United Therapeutics Corporation

Good morning and welcome to the United Therapeutics Corporation fourth quarter 2024 corporate update. My name is Cindy and I will be your conference operator today. All participants on the call portion of this webcast will be in listen only mode until the question and answer portion of this earnings call. If you would like to ask a question during that time, simply press star then the number one on your telephone keypad. If you would like to withdraw your question, simply press star then two on your telephone keypad. Please note this call is being recorded. I will now like to turn the webcast over to Dewey Stedman, head of investor relations at United Therapeutics. Please go ahead.

Thank you Cindy and good morning. It's my pleasure to welcome you to the United Therapeutics fourth quarter 2024 corporate update webcast. 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 these forward-looking statements. Also, today's remarks may discuss the progress and results of our clinical trials and 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 the products are available on our website. Accompanying me on today's call are Dr. Martin Rothblatt, our chairperson and chief executive officer, Michael Binkiewicz, our president and chief operating officer, James Edgemond, our chief financial officer and treasurer, Dr. Lee Peterson, our executive vice president of product development and xenotransplantation, and Pat Pazan, our executive vice president of technical operations. Note that Michael Binkiewicz and my colleague Carrie Silvers will participate in a fireside chat and -on-one meetings at the TD Cowan 45th annual health care conference in Boston on March 3rd. And along with Gil Goldin, our chief medical officer, I will be at the UBS European health care conference on March 4th in London. And finally, James Edgemond, Carrie and I will be at the Learing Global Health Care Conference in Miami on March 11th. Then our scientific, commercial, and medical fair scenes will present at the 20th annual John Vane Memorial Symposia in London on March 7th and 8th, and at the International Society for Heart and Lung Transplantation Conference in Boston on April 27th to the 30th. And now I'll turn the webcast over to Martin for an overview of our development pipeline and business activities. Martin?

Thank you, Dewey, and good morning, everyone. We have slides available for reference, and I encourage you to review those at your leisure. I'm not going to speak directly to the slides. Congratulations to the more than 1,300 Unitarians and to you, our shareholders, for supporting yet another record revenue year for United Therapeutics in 2024. In fact, 2024 was our third year in a row of record-setting revenue. This amazing performance was driven by our relentless drive to deliver patients with rare and underserved diseases a broad array of solutions to help them improve their lives. Beyond our stellar commercial performance, we have now begun our three-year cascade of clinical and regulatory events, starting with the recent IND clearance for our eukidney clinical trial. This trial is the first FDA-cleared, registration-supporting clinical trial of a xenoo organ and could provide an opportunity to put an end to dialysis for the hundreds of thousands of patients with end-stage renal disease who cannot qualify for a human kidney transplant or who have little chance of obtaining one before their health declines. We expect the first transplant in the middle of this year. Last month, we completed enrollment of the inhaled tricostinil Teton-1 study in idiopathic pulmonary fibrosis. We expect top-line data from the Teton-2 study in the second half of this year and Teton-1 top-line data in the first half of 2026. Tricostinil, which has been scientifically demonstrated to be anti-fibrotic, anti-proliferative, and anti-inflammatory, is far more than just a vasodilator. We believe its multifactorial mechanisms of action could be complementary to existing approved IPF agents and even to many of the potential IPF drugs in late-stage development. IPF is extremely hard to treat, but we are encouraged with the success we saw in a post-hoc analysis of IPF patients with pulmonary hypertension in the INCREASE study. Our goal is to bring this potential innovation to market as quickly as possible to patients in need of something additional to existing therapies on the market. And that's not all. We're tremendously excited for the potential of Rolinopag to be the first true -a-day oral prostacyclin agonist for pulmonary arterial hypertension patients. If successful, Rolinopag could fundamentally change the positioning of prostacyclines in the PAH treatment paradigm, potentially leading to the upfront use of prostacyclines in PAH. As an example of the potential for Rolinopag, Selexipag, a twice-daily oral prostacyclin agonist, logs more than $1.5 billion in annual U.S. sales. And this is for a twice-daily oral product with a dose ceiling, unlike Rolinopag. We expect to conclude enrollment in the Advanced Outcomes Study later this year, allowing for top-line data in 2026. Literature has long suggested that earlier prostacyclin use leads to better results. And a -a-day oral would complement traditional ERA and PDE-5 orals that PAH patients generally use for first-line therapy. Any one of these potential products, Eukidney, inhaled for prostenil for IPF or Rolinopag, could fundamentally change how patients with ESRD, IPF or PAH, respectively, are treated. And each represents a -billion-dollar revenue opportunity for us. We've posted record revenue performance, progressed several registration studies, and launched the first revolutionary trial of a xenoo organ. We remain focused on the needs of you, our shareholders, through a disciplined financial algorithm and capital allocation philosophy. In the past five quarters, we have touched on all three areas of our capital allocation philosophy across both our commercial and development portfolios. We've invested in CAPEX to support our new TIVASO DPI manufacturing facility and acquired additional real estate to support future commercial manufacturing needs. We also commissioned the world's first clinical-scale DPF in Virginia and plan to complete two others. On corporate development, we acquired IVIVA and Miramatrix to enhance our organ alternative development expertise. And we've licensed in new technologies to support our terprostenil business. And with all this, we still returned $1 billion to you, our shareholders, through an accelerated share repurchase program that was universally well received. We will continue to evaluate all three core areas of our capital allocation philosophy on an ongoing basis. Record performance, progress with our innovative and revolutionary development programs, discipline, financial management, and capital allocation. We've never been in a better position at United Therapeutics, and we're excited to forge ahead in 2025. And with that, I'll now turn the call over to our president, Mike Benkowitz, who will give an overview of our commercial performance for

