Great. Good afternoon, everyone. Welcome. My name's Jessica Fye, biotech analyst at J.P. Morgan, and we are continuing the 43rd Annual Healthcare Conference today with United Therapeutics. For the first part of our session, you're going to hear a presentation, and for the second part, we're going to get into some Q&A. If you want to ask a question, you can raise your hand, and I'll bring you a microphone, or you can send me questions on the iPad up here. But with that, let me pass it over to United's Chair and CEO, Martine Rothblatt.
Thank you, Jess. Thank you, everybody, for attending. At United Therapeutics, our tagline is "Enabling Inspiration," and I think that's probably driven by our company culture, which is focused on providing every person who works at United Therapeutics, whom we call "Unitherians," with the best possible career development of their life, and it keeps the people super motivated, love working at our company. We actually have the lowest voluntary turnover of any biotech company that tracks those metrics publicly, so I think it's a really good sign that we have successfully enabled inspiration. This is our standard safe harbor statement. I'll leave that up for you to look at for a moment, but while you're doing so, let me point out our deal books. We have a very active business development group at United Therapeutics. In fact, our head of business development, Dr.
Eades is sitting right in the front row. One of my favorite deal books is the one all the way on my left, the acquisition of Revivicor, our xenotransplantation company, and the logo on that deal book is a pig with wings. It shows even lawyers can have a sense of humor. Our company was started to save my daughter's life. That's myself, my partner, and our daughter. Our focus is to concentrate on rare lung diseases. She has a rare lung disease, pulmonary arterial hypertension. Along the way, people were impressed with our success, and the National Cancer Institute asked us to take on a rare oncology product, Unituxin, for neuroblastoma. With that biologic, we were able to save the lives of half of the kids that are diagnosed each year with neuroblastoma. That's about 500 lives saved a year.
In addition, if you have pulmonary arterial hypertension, as my daughter does, the only cure for that is a lung transplant. Because there are so few lungs available, for example, about 3,000 lungs each year are transplantable and transplanted, whereas about 300,000 people each year die of end-stage lung disease, we undertook the mission to create an unlimited supply of transplantable organs, starting with the lung, and then we moved on to the kidney, the heart, and the liver. At United Therapeutics, we are in the midst of experiencing three different waves of growth. Our first wave is what we call our foundation wave. With this foundation wave, we have a number of FDA-approved products, which are creating a robust cash-generating commercial business. Our second wave is what we call our innovation wave.
Here, we have a cascade of clinical and regulatory events over the next three years, with the potential to expand our current business at least twofold, and here I'm referring to clinical trials of a once-daily pill to treat pulmonary hypertension, which seems to be the most potent type of oral therapeutic there's ever been, as well as a brand new treatment for pulmonary fibrosis, which will hopefully be able to halt the progression of that fatal disease, then there is the revolutionary wave of our growth. This is what we refer to as our business of creating an unlimited supply of transplantable organs: first kidneys, moving on to hearts, livers, and lungs. That too, that organ business, because there is such a huge unmet need for transplantable organs, we believe that organ business, the revolutionary potential of it, is double even what we'll achieve in the innovation business.
Right now, as this chart shows, we are at around $3 billion a year revenue run rate on an annual year-over-year growth rate heading toward $4 billion a year. We believe that our innovation phase will double that to an annual revenue run rate of at least $8 billion a year. Then our revolution phase, where you're dealing with a horrible toll of end-stage organ disease, 500,000 people with kidney failure that are not even on the transplant list, and then it goes on and on from livers, hearts, and lungs, we think we'll double that $8 billion revenue run rate to around $16 billion a year. Let me identify some of the near-term news events. It's really amazing because in 2025, I actually can't remember a year when United Therapeutics has more high-impact news events queued up.
As shown in the slide, we expect to have our IND clearance for our UKidney. This is a 10-gene modified xenokidney, and it would be the first FDA clearance for a xeno organ IND ever. So that will be truly historic. That's one thing that we have queued up for approval. The IND was recently filed with the FDA. Secondly, one of our other organ products is one that has increased by 500 the number of transplantable lungs using a technology we call CLES. And we filed that PMA with the FDA. We are hoping for that to also be approved in 2025, which would be another major news event. It was really amazing. Earlier this year, we had a celebration of the 500th successful lung transplant that we were able to enable.
