Please also note today's event is being recorded. At this time, I'd like to turn the floor over to Mr. Harrison Silvers, Investor Relations Manager at United Therapeutics. Thank you, Jamie. Good day, everyone. It is my pleasure to welcome you to the United Therapeutics Corporation Phase III ADVANCE OUTCOMES Clinical Trial Results Conference Call. Remarks today will include forward-looking statements representing our expectations or beliefs regarding future events. These statements involve risks and uncertainties that may cause actual results to differ materially. Our latest SEC filings, including forms 10-K and 10-Q, contain additional information on these risks and uncertainties. We assume no obligation to update forward-looking statements. Today's remarks may discuss the progress and results of clinical trials or other developments with respect to our products. These remarks are intended solely to educate investors and are not intended to serve as the basis for medical decision-making or to suggest that any products are safe and effective for any unapproved or investigational uses. Full prescribing information for products is available on our website. Accompanying me on today's call are Dr. Martine Rothblatt, Chairperson and Chief Executive Officer, Michael Benkowitz, President and Chief Operating Officer, Dr. Leigh Peterson, Executive Vice President of Product Development and Xenotransplantation, Dr. Derek Solum, our Senior Director of Product Development and lead for the Global Advanced Outcomes Program, and Dr. Daniel Lachant, Associate Professor of Medicine at University of Rochester Medicine and one of the principal investigators on the ADVANCE OUTCOMES study. I will turn the webcast over to Martine to begin our overview. Martine. Thank you, Harry. Good morning, everyone. There are days for which you work your entire life. This is that day for me and dozens of my teammates at United Therapeutics. Today is the day we announce that we proved our unique pill, ralinepag, a new chemical entity, is more than three times likely to avoid disease progression events from pulmonary hypertension as compared to taking the standard of care background double therapy of an ETRA and a PDE5 inhibitor. When, like me, you have a daughter with pulmonary hypertension, slashing the likelihood of disease progression is everything. This is a remarkable result, not matched in any trial of a prostacyclin or a pill that I'm aware of. This is why I call ralinepag a super prostacyclin. It is just once a day orally. It has greater potency, meaning receptor binding, than any other prostacyclins. It is uniquely durable in its clinical trial results that argue for frontline treatment promptly upon patient diagnosis. It has best-in-class pharmacokinetics with the longest half-life and most stable plasma concentrations. This is what powers its once daily dosing. No other prostacyclin or pill of any kind has ever met its clinical worsening endpoint in PAH with a hazard ratio nearly as good as the 0.5 that we unblinded today. 0.45. Wow. Our clinical trial met its primary endpoint with a P value of less than 0.0001. In addition, in our secondary endpoints, we showed a statistically significant clinical improvement compared to background therapy and as soon as 328. Indeed, our treated group was 47% more likely to improve. Again, just speaking as a parent, this is huge. Because ralinepag is so favorably differentiated from other prostacyclin-based pills, based on these pivotal trial results, I believe if approved by the FDA, doctors will prescribe and payers will reimburse ralinepag not only in lieu of such pills, but as frontline therapy. The trial we unblinded today shows that ralinepag works in every type of subgroup that we analyzed. This gives me great confidence that it will become prescribed for tens of thousands of patients, more patients than all of our current drugs combined. The data we are sharing today supports all patients on single or double background therapy, at least 30,000 in the U.S. alone being prescribed ralinepag as well. This is transformative for PAH, transformative for the lives of all the patients, their families, and their healthcare teams, and transformative for all of us at United Therapeutics. Today would be the best day in the life of any biotech company. Yet, I want to remind everyone that just last quarter, we unblinded our TETON trial, showing that our Tyvaso medicine had the best clinical trial results for pulmonary fibrosis of any drug ever approved by the FDA. I don't think a biotech company could be in a better position than are we. Our best-in-class news is flying in formation, marking the skies with solid statistical proof that in our diseases, no one has better science, technology, and execution capability. This is the day we have been working for since we began working at United Therapeutics. This is the goal we've been striving for over the past decade, proving that we have a unique proprietary pill that is well-tolerated and that has proven beyond a shadow of a doubt that it is