure. The $8 billion we see coming from all of our core business where we are continuing to grow in all of our legacy products like Remodulin, Orenitram, and Tyvaso. But especially in the newly launched projects, which include, first of all, nebulized Tyvaso for IPF. We've submitted that to the FDA. We've got our PDUFA dates. We're pretty confident of launching that product in the middle of next year. That product will be launched into an indication with 100,000 prevalence in the U.S. The only alternative drug that has been shown to give an improvement over some very old, very toxic medicines is a Boehringer Ingelheim drug called JASCAYD®. We're really happy to see that medicine launched, but our medicine, nebulized Tyvaso, showed in two separate phase III well-controlled studies, dramatically greater improvement than JASCAYD®. When you break it down to how many years of life an average patient can expect, they would be able to expect multiple years more of life on nebulized Tyvaso than on any other product in the IPF space. So, we certainly expect several of those billions of dollars a year to grow in IPF. In the meantime, Terence, we just fully enrolled another study in a much larger indication called PPF, and we fully enrolled this study, 700 patients. We'll have data about this time next year, and we feel very confident that our drug will work in that indication as well. When you look at the combination of 100,000 patients in IPF, 300,000 patients in PPF, that's 400,000 patients, and that will take you far beyond the $8 billion revenue run to what we expect will be in the fibrotic-type conditions like this a $40 billion pharma revenue. That's the near term. As I mentioned briefly in the framing remarks, I'll just touch on very quickly. Other products that we are developing for the IPF market, including Tyvaso DPI, and Tresmi, and then once-daily Roledpi, we will be bringing those products in to further solidify our hold on the IPF and PPF market. So, $40 billion is, it's of course a lot of money, but we have a straight shot at it. We have the clinical trial data for the base of it. I should mention that the company has been able to successfully garner intellectual property protection for its fibrotic applications of its medicines out to the 2040s, and composition of matter, IP protection for ralinepag also to the 2040s. Great. Maybe we will unpack a little bit of that on the Tyvaso for IPF front first. Again, maybe just speak to about the confidence in an FDA approval here. Again, if there is any outstanding issues or questions that FDA has raised at this point. I know it is still early in the review process. Well, super great question, Terence, but actually I can say, having looked at the FDA's comments letter, I cannot remember any letter back to us on a filing from the FDA in the past 20 years with fewer comments. So, it is not surprising that it would be a very clean situation because the FDA has been approving Tyvaso in various indications for quite a few years, for over 10 years. So, it is known to be a very safe and effective molecule. Also, the device that we are asking the FDA to approve it for in pulmonary fibrosis, the nebulizer device, is a device that the FDA has previously approved and has an excellent track record. Last but not least, the pulmonary division of the FDA asked us to do two separate trials in standalone IPF without any confounding patients from PPF. We said definitely, yes, sir, and we executed those. Wow, the results were mind-blowing. I am talking about round numbers, 100 milliliters of oxygen improvement compared to baseline, and that is way beyond anything that nintedanib, pirfenidone, or even JASCAYD® ever showed. So, I am super excited. Everybody at UT is super excited that we are going to be able to literally promise tens of thousands of patients with pulmonary fibrosis more years of good quality and good quality life, and that is a beautiful thing to do in this industry. Great. Maybe talk to us about the launch preparation. You guys have, I know, expanded your ILD Tyvaso sales force. Is it possible that you can leverage some of that existing build, or do you need another build out here to push further into the community pulmonology setting? Maybe just talk about the prep you're doing on the launch front for a second. Yeah, Terence, that's a fun question because I can answer yes and yes, which is the best. So, yes, very definitely, we will be leveraging the new hires. We doubled our ILD sales force, and a goodly number of those people in the doubled force already have a great deal of expertise in IPF. So, when we're ready to launch the product, they now will have familiarity with how to submit expense reports in the UT system and all that kind of normal and customary stuff. And we'll be able to flip over to detailing full-on, straight-up IPF prescribing doctors. In addition to that, to be able to satisfy a 100,000-patient market, we're going to be doubling that sales force multiple times. And I expect that at the rate of our product introductions into IPF, into PPF, that you'll be hearing from Michael Benkowitz, our head of commercialization, our president, that there'll be another doubling of our sales force just focused on IPF each year for the next two, three years. Okay. So, doubling every two to three years. Yes. That will cover, though, the PPF indication as well? I think that's just for the IPF. That's just IPF. Okay. Then there'll be yet additional hiring for PPF. PPF is a form of pulmonary fibrosis caused by an array of kind of other conditions and/or causes, and it's three times larger than the IPF indication. So that takes us up to the 400,000 patients, and I feel pretty confident just thinking a little bit on the fly here up on the stage, that