One of the patients got up and spoke, and she explained how, because she was only 60, she had nevertheless aged out of being able to receive a donor lung through the normal United Network for Organ Sharing transplant process. But the doctors said to her if she was willing to take one of our pre-PMA-approved lungs, that she could still have it even though she was 60. And she asked, she's not like a PhD scientist, she said, "Well, what do you mean by one of these kind of CLES or EVLP?" She said, "Ex vivo lung perfusion." They explained to her, "It's an ex vivo lung perfusion lung.
What do you mean by ex vivo lung perfusion?" And the doctor said to her, "Well, it basically means that the donor lung is washed before it's transplanted into you." She said, "That sounds better to me." And indeed, it worked out very well, and she's gone back to her hobbies with her and her husband sailing in the Chesapeake, and it's been an excellent story for her and hundreds of other lives saved. Another big news event for this year is the unblinding of our TETON 2 data in idiopathic pulmonary fibrosis. TETON 2 is the name of our phase three registration clinical trial for that indication using our medicine called Tyvaso. So that data is from a trial which was completely enrolled last year, and the data will be unblinded and made available to everybody in the second half of this year.
Another big milestone is once the FDA clears our IND, we will then announce our UKidney studies, FPFT. That's the first patient, first transplant. And many of you are probably aware from New York Times and the broadcast news that we already have living patients with the xenokidney in it. One I'll show a picture of shortly, Tawana Looney. However, those are what are called by the FDA compassionate use transplants. And this is the first patient, first transplant actually in the clinical study. In addition, from our Miromatrix subsidiary, we expect to have data in the first lab-manufactured kidney, I mean liver, lab-manufactured liver used to save a person's life. This is called our miroliver ELAP study. There are a number of major hospitals, such as the Mayo Clinic and others, that are participating. And we expect the first patients to be treated with the miroLiver liver.
It's the first time, by the way, that the FDA has ever approved a clinical trial of an organ manufactured in a laboratory to try to save somebody's life, so we're super excited about that, and then last but not least, our advanced outcome study will close in pulmonary hypertension. This is the study of our once-daily pill for prostacyclin. Seems to be the most potent prostacyclin available for pulmonary hypertension, and that will then start a clock, a six-month clock running until 2026. As you can see in the next block, it says Ralinepag, NDA for PAH, well, Ralinepag is the name of the drug that's being tested in the advanced outcome study, so those two last rows in the 2025 and 2026 box go together.
I won't read every single line on the slide, but I think you can see that United Therapeutics is chock-full of news flow for 2025, 2026, and 2027. I'm also very, very proud that we've been able to accomplish all of this growth, all of this innovation, and all of this revolutionary potential, all with a solid financial foundation. We've had nine consecutive quarters of double-digit year-over-year quarterly revenue growth, three years of double-digit annual revenue growth, and a 23% cumulative growth rate since our first approval. In addition, we're bringing in over $1 billion a year in operating cash flow. And in fact, everybody is in agreement that we are the most profitable biotech in our space, so that's really super.
And we've been able to share that good news multiple ways with our shareholders, not only through our stock price, as referred to previously with the CAGR, but also by returning $1 billion directly to the shareholders with an accelerated stock repurchase plan last year. Our best-selling drug is called Tyvaso, and it is in fact now the most prescribed prostacyclin in the United States. Another drug I'm very excited about and proud of is Orenitram. Now, that's not only because if you look at that brand name carefully, you'll see it spells my first name and the first two letters of my last name backwards. But it is a really much-beloved pill taken by our patients and probably the easiest way to treat one's pulmonary hypertension with a prostacyclin.
And then we have a very important medicine, Remodulin, that has really seen continued growth in very large part to a revolutionary new type of parenteral Remodulin pump invented by the most distinguished gentleman sitting in the front row here, Dean Kamen. Dean, can you please stand up and just take a bow? Thank you. Now, in terms of innovation, this being above our foundation level, we've got these new trials going in pulmonary fibrosis. As many of you are, I'm sure, aware, pulmonary fibrosis is a fatal diagnosis. It is the cause of actually more lung transplants than pulmonary hypertension. There are two medicines approved for it, but neither of those medicines either halt or improve the degradation in the patient's forced vital capacity. So we're hoping that Tyvaso will show a better job for these patients than the current drugs.
And it's being tested both in naive patients, in other words, patients not currently taking one of the two approved drugs, as well as patients who are taking one of the two approved drugs. It's being tested on top of that. So if we can get that drug approved, then it'll be very beneficial in terms of its market penetration, that physicians will not have to remove a patient from something they're already taking. Even if it's not reversing their disease, it might be slowing the disease down so they could take that drug and take our drug on top of it. Actually, polypharmacy seems to be the way of the future in a lot of these orphan diseases.