effective in multiple ways, even on top of dual background therapy. This is a wow moment for the field. I'm now going to turn the call over to the scientist who proved this wow. Our company's lead ultra-marathoner and 100 miler outcomes clinical trial leader, Dr. Derek Solum. Derek Thanks, Martine. It's a real privilege to be here today and to get to share these exciting results. As Martine noted, this is a project we have been working on for many, many years. it's great to see the fruits of our labor and to be able to share these exciting results with you. I'm going to spend just a little bit of time sort of level setting so everybody kind of remembers what the study is about because it has been a few minutes. as you can see on the slide, the primary endpoint for this study is a time to first adjudicated clinical worsening event. The study was straightforward in that it was randomized 1-to-1. One participant received active ralinepag for every participant that received placebo. We powered the study to find 180 adjudicated events before we could, before we could close it. The study was powered with at 80% to determine a 0.65 hazard ratio in the study. We also wanted to look at a number of important secondary endpoints that speak to the disease state, and to the study results. That those secondary endpoints are listed on the slide. Predominantly, it's a change from baseline to week 28 in the usual suspects, the NT-proBNP, six-minute walk distance, functional class, et cetera. We also added a very important endpoint, the clinical improvement endpoint to the study, because we feel that not only do we want to demonstrate that you can delay participants' disease from getting worse, but we wanted to show that it got better. We added this endpoint into the study. There's a number of others that are listed on the slide, and I won't go into a lot of details here, but suffice it to say we were looking at a lot of ways to determine whether or not ralinepag really demonstrated a, you know, a clinically meaningful change in people who were in the study. If we can go to the next slide. I want to kind of get a detail around what the clinical worsening definition is because it's a little complicated. It's a composite definition, and you can see in the bullets on the slide that that composite composed of all-cause mortality, non-elective hospital admission, and that needed to be at least 24 hours, and it needed to be due to PAH. You could have also met the definition by initiating parenteral or inhaled prostacyclin therapy. We have a disease definition, disease progression definition, which is a composite in and of itself, including a six-minute walk distance drop of 15%, worsening of functional class, or initiation of additional escalation of PAH therapy. We also added an unsatisfactory long-term clinical response criteria because for a study that goes on this long, we wanted to make sure that anybody who maintained functional class III or IV had any drop in their six-minute walk distance after 28 weeks of treatment would meet that definition because we really, like I said before, wanted to not just show that we could delay people from getting worse but really getting better. Anybody who was not improving, we wanted to be able to allow them to move to the open label extension study. I didn't emphasize that, but anybody who met the definition could move to the open label extension to receive active ralinepag. We also moved everybody else at study closer to the open label extension study as well. This is the kind of key point to the study design. Harry, if you go to the next slide, please. The baseline demographics are pretty important in this study because what it really speaks to is the fact that this is a contemporary real-world study. You can see that the age at study entry is predominantly in the 1950s. It predominantly affected females, and those are not huge surprises other than we're seeing participants a little bit older. You can see the time since diagnosis that overall was about 4.5 years. The specific ethnicities and races is not a real surprise, but it does speak to who we are seeing in the clinic. You can kind of see the breakdown there. More importantly, if we go to the next slide, continuing the baseline demographics is I want you to kind of key in on the background therapy. You can see that, importantly, 80% of the people in the ADVANCE OUTCOMES study were on dual background therapy, predominantly an ERA and a PDE5. 