the quarter. Mike. Thank you, Martine, and good morning, everyone. Today, as Martine mentioned, we are pleased to report another year of record-breaking revenue, driven by double-digit percent revenue growth for all our major revenue contributors, Tiveso, -from-Odulon, Oranitram, and Unituxen, leading to almost 24% growth over a full year of 2023. For the quarter, we saw 20% revenue growth from the fourth quarter of 2023 and saw record total terprostenil referrals and patient shipments, along with near-record total starts. Our fourth quarter total net revenue was down slightly sequentially, while our gross revenues for the fourth quarter was record-setting. The modest decline in net revenue is due in part to our recent contracting efforts for Tiveso, which I will discuss in a moment. Total Tiveso revenue for the fourth quarter was $416 million, a 19% increase over the previous year. This continued strong commercial execution in what is normally a seasonally challenging quarter was driven by record patient shipments and near-record referrals and starts, largely on par with the previous quarter. The sequential decline in Tiveso revenue from 3Q to 4Q was primarily driven by a larger -to-net deduction associated with our recent contracting efforts that we've been highlighting for the last few quarters. Our investment in these contracting efforts was conducted to help position nebulized Tiveso and Tiveso DPI at parity with current and potential future competitor products. As we have previously noted, these new contracts became effective over the third and fourth quarters of 2024, and we saw this impact primarily in the fourth quarter. At this point, we believe these additional investments and rebates have largely been pulled through, creating a new base from which Tiveso can continue to grow. Moving to our Renatram, we reported 28% revenue growth in the fourth quarter of 2024 to $108 million, largely in line with the third quarter of 2024 and again what is normally a seasonally weak fourth quarter for specialty pharmacy ordering. In the fourth quarter, we saw record patient shipments for our Renatram. Close to 50% of Renatram starts are now coming from remodeling transitions, indicating to us that our educational efforts around use with intermediate high-risk patients needing additional PAH treatment, along with scientific discussions about the expedite study, are influencing Renatram use. Moving to Remodeling, we reported fourth quarter worldwide revenue of $135 million, up 17% from the prior year period. In January, US revenue grew 11%, setting another record for patient shipments. We continue to see strong referral and start trends for Remodeling. In January, our partner DECA received FDA clearance for the new Remunity Pro pump. Remunity Pro is the next generation in subcutaneous pump technology, optimized and designed for patients with PAH. Remunity Pro builds on our unique Remunity Pump platform with features designed with input from PAH practitioners and patients to further simplify daily use. Compared to Remunity, Remunity Pro offers broader accessibility through intuitive technology and incorporates a touchscreen remote with -by-step guidance, streamlined alerts, simplified patient filling, and automatic pump-driven priming. We expect to launch Remunity Pro later this year. Finally, Unit-Huxen achieved record revenue of $68 million for the fourth quarter, up 25% from the prior year quarter. US revenue for Unit-Huxen was $62 million, driven by both price and volume increases. This growth demonstrates the product's strong market presence and the effectiveness of our commercial strategies. To wrap up, we are extremely proud of our team's accomplishments this quarter, as the underlying dynamics of our business remain very strong. And with the recent investment in our commercial contracting efforts, we believe we are well positioned to continue providing our important medicines to patients while delivering value to our shareholders. Martin, I'll turn things back to you to run the Q&A.

