Welcome, everyone, to Jefferies Linden Healthcare Conference 2025. My name is Roger Song, one of the Senior Analysts who covers Mid-Cap Biotech in the U.S. It is my pleasure to have the fireside chat with our next company, United Therapeutics, James and Harry. Welcome, gentlemen. Thank you. Thank you. Thank you Thank you for having us and hosting United Therapeutics. Harry and I have had some really good meetings this morning, so we'll look forward to some more this afternoon. Excellent to hear. Excellent to hear. Awesome. We have a lot to cover, and United Therapeutics have very exciting news recently as well on top of the very solid business. Maybe we start with this current commercial business. James, can you give us some overview on all your kind of projection in terms of the growth trajectory, what we have been seeing, and then what we are about to see in the coming months and years for the current commercial? Yeah, thank you very much, Roger. It's a good question. Just coming off our Q3 report where we posted total overall revenue growth, but continue to have significant growth in total Tyvaso and Tyvaso DPI. These are going to be the growth drivers going forward with us. A lot of the uptake in Tyvaso in the quarter and going forward is going to continue to be around PH- ILD, so the uptake in that indication, as well as overall Tyvaso DPI. These will be the major growth drivers for us going forward. We continue to believe we're going to have this growth because of the product profile of Tyvaso and really our understanding and longevity in the pulmonary space. We continue to believe we're going to have growth there. One of the aspects when you think about growth on Tyvaso DPI, and we're going to talk about this, I think, a little bit more in some of your questions, but we feel really good about the product profile. For Tyvaso DPI, there's no dosing limitation with Tyvaso DPI for us going forward. From a prescriber perspective and a patient perspective, we've had a couple of good years of positive feedback and uptake. From a payer incentive perspective, we don't feel we're disadvantaged in terms of the payers or from the payers in the market. From a product profile perspective, we feel we have a superior product that has ease of use. For example, four times a day, one breath, and talking about or considering some of the new cartridge strengths that we have, we think this is an advantage for us going forward. Overall, Roger, on a going forward basis, we think we've delivered strong revenue growth, and we expect to have revenue growth going forward. Excellent. Yeah, we know recently you have a couple of new approvals in the PH-ILD space. You know, investors have been a little bit kind of cautious on the growth trajectory or the durability of the business, but so far seems looking pretty solid. Can you just give us any anecdotes? The number is good, right? We are always the one looking for some lead indicator. Can you give us some anecdotes in terms of the feedback from the field physician? How they think about a new patient or the existing patient? How they prioritize Tyvaso versus the other mechanism or the other drugs? Sure. Roger, I'm going to have Harry take this one. We're going to go back and forth today. Sounds good. Yeah, Roger. I'm assuming you're talking about Yutrepia here. You know, leading into their launch, they were trying to differentiate themselves, albeit using treprostinil. It's the same active ingredient, slightly different device, but they try to differentiate themselves on things like dosing and tolerability. You know, many of these things we refuted as recently as our first quarter earnings call, but James just talked about, you know, no max dose. Tyvaso is convenient. Tyvaso tolerability is well understood. As they've tried to do these things, we think real-world experience kind of catches up, and these things will kind of play out in the real world. Look, you know, we talked about on our third earnings call, our most recent earnings call, sure, when a new product comes to market, physicians are going to want to give it a try. It's something that you typically see in almost any new drug launch in any category. That's historically been the case for PAH as more therapies have come to market. Patients are going to, or doctors are going to want to give them a try. You know, despite this dynamic, what we've seen as we ramped up, you know, throughout the third quarter and into October, is that the referrals and start trends are kind of trending back towards us in our favor, basically to where they were pre-launch of Yutrepia. You know, while it's out there and while physicians have given it a try, I think in the real-world experience, the sort of factors that make us believe that we have the best positioned device play out. You're starting to see that come back in the underlying dynamics. Yeah. Thank you for that. It is interesting because it seems Yutrepia launch is, you know, trending towards a pretty positive way as well. Your business is also pretty durable. WINREVAIR, so the Merck drug, also, they are doing pretty okay. To me, it seems it is not a zero-sum game, and rather maybe with more education, with more attention, you will have more patients on those novel drugs and then for positive. Is that the sentiment you are also getting? It is, Roger. Thank you. What you see just as an analogy and going back to just the PAH space, when Martine started the company years ago, there were only a few therapies on the market, and there were roughly 3,000-5,000 patients. Now you look at the PAH market, and there is, you know, some estimates, 50,000 treated patients, but there is something like over 15 therapies in the market. What you have