More and more, physicians are looking to undertake what's called a four-corners approach to rare diseases, where they're looking at one, two, three, four different modalities by which these complex diseases progress in patients and have a specific drug for each of the different pathologies leading to this four-corner approach. And once you have a patient on three or four drugs, then the next goal is to de-escalate therapy. De-escalate therapy does not mean to let the disease progress through one of the four different pathways or three different pathways, but instead give them a gentler treatment. So for example, de-escalate a parenteral therapy to an inhaled therapy, or de-escalate an inhaled therapy to an oral therapy, or de-escalate a three-times-a-day oral therapy to a one-time-a-day oral therapy. This is the physician mindset nowadays.
Now, a lot of people are curious about, like, how did United Therapeutics get started on this great platform of therapies for Remodulin, Tyvaso, Orenitram? Well, we really owe it all to the scientific founder of the company, the Nobel laureate, Sir John Vane, who chaired our scientific advisory board right up until the end of his life. He was the top pharmacological chemist at the Burroughs Wellcome Company and the Wellcome Trust. Absolute genius in chemistry and always identified the mechanisms of action of the different new molecules that he would synthesize. So in his early publications, going back to the early '90s, when he synthesized and obtained patent approval for treprostinil, he noted that it had multiple different mechanisms of action.
The one which is most salient to pulmonary fibrosis was its antifibrotic properties that have later been validated in in vitro assays, in addition to Sir John's original pioneering work. But in addition to that, he noted that treprostinil had these vasodilative properties, these anti-proliferative properties, and these platelet deaggregating properties. In addition to all of that, he noted and again showed with different types of cell populations, cardiac cell, cardiac myocytes, that it had inotropic properties, which have subsequently been validated by many other clinical investigators. So our current bringing forward of its antifibrotic properties is just a continuation in the validation of what Sir John Vane identified back in the 1990s, shortly after winning the Nobel Prize for his work. Now, the next drug that's in our innovation platform and potential to double the value of United Therapeutics is Ralinepag.
As noted in this slide, this product could be our first once-daily prostacyclin. This slide kind of looks a little bit like a subway map, if any of you have ever ridden in the New York subway system or another one. On the vertical axis, what we show is how many times a day you have to take something. It's kind of like how many transfers you have to do to get to your destination. Down on the x-axis is an indication of what year something was brought into being, kind of like which year a station came into operation. You see, like when we have our continuous products, our parenteral products, you got to take them continuously, which means a lot of stops. You're on the local.
Later on, we got developed a nebulized Tyvaso, and now there are only four stops to make to get to your destination. Then came Orenitram with three stops, maybe two, depending on your timing. And then most recently, we hope that Ralinepag will be approved in 2027, and that would give you a single stop to your destination. The next slide shows our different platforms for our organ manufacturing. Remember, this is the revolutionary wave of United Therapeutics. We have a lot going in our organ manufacturing space, and it is kind of a good exemplar of our statement at UT that we always like to have multiple shots on goal. We've got four different technologies underway that fall into the category of bio-artificial organ alternatives. We have three different technologies underway for xenotransplantation and one each for regenerative medicine and 3D autologous printing.
The 3D autologous printing, because that's kind of one that might not be immediately obvious, what does that mean? Autologous means that the organ is cellularized with your own cells, cellularized with your own cells because your blood, the patient's blood is apheresed. CD34 cells are then reprogrammed to be inducible pluripotent stem cells or iPSCs. Those are then differentiated in different media to different types of specific organ cells, like airway cells and vascular cells. And then billions of such cells are then streamed into a 3D printed scaffold, which is the shape of the organ. At the end of the day, you could have an organ transplant that matches your DNA, and no immunosuppression would be required. We are rapidly progressing on this revolution that I've described.
Perhaps the most exciting recent news is that we completed a transplant on November 25th, 2024, that has been really life-saving and life-validating to its patient. She was discharged on December 6th, 2024. And here you can see in this picture how well she's doing. There's me and my partner, Bina, and the patient, Tawana Looney, is in the middle on my right, and her husband, Mr. Willie Bennett, is on her right. If you look very carefully at Tawana Looney's shirt, she's wearing a little yellow pin. And we at United Therapeutics, we issued those little yellow pins to commemorate my daughter's 40th birthday because nobody thought that she would live to be 10, much less 20, 30, or 40. And she's proud to share with people that to her knowledge, she's the longest living patient with pulmonary hypertension.