20% of those were on monotherapy. Again, ever since the publication and of the AMBITION results, the community has adapted their change to start people on dual combination therapy. That is most of the people who were enrolled in the study were on two backgrounds therapy. They're a heavily pre-treated population. If you look at the baseline six-minute walk distance, you can see that on average, participants were walking about 440 meters. They're meeting that low risk criteria threshold. This is an early disease state population. We did stratify the study and eligibility, and you can see that one of those stratification factors was above and below 400 meters. Again, you can see that predominantly people were walking over 400 meters. Lastly, you can see if we look at through functional class that the vast majority of participants were in the functional class II category with a few functional class III, about a third of those. We did allow people who were functional class IV, but we only had one participant who was enrolled with that criteria. Again, overall, the take-home message is that this is contemporary, this is real world, and it is the type of participants that we're seeing in the community. I also don't have a slide, but I do want to emphasize that we did want this to be real world, our eligibility criteria are aligned with current ERS/ESC guidelines, and we've taken into consideration the recommendations from the World Symposium. Our hemodynamic eligibility criteria meet those. It's really important to see that this study does really enroll the people who we're seeing in the community now. Now, Harry, if you don't mind going to the next slide. This is my favorite slide that has been sort of burned into my retinas recently. You can see this is the Kaplan-Meier graph that shows the separation. The blue line is ralinepag, red line is placebo. You can see that separation happens very early. Then the separation between the treatment and the placebo groups is robust, it continues, and it is very durable. This Kaplan-Meier graph goes to four years speaking to the durability of the treatment effect. Importantly, you can see, this was shown on the intro slide, that the significance, we are so incredibly confident because this is a highly statistically significant difference with a hazard ratio of 0.45 demonstrating a 55% reduction in the risk of achieving a clinical worsening event. We couldn't be happier with these results, it's taken us a long time to get there, but the durability in treatment effect in this heavily pre-treated population really speaks volumes to how well this molecule works. Kind of carrying on, Harry, to the next slide, you can see the breakdown of the primary endpoint. I gave you the definition a little bit earlier. What you can see here is that the driver of the clinical worsening definition was disease progression. You can see there is a three-fold decrease in the number of people who had disease progression in the active treatment group. We also saw benefits of the initiation of inhaled or infused therapies and that unsatisfactory long-term clinical responders. We've done sensitivity analyses where we've removed the unsatisfactory responders from this population, and we find that the numbers really don't change. It's a 0.49 hazard ratio, and significance is still just as good. We weren't surprised to see that there were not many hospitalizations or death because I want to emphasize that this is a intermediate low risk population, heavily pre-treated. The fact that we have such low mortality across the study is really no surprise, and in fact, a good thing really. Harry, if you go to the next one, I want to just continue to drill down on that, the impressive results in the disease progression. Here you can see the Kaplan-Meier graph, and again, very, very early in the treatment, within a few weeks, you see separation between the treatment group and the placebo group, and that separation does not change. In fact, it just continues to grow, and we're really just pleased with this four-year period that we're demonstrating here. Again, a hazard ratio showing a 75% reduction in risk that is highly statistically significant. Very, very great results that we're very happy to see. Moving forward again, Harry, I want to just emphasize, the importance of what the study results mean, and that's using this forest plot with a lot of subgroup analyses. You can see that in the middle is the break between where we favor ralinepag on the left and placebo on the right. I just can't emphasize enough that it doesn't matter what treatment subgroup you are in. Ralinepag still shows a highly significant difference. It doesn't matter if you're walking 400 meters or more. It doesn't matter if you are in the CTD etiology or if you have the other etiologies. Excuse me. It doesn't matter if you're on 1 background therapy or 2, if you're young or old, or if you're male or female. Every single subgroup analysis strongly favors treatment with ralinepag, and we're just so happy to see this. Again, moving forward to more subgroup analyses, we can see that again, it doesn't matter if you're functional class two, three, or four, or if you're on an ERA or PDE5 or both for that matter. We don't have a dose limit in this study, but we find that also doesn't matter, that you could be on a less than 600 microgram dose, or you could be over, and it still shows very significant. It doesn't matter if you're in Brazil or France or in Singapore. All of the results geographically demonstrate that there's a nice significant benefit to being treated with ralinepag. One more group here, if