seen over time is you have seen new therapies come to market, more voice in the market, better diagnosis, and you have seen that addressable patient population expand. I think it is no different here. You are going to have another voice around Yutrepia in the market, which could expand the market, Merck's product WINREVAIR. When you have more voice in the market, better diagnosis, you can expand the available patient population. That could be the case that's going on right now with our products. You have seen us have a very good quarter in light of having a competitor come to market in the May timeframe. We expect that trend in terms of the growth of the addressable patient population to continue. That is part of our continued growth story going forward. Excellent. Okay. We also want to state the elephant in the room in terms of the ongoing litigation with Yutrepia. Obviously, you do not need to comment any legal kind of consequence here, but just internally or externally facing investors, what is your scenario analysis for this outcome out of this litigation? What will be potential impact, if at all, to your commercial? We just talk about the growth trajectory. I think, you know, it's been well forecasted, all these potential outcomes. At this point, it's in the judge's hands. We're not going to sit here and try and speculate or figure out what he's going to say. We're waiting on the decision just like everybody else. Whatever the outcome is, you know, it's in his hands for him to decide. Nonetheless, if it's an adverse ruling against us, we're going to continue to operate. They've been on the market for a full quarter, and we continue to grow 22%-23% growth for Tyvaso DPI in the third quarter of this year. Look, we've shown that we can continue to grow even with them being on the market. If that's the outcome of the ruling, we're still confident in our ability to grow. Okay. Great. So regardless of the outcome of the litigation, just assuming they have another inhaled treprostinil in the market, so you're confident about the Tyvaso continued growth trajectory? We are, Roger. I think in light of Judge Andrews' ruling, we feel very confident in our commercial portfolio. We feel very confident in some of the early clinical trials that are currently ongoing with TETON as well as Advanced Outcomes. From a commercial perspective, there's a lot of conviction in what we're doing and a lot of belief. That's what we're going to continue to do to keep our heads down and focused. Further, and we'll probably get into this a little bit later, there's a longer-term opportunity here with respect to some of the organ manufacturing opportunities. From an enterprise perspective, from a current commercial perspective, near-term pipeline and long-term pipeline, we feel very comfortable on the trajectory of the business. Absolutely. Yeah. We're definitely going to talk about IPF, TETON, and then also the transplant a little bit. Let's just wrap up the commercial business for now. I think in recent quarter, I think that's the first time I ever heard is you talk about the $4 billion run rate by 2027. Can you just elaborate on what's a component of the business? You have multiple products on the market, and also you are about to get approval potentially for IPF. Is that part of the projection, or that's mostly coming from the base business? Sure. It's a good question. One we've gotten this morning as well. What we talked about on the most recent earnings call is that we would have a quarterly revenue run rate by the end of 2027 of $1 billion. A couple of points related to it, the majority of that growth is going to come from the existing commercial business because that's what is approved and is currently being marketed by our sales and marketing teams. If you follow along the kind of estimated timelines, when you think about the TETON trials for idiopathic pulmonary fibrosis and the Advanced Outcomes trial for Ralinepag, approval for those would roughly be in the 2027 timeframe. Any revenue contribution that would come from those two products would be certainly additive, but they would be later towards that calendar year 2027. It would certainly be additive, but the bulk of the billion-dollar run rate is going to come from the expansion and growth of the current business, current commercial products on a going forward basis. That is kind of our target and our goal is to have a quarter of a billion-dollar run rate by the end of 2027. Got it. Just to set the stage for the investors as well, I think it is above at least the sales circumstances when I look at the projection for 2027. That probably, if you can achieve that or people start to believe or building the expectation, you can achieve that. This is upside for the current business. It is. That is what we are focused on, as Martine clearly outlined on the last earnings call. Awesome. All righty. Okay. We should talk about a very big upside driver from the IPF with recent very impressive TETON 2 data. I think with the more detailed data, people start to believe this is a real drug and then either as a monotherapy or the combination with the standard of care. How is your team thinking about this opportunity and then maybe just let us know what's the next step for the IPF? Yeah, sure. Just to quickly recap for those in the room, 96 ml benefit, placebo-adjusted difference on FVC. We hit statistical significance on most secondary endpoints in the study and well-known safety and tolerability profile of Tyvaso. We were really happy with the outcome from TETON 2, and we do recognize that it's a very large opportunity. What we are hearing from physicians is mirroring our own excitement for the opportunity and the availability of another therapy to add to the treatment armamentarium for IPF. Look, you know, I think your last question was the commercial opportunity. 