Thank you very much, Mike. Operator, please open the lines to any questions.

We will now begin the question and answer session. To ask a question, you may press star, then 1 on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star, then 2. At this time, we will pause momentarily to assemble our roster. Our first question comes from Roger Song of Jeffries. Go ahead, please.

Great. Congrats for the quarter. Thank you for taking our question. Maybe start with the top nine commercial franchise, given you don't provide the 2025 sales guidance, can we understand the growth trajectory for the year? Also, you mentioned some seasonality for Q, and then how should we think about this year in the upcoming quarters? I'm happy to answer your pipeline question. Thank you.

Thank you, Roger, for the kudos. I'll bounce that question to Mike.

Sure. I think as we think about 2025 and beyond as it relates to what we call our foundational business, which is our existing commercial portfolio of products, I think what we've been saying for the last few quarters, the last couple of years really, is that we expect to continue to grow double digits out into the mid-decade, and then obviously with expected real NPEG and IPF approval for Q, that growth trajectory should inflect in a meaningful way. So really, even with the contracting efforts we employed over the last couple quarters, or that went to effect over the last couple quarters, we really see no change in that perspective in terms of the base business for the next year or two years. So we're just going to continue to execute commercially and, like I said, deliver that double-digit revenue growth performance.

Perfect answer, Michael. Thank you. Operator, next question.

The next question comes from Jessica Fai of JPMorgan. Go ahead, please.

Great. Good morning. Thanks for taking my question. So with the first transplant for the eukidney clinical trial expected mid-year, can you talk about what you'll be looking for to support proceeding to the next transplant? I think there's a waiting period in between the first and the second. And then just talk about what proof points in that program would ungate larger-scale investment in additional DPS facilities. Thank you.

Thanks, Jessica. Nice to hear your voice this morning. And I'll flip that question over to Dr. Peterson, our EVP, Zeno. Great.

Yeah. Yep. Hi. Yeah. So as you mentioned, we have – this is a single phase-less study, and it starts with a cohort of six participants. And then we have a 12-week review period where we will be involving – well, we're actually involving our DSMB, which is our independent data safety monitoring committee, as well as our steering committee, throughout the study because it's open label. But we'll have a formal review of all of the data, safety data, and as well as patient and graft survival data at that point, and determine the risk-benefit ratio of going forward into the remainder of what we have planned of up to 50 patients. And as far as the endpoints or the demonstration of success, we're going to be looking again at a six-month graft survival rate, patient survival rate, as well as several parameters of kidney function, and then, of course, of safety, which includes transmission of infections, including potential zoonotic infections.

Lee, that's a great answer. Thank you so much. And, Jess, in terms of additional spending on DPF facilities, it's premature to speculate on that, but it will just be something that we'll consider as the trial proceeds. Operator, next question.

The next question comes from Ash Verma of UBS. Go ahead, please.

Hi. Thanks for taking my question. I wanted to understand how you view the Hyperion impact from WinRiver to your business. This study finished earlier than expected. And in the past, I understand that you've talked about that the WinRiver late line and the chemotherapy used with some of your products was kind of insulating your pH position. But now that WinRiver moves earlier line and faster than expected, can Typhus still grow on the pH side? Thanks.