you don't mind, Harry, is to look at some of the baseline hemodynamics, and we can see that, regardless of where your hemodynamics lie, if your mean pressures or your PVR, we still see great benefits. It also doesn't matter what your NT-proBNP is or how long you've had the disease. It just emphasized that we should be adding this early in order to delay the disease from progressing. The last little group you see on this slide is the baseline risk category. So this is the low-risk category. So, if you Which breaks down into the walk, the functional class, and the NT-proBNP, and you could either have none of those low-risk criteria or all three. We still show benefits, just across the board. So impressive. Moving forward just a little bit. I do want to just touch on the side effect component because we have a very robust pharmacovigilance group who's been working on this project from the beginning. Because this is a new chemical entity for us, we wanted to make sure that we didn't miss anything. You can see that there is no surprises here. The adverse events that we see are the usual suspects for prostacyclins, headache, diarrhea, nausea, mild chills, and jaw pain. Again, not a surprise in the percentages, more in the ralinepag-treated group, but also not the numbers, not, you know, too overwhelming. For a study that went on for seven years, it's not a surprise to see these sort of numbers. No surprises from a safety standpoint, which is great as a clinical trialist. That's always one of the first things we want to make sure, and just such outstanding efficacy results. With that in mind, I just want to Harry, if you go back to the summary slide really quick, just to really emphasize on how significant the results are here, that we benefited the delay from disease progression. We also have a lot of key secondary endpoints that we'll be disseminating in the coming weeks. Also the safety profile is as we expect. With that in mind, I actually want to turn it over to a colleague and friend, Dr. Daniel Lachant, who is an Associate Professor of Medicine at the University of Rochester. Dan has been on the study, from the very beginning. He's the highest enroller in the United States, and he has as much experience, with the, with the molecule and with being in the study as anybody. With that in mind, Dan. Perfect. Thank you, Derek. As a physician who treats pulmonary arterial hypertension, I share Martine's enthusiasm, and I'm just so very excited for these results, and to be here today to talk about ralinepag. First off, I just want to thank all the patients who participated in this study, all the sites in United Therapeutics for conducting and completing this pivotal study through the COVID-19 pandemic, a very challenging time, and they came out on top with home run results. Someone who uses a significant amount of oral and parenteral prostacyclin therapy in pulmonary hypertension, these results once again are just amazing. Based on my experience in this study, the results track with what I observe clinically. To have a once-a-day titratable prostacyclin receptor agonist with comparable or improved tolerability relative to our other oral therapies currently approved and show such an impressive reduction in clinical worsening. What's been said multiple times, a contemporarily treated cohort patients, nearly 100% on background therapy, 80% on dual combination therapy, primarily functional class II, high baseline six-minute walk distance is just that's what blows me away and gets me excited about this data. No other oral prostacyclin has shown such impressive results like this. Selexipag, which showed a reduction in clinical worsening, and they had a much higher risk cohort of patients, so it's easier to show that kind of a benefit. Only a third were on dual combination therapy, so it's really hard to extrapolate those results forward. Subsequent trials of selexipag in the setting of dual background therapy didn't show any benefit over placebo. Oral treprostinil showed a reduction in clinical worsening, but that was more in monotherapy patients and after recent diagnosis. In this well-treated functional cohort with an average duration, once again, it's been said, of four years, ralinepag was able to reduce the risk of clinical worsening with curves diverging around week eight to 16 and remaining separated throughout the remainder of the study. Importantly, it also showed improvement in 6-minute walk distance during a clinical worsening study, something that's very difficult to do, something that wasn't seen with the other oral prostacyclins. Even in a 6-month study, having such a high baseline to begin with makes it even more impressive that ralinepag was able to show that. As Derek just went over, all the subgroup analyses are internally consistent with the primary findings, which is great to see that everybody benefits from the drug. Like Derek said, it doesn't matter the type of PAH, it doesn't matter where you start, doesn't matter what your PVR is. Everybody found benefit from ralinepag. And