100,000 patients in the U.S. And you know, just based on the existing therapies in the market, it's a multi-billion dollar opportunity that we're looking at here. Whether it shakes out based on the end label when we combine the two studies or when we have the two studies, you know, I think that will really determine what the overall market opportunity is. You are looking at a very sizable market no matter how you slice the pie. Got it. And then one of the key discussion points after the TETON 2 top line and the detailed data is how this will translate into TETON 1 data. You know, TETON 2 is ex-U.S. Canada, and then TETON 1 is the U.S.-Canada. So we did some deep analysis as well. So looking at the baseline, looking at the different kind of baseline treatment, and then the practice. So what is your conviction this will translate into TETON 1? And then honestly, when I see the TETON 2 data, the effects are so big, I believe you still have a chance to pull those together to enhance the filing package. So just tell us about the TETON 1 translation and then also the filing strategy with those two trials. Sure. I'll take part of it, and then Harry can add some too because there's a lot to the question. I think overall, the results of the TETON 2 clinical study in IPF were really successful, even from all the way down to a p-value perspective. We do have a lot of conviction as that translates over to TETON 1, which is your clinical trial for IPF in the United States and Canada. When you look at the baseline characteristics of the patient populations, they're very similar. We have a poster, I think a poster out on that. We wanted to share that with investors to see. Overall, there's a lot of conviction, Roger, that this would really translate from TETON 2 over to TETON 1. There's also the opportunity to pull the data as well overall. What am I missing in your question? Was there another? Yeah, I think that that's the translation. And then the fighting, you say you can pull the study. In what condition do you think you will pull the study to study, or is it necessary for the fighting package? Yeah. I'm not as smart unless you have any background on pulling the data. I think, you know, if it provides us an opportunity to maybe hit statistical significance on some of those secondaries that we did not hit on in the TETON 2 trial, that could potentially help the overall label, it is a possibility. And like you said, if perhaps the data are not as strong in TETON 1 versus TETON 2, you can pull it together and potentially get a statistically significant benefit. But again, based on everything that we can see, we are highly optimistic. Yeah. I was going to say, Roger, the conviction level that we have just on each individual trial is pretty high. We feel really good about kind of the overall results. TETON 1, which we will and we do still expect to unblind in the first half of 2026. I think you had a question on there about regulatory strategy filing, and I'm sorry I missed it earlier. One of the aspects that we've talked about is we are going to meet with the FDA by the end of calendar year 2025. One is we want to start to dialogue or really continue the dialogue with them regarding these two trials. We do need both trials at this point for approval of Tyvaso and use in IPF. That was the agreement that we did have with the FDA early on. That's why we're continuing to do these trials, one international, one domestic, because we also want to explore opportunities for Tyvaso ex-U.S. That's one of the reasons why we did the ex-U.S. trial. We are meeting with the FDA, or the regulatory teams are meeting with the FDA prior to the end of the year, and they're looking for any opportunity to continue to dialogue and to see if there are opportunities to accelerate any of the aspects around getting Tyvaso to market sooner for these patients. Because at the end of the day, the real motivating factor for us is there's a patient population that we believe we have a really beneficial therapy for, and we want to make sure we can take it to the market as quickly as possible. We also want to make sure we do it in a way that gives us the best opportunity for approval and the best label possible. That is why we are trying to be very methodical. We say at UT, we always have time to do it right. We are going to do it right, but we are going to try and accelerate it as well for the benefit of the patients. Absolutely. Okay. Great. I think IPF, as Harry mentioned, is 100,000 patients. No matter how you look at the pipeline, look at the market size, and it can be multi-billion at the least. We know we have two standard of care. It is not best drug, and they are still getting towards like a $4 billion market. We agree with all the above. It is a very large opportunity for us. I think what will be interesting is, and I talked about this earlier, what the ultimate label would be. If you think about the clinical trial, there were certain aspects, and Dr. Nathan talked about this at the unblinding in terms of quality of life attributes. No study has had a benefit that we have seen in terms of patient quality of life. There are many attributes in the study in terms of how we want to take advantage of that, whether it is through the FDA approval process and from a marketing perspective. Excellent. All right. I know we have a lot to cover. We already talked about the base business. We talked about IPF as a major next kind of leg for the growth. We still have a couple more, right? First, maybe on the PPF side. I think that's still the Tyvaso TETON PPF. With this