Thank you, Ash, for dialing in this morning. Mike, I think that would be the best person to answer that question.

Sure. So I think in terms of the Hyperion study, I mean, obviously, we'll see how that plays out over the next couple of quarters. I remain, as I said in the answer to the first question, we still expect that we're going to continue to grow double digits across our franchise. I do not think, as we've said all along, WinRiver is not a cure. It's definitely in addition to the pH treatment armamentarium, which is great for patients. It doesn't replace prostacyclin. I think what we've seen up until now is it's being eased in combination with prostacyclin. I think that will continue to be the case if, for whatever reason, physicians start to use WinRiver ahead of prostacyclin over the long term. I think that's immaterial because pH continues to be a progressive disease and whether patients start on prostacyclin before or after WinRiver, eventually they're going to get to a prostacyclin. So as we kind of think about our business over the long term, we think that the impact is going to be, really be immaterial.

Excellent, Michael. Operator, next question.

The next question comes from Joseph Tome of TD Cohen. Go ahead, please.

Hi there. Good morning. Thank you for taking my question and congrats on the progress. Maybe another on the xenotransplant. Can you put into context the baseline disease severity of the first patient that will be enrolled, maybe as it relates to kind of the baseline disease severity of Tijuana Looney? And then related to that, we've obviously been able to follow these patients' progress through either press releases from the hospitals themselves or new sources. I guess, do you expect this to continue in the formal clinical study? As early as yesterday, it seems like Ms. Looney was able to return home. We can kind of watch this as it happens. So that can be the case in the formal study as well. Thank you.

Thank you, Joe. I think Dr. Peterson could give you a very good answer on that question.

Yeah. So I think your second question was about how we will follow our clinical study patients with regard to the news and what's been shown with Ms. Looney. We will not be doing that. For clinical studies, the data are...patient privacy, it will not be the same as what you've seen with this EIND case. It will be more like a traditional clinical study where you don't have names and you don't follow that. As far as the eligibility, our eligibility includes two populations of patients. One are patients who are not eligible for the current kidney transplant waitlist, but they don't have several comorbidities. They're not very, very sick patients, probably like you're asking specifically about the first two heart patients. Our patients won't have severe cardiovascular comorbidities as well as several other. But again, they won't be eligible for the list due to medical reasons. And then we also have a second population which probably Ms. Looney would fall into, which is that they are not expected to get an allo transplant due to things such as HLA sensitization or other factors, type O blood or a combination of these factors. They're not expected to get an allo transplant for at least five years. This is the second population where again, they're on the list, but they're not expected to have a good chance of receiving an allo transplant. I hope that gives you a little bit of an indication, again, in comparison to Ms. Looney where you've really been able to follow her status, which is really great. We're really, really happy to help patients like her. And probably the second category is very similar to of patients. It's very similar to what you understand and what we understand where she is.

Thank you, Dr. Peterson. Superb. 360 degree answer. Next question, operator.

The next question comes from Rowanna Ruiz of Lerink. Go ahead, please.

Great morning, everyone. So question about Tyveso in PH ILD specifically. Could prescribing growth on the ILD side plus increase in commercial volumes under Part D redesign possibly outweigh some seasonality trends from 1Q going to 2Q? Just curious if there's any color on that.

Very interesting question, Rowanna. Michael, can you answer that? Sure. I think in terms of the