once again, the patients are representative of non-parentally treated patients in a traditional pulmonary hypertension clinic. If you're on background therapy, you're typically functional class!!, and these etiologies of PH is what we see in our clinic. It just makes the results more translatable and easier to explain to patients, which is great. With the frequent study visits and proactive evaluation to pick up changes in the patients in the study, I'm not surprised about the clinical worsening outcomes just being clinical worsening disease progression and unsatisfactory response. That hospitalization and mortality aren't hidden. That's just because we're so attuned and good at picking up changes sooner that we don't let patients progress to that part. I'm not surprised that there was no changes with those or no difference between the two. The side effects reported are also what would be expected based on the mechanism of action and similar to what we see with other prostacyclin therapies. As Derek said, we enrolled 14 patients at our site. We were able to manage side effects in all of them. No patient dropped out because of untreated side effects or inability to tolerate ralinepag, which just speaks volumes about the once daily pharmacokinetics and tolerability. Even early on in the COVID-19 pandemic, patients who had started the study were willing to drive 10-hour round trips to continue in. We had patients flying back from different parts of the country to complete study visits because they didn't want to give up this drug. They felt that the benefit they were experiencing was just worth it for them. One thing is ralinepag may be showing us that prostacyclin side effects, although the pharmacokinetics definitely are better, they may be more manageable if patients actually feel a clinical benefit to go along with it. Instead of just preventing clinical worsening, when patients feel improvement in their exercise capacity, side effects become more mild and easier to tolerate. There's been over 1,000 years of patient observation on ralinepag so far, and there have been no new unexpected side effects attributed to ralinepag. Ralinepag also has the benefit of not needing frequent lab draws to monitor blood counts or anything else. The titration also makes it easier on patients and providers to make adjustments. Based on the current data, ralinepag has the potential to be used in many different clinical scenarios following approval. Early on after initiation of combination therapy, even frontline therapy in some patients and stable patients on background therapy to prevent clinical worsening or help improve functional capacity further. The data supports its use in all those different areas. Future studies still need to help better understand transition options for select patients who are well treated on parenteral Remodulin. Potential strategies for using parenteral Remodulin to achieve higher doses of ralinepag quickly, similar to strategies evaluated in the EXPEDITE study. Even more exciting is a replacement for other oral prostacyclin therapies, that are more burdensome in administration and have significantly more side effects which greatly impact quality of life. This is just an exciting time for patients with pulmonary arterial hypertension as the number of therapeutic options continue to expand. Ralinepag does have the potential to become a preferred oral prostacyclin therapy early on. It's durable and has clinically meaningful reduction in something we all care about. The flexible titration makes it so that, you can find a dose for every patient that provides benefit. Importantly, its side effect profile is just so much more favorable compared to what's currently available, and this allows it to potentially become a broader access to the prostacyclin pathway in all patients with PAH. Now I'll turn the call back over to Martine to close. Thank you so much, Dr. Lachant. That was like the best 360-degree coverage of everything from the trial and the, and the treatment realities that exist today in the next few years. Again, as a, as a parent of a patient and one who knows many, you're a blessing to the field. Thank you so much, Dr. Lachant. Operator, you can now open up the call to any questions. At this time, we'll begin that question and answer session. To ask a question, you may press star and then one using a touch-tone telephone. To withdraw your questions, you may press star and two. If you are using a speakerphone, we do ask that you please pick up the handset prior to pressing the keys to ensure the best sound quality. Once again, that is s tar and then one to join the question queue. Our first question today comes from Andreas Argyrides from Oppenheimer. Please go ahead with your question. Good morning and congrats on these impressive results. Thanks for taking our question. How, how are you thinking about the opportunity for patients to switch from to a once daily from a twice daily given the strength of these these results? And how big do you think ralinepag can really