to adequately cover the entire 400,000 patients, you would need upwards of at minimum a 1,000-person sales force, which UT, fortunately, we've built up all these different sales forces. We're good at that, and we're committed to leave no pulmonary fibrosis patient behind. Okay, great. You talked about the patient prevalence numbers already. I guess the other one is just how to think about treatment duration here for Tyvaso and IPF relative to PAH or maybe even current IPF drugs. I know the current drugs struggle with some of the tolerability issues. Their TKIs have a lot of GI side effects, among other things. How do you think about the treatment duration here for your product in IPF specifically? Yeah, thanks, Terence. We actually kind of pre-thought about the therapy duration in these patients. That is why we have queued up a line of four products that can basically address ever greater arrays of patients. People are diverse, and some people can tolerate a product, even the ones with GI side effects, for a longer time. Other people cannot. The first product introduced is a nebulized Tyvaso, and then coming on the heels of that, we have the Tyvaso DPI, which is already approved by the FDA in ILD and PH, as you know. That product is a lot easier because it is a shorter number of inhalations, more rapidly get it accomplished, you can put it in your pocket, more portable. That will be the next product introduced in the indication. Then to yet further reduce people dropping off therapy, we will next introduce this coughless Tresmi product, which is a soft mist inhaler. As the name implies, for those patients who have difficulty tolerating dry powder, which is not most patients, but a significant number. As I said, we do not want to leave any patient behind. We will then introduce the soft mist powder inhaler into the market, and I think that will yet further keep patients on the drug, reduce the number of dropouts. The fourth of these is the once daily Ralpi product with what we believe is the most effective treprostinil-like agent, ralinepag, into this indication that you only have to take one inhalation once a day. Beyond the doubt, the easiest one of all of them to stay on. Dropouts in our other ralinepag studies were very low. Between those four products, my hope is it could be just de minimis, single digits percent of patients drop off these therapies. More important than that is keeping the patients alive for much longer than was ever the case with previous drugs. Yep. When do you think you would have some survival data? You mentioned keeping patients alive. I know these trials in IPF weren't designed for that, they're lung function endpoints. But similar with PAH, we saw the field evolve from, again, six-minute walk distance to now you have longer-term outcomes. When do you think you could see some of that longer-term outcome data for Tyvaso and IPF? Well, a lot of that data you can actually get right now just using arithmetic. Pat, if I might be able to ask you Yeah, sure. to explain the differences there. Yeah. If you look at decline in FVC on a patient who is not being treated, typically you would see between 200 ml and 250 ml annually. JASCAYD® showed a vast improvement. They are down to, say, 100 to 125 ml. If you think about years, that extends that time period by a year. When you look at TYVASO, which was down in the 40 to 50 range when compared to someone not on treatment, that is a five-year change in decline. Contrasted with a healthy person where you would see 25 ml. So, you are seeing a difference really just of 20 ml from a sick patient with IPF on TYVASO, which is very close. So there is a drastic difference in clinical efficacy. Very compelling. Yeah. Okay, great. You mentioned PPF here, and you are going to have some data second half of 2027. Maybe just talk to us about why you are confident that the IPF data will translate to PPF. I know you guys have a lot of models you use for the IPF in terms of running scenarios and things like that, but where does the confidence level come from? Is it similar biology, different biology? Then I have a couple of follow-ups. Sure. With regard to the PPF, our confidence was first built up from our phase II equivalent study, which we call the INCREASE Study that we did in ILD patients that had a mixed population of some IPF and some PPF. We saw the drug was quite effective in those patients with PPF. In fact, based on that study, we went to the FDA and asked them if we could do a single combined study of IPF and PPF. The FDA pushed back and they said, "This is a new drug and a new indication, and we want to get as clear a read as possible of everything. Notwithstanding the favorable phase II equivalent data, we want you to do a separate IPF study. In fact, we want you to do two well-controlled IPF studies." Which we did, and those are called the TETON-1 and TETON-2 studies, and they produced the remarkable results that Pat just described. Then we went back to the FDA and we said, "Okay, we have got TETON-1 and TETON-2 underway. We would like to do a PPF study." By now, I think the FDA was becoming quite comfortable and familiar with the device, the drug, the use and the indication, and they agreed that we could just do a single PPF study of 700 patients. While we were enrolling the study, we received constant incoming from all the IPF docs saying, "You guys have got to develop this drug for PPF." There is nobody that really knows their patients better than the physicians treating them. Whether it was in Europe or the U.S., across the board, IPF docs were saying, "Please develop this for PPF." We did that, and Terrence, the remarkable result was that we had the fastest enrollment of a clinical trial study ever in our 20-year history, all