first part of the question around PH ILD growth, as you recall, we expanded our sales force coming into 2024 really to try and drive the drive prescribing growth in the PH ILD or I'm sorry, in the ILD treaters, those physicians that are seen, the PH ILD patients. So prior to that, or at least at launch and up until then, I think what we were seeing is the vast majority of PH ILD patients were being referred to pulmonary hypertension clinics. And it was those physicians that were prescribing Tyveso. And so, but as you kind of think of the patient population, that really wasn't a sustainable model going forward if we really were going to have an impact and be able to penetrate the market. So that was really sort of the idea behind the expansion was to really start to continue to educate the ILD treaters on not only the disease, but how to use Tyveso, how to start to manage these patients. So I will say that that so far has paid off in spades. You know, if you look at our prescriber growth over the course of 2024, the majority of that growth is in the ILD treating community. So we are starting to get we're starting to get the breadth of prescribers in that group and then actually starting to get some end roads on the depth. I talk often about the three plus, you know, doctors that get to three plus patients, you know, then they quickly jump up to six, seven, eight, nine, ten patients. So we're having a lot of success both in terms of the growth, the breadth of the prescribers and starting to get to get more depth among those prescribers. And so I think we just expect that to continue as we move on to 2025 and beyond. And, you know, I was just looking at calculating if you look at, you know, patient growth between PHILD and PAH. The nice thing is with Tyveso is we're actually growing on both indications. And so in 2024, we grew roughly, I think, is about 37 percent, 35 to 40 percent in PHILD, still mid-teen growth in PAH. So it's nice to see that we're growing. We're growing in both indications. So I think hopefully that addresses the first part of your question around prescriber growth and then growth of PHILD versus PAH. As it relates to Part D impact, I think, as we said for the last couple of quarters, I think that largely played out last year. You know, as we saw in Q1, we saw more PAH patients or patient assistance patients convert over to commercial paying patients in Q1 of 2024. And then that continued over the course of the year. We kind of settled in at about, you know, about roughly 90 percent of our patients are commercial paying patients. And then 10 percent are in our, roughly 10 percent are in our PAH program. I would expect that that's going to be kind of the new normal or new baseline going forward. Could shift, you know, bounce around a little bit, quarter to quarter, just depending on the type of patient we're getting in. But generally I would expect to kind of settle in around that. So I'm not expecting to see much of an impact in Q1 or Q2 as a result of the Part D redesign.

Excellent. Michael, your encyclopedic knowledge is a benefit to all of us. Thank you so much. We really appreciate it. Operator, we only have time for one last question. And whoever that may be, maybe it'll be a question for our chief financial officer since this is a earnings call. Next question, operator.

Okay. The next question comes from Andres Argyris. Go ahead, please.

Thanks. Good morning. Thanks for taking our question. And Marcin, apologies. You put me on the spot on the financial question. I don't think I had that one teed up here. But first of all, kudos to the great year and also to the milestone on getting IED clearance. You know, you're leading the way. It's pretty fascinating and interesting going forward here. And following to one is progress here. Resume daily activities is kudos to the team. My question was really just quickly around TIEVASO and IPF, getting a sense of the intellectual property mode that you built around that, how long we can expect exclusivity, and then quickly on contracting and some of the competitive dynamics behind that. I don't know if I squeezed two in there, but apologies for that.

Yeah. Okay. Well, thank you, Andres. We appreciate your kudos. You're off the hook on the question for James. We don't really like to discuss publicly the issues relating to IP and whatnot. And we're about out of time. So I'm going to ask just Michael if he could talk about the contracting aspects of our anticipated launch into IPF. Michael?

Yeah. So, Andres, I'm not sure if the question was related directly to contracting and IPF or just contracting generally or what we've done thus far. But really, I think the philosophy that we and the strategy we employed last year was to start to lock in payers with some additional rebates in anticipation of future competitors. And then the idea behind that is if we start to have those rebate dollars flowing through, then regardless of where a potential competitor comes in with rebates, we have dollars flowing through. And so that puts us, I think, we think, in a stronger position. It keeps us at parity. I think payers will be less likely, more reluctant, to enter into contracts that would disadvantage us because at that point they'd basically be turning off the spigot of the rebates. So that was really the idea behind the payer strategy, which is get the rebates in place, start to get those dollars flowing, keep us at parity with competitors, and then we feel like if we're really, you know, and then have the discussion with the clinicians around what's the better product for their patients. And we feel very strongly that we're better positioned and very well positioned to succeed on that front.

Thank you, Mike. Perfect answer. Operator, you may now wrap up the call.

Thank you for participating in today's United Therapeutics Corporation earnings Webcast. A rebroadcast of this Webcast will be available for replay for one week by visiting the events and presentation section of the United Therapeutics Investor Relations Web site at .UNITHER.COM. You may now disconnect.