be? Again, congrats on these results. Thank you for the question, Andreas. Derek has really the most experience with all of the dynamics of the different oral medications for treating pulmonary hypertension. Derek, could you answer that question? Sure, Martine. Thanks, Andreas, for the call. I think, any time you can reduce the pill burden for this patient population, I think you have a great opportunity. you know, like I said, the population is heavily treated. They already take a lot of medications, I think just from a compliance, that if you can reduce their pill burden, improve the patient compliance, ultimately that's going to really speak to the durability and effect. I think that in itself is a big factor outside of the fact of the pharmacokinetics and the treatment effect here. I think that was the primary point of the question, yeah. Thank you, Derek. Thanks, Derek. Andreas, another thing that I would add, again, being very close to the patients, when there is a new pill that comes out that demonstrates these sort of results in reduction of disease progression and somebody is on another pill that has not demonstrated these results, as Dr. Lachant explained, it's I think very highly incumbent upon the healthcare team to go ahead and make the switch that you're referring to. Certainly if you put yourself in the shoes of a patient, you would ask for ralinepag. Next question. Our next question comes from Roanna Ruiz from Leerink Partners. Please go ahead with your question. Hey, morning, everyone. I was curious, how should we think about prescriber uptake of ralinepag in PAH, given how some other newer agents like sotatercept are layering into the treatment paradigm and possibly moving into earlier line use as well? Thanks, Roanna. Since we have a great prescriber on the call, I'd like to ask Dr. Lachant to kindly answer that question. Yeah, that's a great question. Based on my experience with the study, based on the data that was just presented today, and based on the ease of use, the way I see this playing out for a new diagnosis patient is they're started on initial upfront combination, and once they get situated on a steady dose, I plan on layering ralinepag next. I think it's a well-tolerated once-a-day pill. Thanks so much, Dr. Lachant. Operator, next question. Our next question comes from Louise Chen from Cantor Fitzgerald. Please go ahead with your question. Hi, good morning, and thank you for the question and congrats again on these results. Can you give us any details at this point around adverse event profile just in terms of severity for some of those events? I think I heard that there were no discontinuations due to AEs. Can you just confirm if that's the case? Martine, I just wanted to ask you kind of more broadly as you think about the PAH market, where ralinepag really fits into your overall commercial strategy, especially in light of last week's soft mist inhaler disclosure. Thank you, guys. Sure. For all of the first questions you asked about AE, Derek would be, I think, the best person to talk about that. Derek? Yeah, absolutely. Louise Chen, no, it's not true that nobody discontinued due to AEs. We did have discontinuations overall in the study. It was a lot, 11%, less than 10% in the active group, so much better than the other pivotal trials in the space. The AE profile was very consistent with other prostacyclins, I showed that kind of at the end with headache, nausea and myalgias are kind of the lead AEs. Ultimately I think that the profile matches the long half-life and allows us to kind of titrate into a treatment effect that avoids the severe AEs. We've collected a lot of data around that, we'll be disseminating that in the future in granularity around the AEs. Like I said, there was no safety signals that were unsurprising here. Thanks, Derek. Louise Chen, with regard to the amazing product we announced last week of TreSMI, the way to think about pulmonary hypertension, at least the way we think about it is, you know, inhaled is a very different kind of situation from the rest of PH. Inhaled is primary focused on the ILD population, where there's been a legacy of data contraindicating systemic treatments. We see that the TreSMI product is perfect for the ILD population, where it can reduce by up to 90% the main side effect causing people using DPIs to discontinue or even not to really start. We think that the SMIs can cover that entire space. There are, there is a portion of the non-ILD population that does use inhaled therapy. Now that it's available to have just a once-a-day pill, it would be kind of like... I mean, there will always be some people using every type of therapy. I think from the patient's perspective, the prescriber's perspective, it'll be much better just to take one, you know, a pill once a day than to go ahead and deal with the multiple times a day inhalation. I should also mention at this point, Louise, that in our skunkworks division where we develop new products like the SMI that we announced, we are also working on a once-a-day combination