the way up to 700. Fully enrolled now, and we'll have the data next year. I might add that in answer to your question, we've also run all manner of in vitro cell activity, cell studies to test the efficacy of the treprostinil molecule against fibrotic tissues, and whether the tissues are sourced from IPF or PPF, you repeatedly see the treprostinil is effective. Okay, great. Before we go on to some of the other products, I just want to touch on Tyvaso in-market. ILD has been the newer indication in terms of the forward. PAH was the first indication, ILD is the second. Maybe just give us an update on where you stand as of the second quarter and how to think about the outlook for that franchise on market into the second half of this year. Sure. I think we're going to continue growing in the ILD market, PH market. We are already the most prescribed drug in that market. As you may have heard on our last earnings call, we now have record starts, new patient starts in that market. The availability of both the nebulized Tyvaso as well as the DPI gives you kind of two shots on goal. Getting back to your question earlier about patient dropouts, when there's different ways for the patient to take the drug and different ways for them to reach different levels of concentration of the drug, it helps you build the patient census up. I expect us to continue growing in the market. What's changed is the indication itself, which once seemed kind of significant at, I don't know, 20,000 or 30,000 patients. After we unblinded the TETON-1, the TETON-2 results and saw the rapid enrollment in PPF, it's like, oh my God, this is not even one-tenth of the market for United Therapeutics products. This is actually like one-twentieth of it. The company's focus has very much shifted to pulmonary fibrosis and progressive pulmonary fibrosis because that market is literally 20 times as large as the ILD market. Our nature as a company is to continue to pay attention to these orphan indications. You may recall, Terrence, that we continue to serve the ultra-orphan neuroblastoma market with Unituxin, in which we save 500 kids' lives every year after year, from a cancer which would otherwise kill them. So we're dedicated to maintaining our presence in the ILD market. I'm sure we'll remain the number one seller in the ILD market, but it has become a kind of a small thing in the overall landscape of UT. Okay. Maybe just pivoting over, you mentioned your Tresmi or soft mist program already. Yep. Maybe just remind us there the target profile, and then what's getting to the NDA filing here? Sure. Maybe a good opportunity. Pat's in charge of product development and future product development. So Pat, if you could talk about that. Yeah. We're planning to file an NDA for that by the end of the year, and that NDA will be for the PAH and PH-ILD indications. Once that's accepted, I think we'll be far enough along in the IPF review where we can engage with FDA on what's needed for a bridging study to get the SMI approved for IPF as well. We intend to do the same for PPF once PPF is filed. Okay. Just remind us of the target- By the way, just not to interrupt you, Terence, but just to add one more link onto Pat's chain is with that filing of the Tresmi device at the end of this year, we can then go ahead and launch into the clinical trials of PH-COPD, which is the largest of all of our indications with 600,000 patients and roughly a $60 billion TAM. If we can capture even half of that TAM, which it would be the first and only product approved in that indication, that would take us north of the $50 billion in pharma revenue we expect over the next few years. Okay, great. Maybe just remind us, I know you said coughless, but again, anything else about the target profile that we need to keep in mind for Tresmi? Yeah, I think the big thing is really beyond that convenience in that you will be able to inhale multiple breaths equivalent to the nebulizer in one breath. Yep. Much like we did with DPI, where we started with a series of strengths and expanded that, we will do the same with SMI. And that is an internal device that you guys developed too as well? It is a partnership. It's a partnership. Have you disclosed who the partner is on that? No, we haven't. Okay. The IP on that device goes out how far you said? There's both IP and trade secrets. Okay. It's a fairly complicated device to manufacture. Okay. Martine, you mentioned PH-COPD, so maybe just elaborate a little bit there on the biology and why you guys decided to pursue that indication. Sure. We were originally led to this one also by physicians. I guess that's kind of a trend at UT is it's the physicians lead the way. So, we listen to them. One of the great physicians in this field of treating PH-COPD is Dr. Aaron over in the Boston area. He had basically off-label and investigator-initiated studies, used our nebulized Tyvaso in his PH-COPD patients, found remarkable improvement, and encouraged us to do a study, which we started in the beginning of 2020. That was called the PERFECT study. Little did we know that that was the same time COVID started. So it was some bad luck there and- Not perfect timing. It was an imperfect study timing for a kind of perfectly named trial. Enrollment was all but impossible during COVID, so it went year after year. We had to invent some things on the fly. Our patients could not go into the hospitals to do their endpoint measurements, so we had to invent equivalent endpoint measurements that they could do at their house. As you know, the company's CEO, I made a difficult decision because I know that there's a lot of these people and they need this drug. I made the difficult decision to cancel that study, just about at the end of COVID, because it was very