IPF data, what's the level of conviction you now in terms of likelihood of success for PPF translate from IPF, if any? Yeah, thanks, Roger. Look, we're equally as excited about PPF. When you think about the disease progression and the underlying fibrosis relative to IPF, it's more or less the same. Based on what we've seen thus far in the TETON trials, we're confident and optimistic that we can see a similar outcome in PPF. Okay. I think just to add on to Harry's, I think we've talked about this. I think the addressable patient or the patient opportunity is about 60,000 patients. Another sizable opportunity for UT if that is successful as well. Yeah. Okay. Great. You have an oral once- daily Ralinepag. This is also data going to read out next year. What is the winning profile you are looking at for this drug? I believe last quarter you talked about the oral combination that piqued a lot of interest there. What is a strategy for fits into your PAH performance? Just a quick summary, we're doing a timed clinical worsening study with Ralinepag, which should read out in the first half of 2026, on a similar timeline to TETON 1. A win for us, this is going to be a once-a-day oral prostacyclin that we think will have more potency and higher efficacy than selexipag. This would be a once-a-day that we could move up into the treatment paradigm. We've talked about combination strategies historically as well. We think this would be something that would be really beneficial for patients from an upfront diagnosis perspective. To reference your point, what we did or Martine did talk about on the last earnings call is if this is successful, this could be a pretty significant opportunity and interesting opportunity to partner a once-a-day oral with other therapies that are currently on the market. You have a once-a-day form of therapy, which is great from a compliance perspective. We've had some history with other therapies, one called Adcirca, where it was a once-a-day, and you could see the benefit from a compliance standpoint to patients. We are very high on this clinical trial. On the last earnings call, Martine outlined why she was very enthusiastic about it. Again, we're excited about kind of unblinding this in the first half of 2026. Excellent. Great. Another, you are starting to develop a once-daily inhaled treprostinil or the prostacyclin. We know we have another company also in this conference, and they have this once-daily inhaled version of the treprostinil. How do you think about the development timeline look like, and what is your potential profile for the future of the market? Yeah, thanks, Roger. We are developing a QD NCE for PAH and PH-ILD. We'll share more with you guys probably next year once we get through Advanced Outcomes in TETON 1. The product development teams are really focused on those right now. Once we get through those, we're happy to share more. Yeah, sure. Okay. We're going to talk about transplant, right? The organ transplant, that's a huge upside. I don't think any buy-side or sell-side model is including that, in terms of the value and the credit. Also, it's a massive man need, and you are in the clinic, right? You just did the first transplant. Tell us a little bit about this rationale, the strategy, and when we're going to start to see the data for potential approval. You bet. Thank you for asking. It's a strategy that has been in the works for years, and we're pretty excited about it. In our PBC charter, one of the aspects of our public benefit corporation is to invest in technologies that expand the number of transplantable organs. What we recently have done under what we're calling xenotransplantation is we did a first transplant in the EXPAND clinical trial of a kidney into a human. From the standpoint of going forward, you're right, Roger. The opportunity and really the need in this space is significant because there's a huge and incredible shortage of transplantable organs. We are first focusing on the kidney, but we're also planning to do other aspects or other products in the lung and the heart as well. We recently had another IND approved for the Thymo Kidney. It is an aspect of the organization that we're pretty positive on. There's a lot of research and development going on, and we're pretty excited about this most recent transplant. The one thing that we've talked about this morning is the communication protocol around this clinical trial will be somewhat different than some of the expanded use cases that you may have read about because those were patients that were part of the hospital's network system, and we supplied the organ. These are approved FDA clinical trials. The cadence may be a little bit less, but rest assured, the first one has happened as we talked about, and we're progressing on other products as well in this space. Excellent. Great. Maybe just lastly, I think UT has been a very successful standalone biotech company. What is your overall partnering strategy as a biotech company? Also maybe touch on a little bit on your financial position. From a strategy perspective, and we've had this conversation this morning, we're very comfortable both on the commercial side of where we are on our near-term clinical pipeline, which we've talked about, but also this longer-term view of the manufactured organ pipeline. From a corporate perspective, from a strategy perspective, I think we've clearly communicated where we're going, and I think everything is lining up and progressing extremely well internally on a going-forward basis. Okay. Awesome. I think we have this time, and then I really appreciate spending this with us this morning. Thank you. Thank you, Roger. Thanks, Roger. Thank you very much. Thank you, everyone.