pill that would combine the ERA PDE5 as well as ralinepag. Just in a single dosage, the patient can get all of that. That will be, you know, more formally announced as we move a little bit deeper into the year. Next question. Our next question comes from Roger Song from Jefferies. Please go ahead with your question. Great. Congrats for the data as well, thank you for taking our question. My question may be related to the access, reimbursement. How should we think about this data is mostly in the intermediate risk, seems more suitable for earlier stage of disease? How should we think about this will be used as a first line versus the selexipag maybe go to a generic in the near term? Also related to the hospitalization and deaths impact, understanding this is, you know, a little bit lower risk population and how this profile will impact the payer decision. Thank you. Wow. There's a lot of questions there. There's so many people on the line. We're only gonna really take, you know, a subset of all of them. I'd like to ask Dr. Lachant to respond as best you could to that array of questions basically relating to how you expect to use ralinepag in your practice. Yes. ralinepag and it's kind of like how we think of statin therapy, is when you're preventing clinical worsening, you're preventing somebody from experiencing something they don't know would have happened. Because of that, it's better to start it earlier when they're well. Once again, prostacyclin pathway is a pillar in pulmonary arterial hypertension. Having an easy, well-tolerated medication that can target that pathway, even if you start out at lower doses and titrate up over six months, I feel like it'll prevent or provide great benefit to patients. For me, the way I'm gonna start looking at this once it gets FDA approval is offer it to patients 1 month after diagnosis, saying, "This is something that's gonna pay dividends in the future." I don't care about one, three years. I'm caring about 10, 15, 20 years down the road. If the best way to maximize this is to start early, that's what I'm gonna offer to patients. Thank you, Dr. Lachant. I'll just add, like, one more comment with regard to your question, Roger, about selexipag going generic. I think it's completely irrelevant. This data is much better than the data that came out of the GRIPHON study. We saw exactly this same situation when sildenafil went generic. We were selling branded Cialis, you know, tadalafil, and we called it Adcirca. And when it was, again, much simpler for the patients to take once a day instead of multiple times a day, amazing data. And the vast majority of the prescriptions went to Adcirca. Sildenafil going generic was an irrelevant data point. I think the same situation will be the case with selexipag. It will simply become irrelevant in terms of the prescribing patterns of physicians in this field. Operator, next question. Our next question comes from Lisa Walter from RBC. Please go ahead with your question. Hello, good morning. Thanks for taking our question, and congrats on the results today. Just curious, maybe a question for Dr. Lachant, if he's still on the line. Wondering if you can expand how you would use ralinepag in your patients in your practice today if the drug was ultimately approved. Would you start this in new patients? Would you switch over existing patients from other treatments? Any color here would be helpful. Thanks. Thanks. Dr. Lachant? Yes. Great question. Dr. Lachant? Yep. I would certainly start it in all my new patients, one month after just getting the other therapies on board just to minimize side effects. As you're starting a drug, you don't wanna blast necessarily right away and just get things cooled down. To your question about transitioning, as Martine said, and I agree 100%, just like we figured out how to transition patients from selexipag to Orenitram, I would start doing that early. In patients who are well compensated, lower doses of oral prostacyclins, I would offer ralinepag as a potential option for them. Then as further data comes out and we figure out how to transition from stable Remodulin and things like that, my personal experience, we had one person who was on ralinepag who had to go on Remodulin because of clinical worsening, the doses that person achieved was astronomically high without any Remodulin side effects. To be honest, I don't think the person improved after we put them on Remodulin. I'm not sure we really did them a favor. We followed what we thought was the best decision, but I don't know if it was the best for the patient. ralinepag just has a very potent receptor profile, and because of that, you get benefit that almost all patients, like Martine said, not every patient, but a lot of patients will be able to benefit from. Thank you so much, Dr. Lachant. Next question, please. Our next question comes from Jason Gerberry from Bank of America. Please go ahead with your question. Hey, guys. Thanks for taking my questions, and congrats on the data. Wondering, I think you guys in a prior call