hard to enroll it. I was nervous that these non-validated measurements, in lieu of regular hospital measurements, would result in too wide a variability of data and might fail the study, and I didn't want that. So, I stopped the study, but I decided I'm not going to stop the indication. It was about that time that we began working on our soft mist inhaler, which would give us a much better inhalation device for this patient population. We also, in parallel, ramped up our efforts into other inhaled avenues such as ILD and IPF. Now we are at the point that, as Pat said, we're filing the NDA for the soft mist inhaler. It is in fact the ideal. It is the perfect product for that indication. But because the team running that clinical trial in PH-COPD is the same team that ran the TETON-1 and TETON-2 trials, their name for the PH-COPD trials is the SUMMIT Trial, and they have successfully summited more than once. Just for the audience's knowledge, PH-COPD is a form of COPD in which the PH symptoms are out of proportion to the COPD symptoms. While upwards of like 14 million Americans have COPD, and COPD and COPD emphysema are the largest causes of lung transplant, just a fraction of them have such a severe form that the PH symptoms are out of proportion to the COPD symptoms, and that's about 400,000 to 800,000 patients. Based on Dr. Aaron's work, based on our own earlier PERFECT work, which we have all of that data, based on the new development of our SMI, we feel we have all of the pieces in place to succeed. Nevertheless, we're going to go step by step. Quickly after the SMI device is submitted, we're going to start a phase II trial in PH-COPD and then very rapidly follow that in 2028 with the phase III trial. We think that the interest is going to be so strong that that trial should be able to wrap up by 2029, allowing us to file for approval in 2030 and then launch this product at the beginning of the 2030s. As Pat said, we've got intellectual property protection on the device and trade secrets going out to the 2040s. Great. Just remind us, I know you had to adapt the endpoints because of COVID, but what would the endpoint be for this new phase II trial? Would it be the original PERFECT study endpoint, or is it a new endpoint? What's the endpoint? Yeah, you'll have to wait until you see the filing and the protocol on clinicaltrials.gov. But the old endpoint were a combination of endpoints, including six-minute walks, spirometry, and some other stuff. There's a different clinical development team in charge of this one, and I don't want to prejudge any of their final decisions on the protocol, much less any interactions with the Cardio-Renal Division. There may be different changes in endpoint. The field of COPD is always moving. What I can tell you with a high degree of confidence is it would not be the kind of morbidity/mortality endpoint that you saw us successfully achieve in pulmonary hypertension. I don't believe that that's necessary. I would also point out that the controlling division of the FDA for this will be the Cardio-Renal Division and not the Pulmonary Division, and the Cardio-Renal Division has a high degree of familiarity with the indication with our treatment. Okay, great. Maybe just moving on to ralinepag. Again, another upcoming product launch. Just how do we think about inputs into the pricing decision here? Obviously, you have Orenitram already on the market, which is an oral prostacyclin, and so is that the best analog to think about here? How should we think about the early uptake curve for this drug? Sure. So taking the three points of your question, there is no doubt that ralinepag, or its commercial name, JENRALDI®, is a better drug than oral treprostinil. I say that despite the fact that Orenitram spells Martine Rothblatt, of my last name, backwards. So notwithstanding that, ralinepag is a better drug. I was just trying to do the backwards on JENRALDI®, and I couldn't figure it out. You can't figure it out. But the person that we started this company from, for my daughter, her name is Jenesis with a J. So you can kind of get the Jan and the ral from ralinepag. It beats paying somebody a quarter million dollars to come up with the drug name for you, right? That's what they charge, the Brand Institute or something like that. Some of them you can't even pronounce. So one, it is a better drug. Even though that would command a price premium, I don't really think there will be a price premium compared to Orenitram. I think the uptake is going to be quite strong because it will uniquely, among all the drugs in the PH space, be able to claim that its registration trial showed that about half the patients achieved a clinical improvement in their clinical status. Nobody else has ever shown that. So, it will be a pretty good call for the sales reps to say, if you want to tell your patient that they can improve instead of slow the decline, JENRALDI® is the only way to do that. Then if the physician says something like, "Well, my patient has at least been kind of stable on an ETRA or a PDE5," fortunately, those were most of the patients all were on that background therapy. So, we showed synergy with that. If the physician thinks they don't want to take their patient off of, say, something like Winrevair, we could show, well, we've already seen a lot of synergy between the prostacyclin class and Winrevair. So, I think not only is ralinepag the most efficacious drug for pulmonary hypertension, it's also, I believe, the most polypharmacy-friendly drug in pulmonary hypertension. Okay, great. Well, I think we're up against time, but again, really great to see you both. Thank you so much for taking time out of your day to spend with me, and best of luck. Thank you, Terrence. Thank you.