mentioned running studies with prostacyclins in combination with Winrevair in early patients. Given kind of how you framed SMI versus ralinepag, is it fair to think that, you know, any future combination studies with Winrevair would be with ralinepag and not SMI? Your comment about only a small portion of, I think inhaled sales coming from non-ILD settings. I think in the past there was something like a 50/50 kind of revenue split or understanding of PAH versus PH ILD. Just wondering how 2025, if you can kind of give us an update on how that revenue split, looks. Thanks. Because we're gonna focus this call on ralinepag, I'm gonna skip over the revenue split question, which was kind of a little bit convoluted anyway. Just going right to the combination with Winrevair here. Yes. In fact, our discussions with its sponsor have focused on ralinepag as being the most logical agent to combine it with. Next question. Our next question comes from Terence Flynn from Morgan Stanley. Please go ahead with your question. Great. Thanks so much. Congrats on the data. One for Dr. Lachant. I was just wondering if you look at, you know, your potential ralinepag use on the forward, if you think you'll use it in a similar number of patients or more patients than your current number of patients on Uptravi and Orenitram combined. Just trying to understand if you see this expanding the oral market or ultimately over time, if you're gonna have a similar number of patients on oral prostacyclins. Thank you. Oh, I think this is greatly going to expand-. Dr. Lachant. Yep, I'm sorry. I think this is greatly going to expand the oral prostacyclin market. There are many patients who, we kind of talk about saying, "Oh, this person would be great for an oral prostacyclin." Because of their milder disease status, we just say the quality of life impact sometimes isn't worth it. In some fraction, I can't give it to you maybe 15%, 20% of patients where we're like an oral prostacyclin would be good, but we just can't justify it. This is exactly where ralinepag will fill that market and expand who can actually get treatment through the prostacyclin pathway. Perfect. Thank you so much, Dr. Lachant. All righty. Well, I think that wraps up all the questions in the queue here. By way of summary, I want to thank Derek and his team, Dr. Lachant, and all of the other investigators. This is some really extraordinary science that we've been able to share with everybody today. It's especially amazing for me because so often in business, timing is everything. Here, as was elucidated in the call, selexipag did their trial at a time when there was one background therapy, predominantly a PDE5 inhibitor, and the era of dual background therapies was kind of just over the horizon. They were not really able to enroll very much of the trial in the dual background therapies. As Dr. Lachant explained, as the years rolled on, it was later shown that it really was not that effective in the dual background therapy arena. Whereas today, a dual background therapy is all but universal, and the timing of this ADVANCE OUTCOMES therapy was just like a great surfer catching a great wave. You know, we caught the dual background therapy wave perfectly with the timing of the enrollment of ralinepag. As a result, we have a best-in-class result, extraordinary efficacy, you know, hazard ratio not seen in any other drugs. All of this on top of the real reality that is in pulmonary hypertension today, and very likely to be the reality of background therapy for the next decade to come. I just wanna thank everybody for all of their contribution to this study. Of course, I'm in huge gratitude to all of the patients from throughout the world. Derek has traveled an insane number of miles around the world enrolling this study. Just to give you a couple of anecdotes, there is a patient who has been on ralinepag now for 12 years, doing very well, and that patient is in the Ukraine. The patient was a phase II patient who rolled over onto open label therapy. Derek and his team have been adamant about making sure that every patient on open label and, of course, in the trial itself, gets their therapy no matter what. Through the war in Ukraine, this patient has been delivered his, their medicine and 12 years still doing very well. Similar situation for patients in Israel through the course there. As Derek mentioned, through COVID. It's just an amazing execution of a trial, and I cannot give higher kudos to the physicians, the patients, all of the clinical trial team. We had well over 100 United Therapeutics employees dedicating themselves to this for years and years and years. Thank you, everybody, for listening. Operator, you can now wrap up the call. Thank you for participating in today's webcast. A rebroadcast of this webcast will be available for replay for one year by visiting the Events and Presentation section of the United Therapeutics Investor Relations website at ir.unither.com. Again, that is ir.u-n-i-t-h-e-r.com. Thank you for joining. You may now disconnect your line.