We started on our quest to develop xenografts by trying to develop a xenolung to save my daughter and other people with her condition's life. As it turns out, the medicines work so good that fortunately our daughter has not required a lung transplant. That effort to develop a xenolung culminated in a xenokidney that has saved Tawana Looney's life. When Tawana heard that story, she was so proud. She felt like she'd caught a baton from my daughter in a relay race over the decades and proudly wears her 40-year pin wherever she goes. We want to make sure that we can help many patients in addition to Tawana. We've built the first clinical-scale xenograft production facility in Christiansburg, Virginia.
Its formal name is the Honorable Louis Sullivan and Honorable Tommy Thompson Clinical Xenotransplantation Facility in recognition of the great contributions those two secretaries of health and human services accomplished to broaden awareness of the need for organ transplantation and improve the organ procurement and transplantation network. So that facility has a capability of producing about 200 kidneys and 100 hearts per year. We have now broken ground and excavated away the second such facility, which will double our capacity. It's right across the highway from the Mayo Clinic in Rochester, Minnesota. And we've now also signed all of the paperwork to complete construction of a third DPF right outside of the Houston Medical District, one of the largest complex of transplant hospitals in the U.S. So combined, we'll be able to help hundreds of patients a year upon FDA approval.
United Therapeutics is uniquely positioned to help patients and create lasting value. We are a public benefit company, which means that when our patients succeed, we all succeed. We've got the cash flow and innovation spree to core to build upon a foundational wave into an innovation wave, and then a revolutionary improvement in the healthcare therapeutics available to end-stage organ disease patients. And finally, just for those of you who like to focus in on the very near-term results, we have 36 months coming of lots of results almost every quarter, sometimes twice a quarter. No other biotech has this compelling profile. Thank you very much. I'd now like to call up to the podium to join me to answer any questions, our Chief Financial Officer, James Edgemond, and our President and Chief Operating Officer, Michael Benkowitz. So I'm happy to take any questions for Michael or for James.
There's a roving mic if you want to raise your hand to get the mic. And there's a question in the front row.
Born in Westmark, Copenhagen, Denmark. Congratulations, first of all, on all the success. I was very happy personally when I saw that you entered into IPF. We're doing a lot of IPF biomarkers, and that leads me to my question. How are you assessing the antifibrotic effects you see in your IPF studies? Are you doing any serological assessments of that?
So the question is, like, how are we assessing the antifibrotic effects of Tyvaso in these patients and what type of serological studies have we performed? The data on the antifibrotic properties of Tyvaso, some have been published, others we've done internally, which will go into our filing across every finger that I can cross for the IPF study of nebulized Tyvaso. More than what I said in the opening presentation about the data tracing back to Sir John's original publications, I cannot say right now, but I will say that these studies are enrolling quite rapidly. And what we've generally seen at our company and I think a lot of our peers is when physicians have strong belief in the mechanism of action, they tend to kind of enroll a study a little bit more quickly than when there's a lot of skepticism about the mechanism of action.
Unfortunately, I don't have a very concrete question to give you on serological assay results, but I can say that the studies have enrolled briskly. I didn't really mention that we're doing two studies. That will gain us European approval, which is required for approval in the EU. And the first study will read out the second half of this year. The second study will read out in the first half of 2026. Thank you. I know Jess always has a question.
I can go. So first off, congrats on getting the IND in for UKidney. Can you help us think about what that development plan looks like once you presumably get it cleared and actually can formally go into the clinic?
Yes. So I think that's actually. I'm going to answer part of the question because I think that's actually the easier part of the development plan. And the more challenging and frankly, for me, even more exciting part of the development plan, I'll let my colleague Michael Benkowitz address, which is the scale-up and introduction of a very novel therapeutic into the healthcare system. So I'll be able to be very specific at next year's J.P. Morgan conference because by that time, the FDA will have cleared our IND, and I can speak concretely and definitively about exactly what is the protocol that is approved. However, there's a few things that we can feel pretty comfortable about from our interactions with the FDA. First and foremost, the most important things to the FDA are safety and efficacy, which is no different than it would be for anything else.
We only got to be able to file this IND because we had engaged in a multi-year INTERACT process with the FDA, and pursuant to the INTERACT process, they had defined for us a set of IND-enabling studies that had to be done under good laboratory practices with baboons using the 10-gene kidney. And we accomplished all of those IND-enabling studies, and the FDA seems quite satisfied that we accomplished them in accordance with their expectations. Now that gives you like a baseline sense of comfort in terms of safety and efficacy in a non-human, which is, you know, as an animal model, that's the best you can do, but now you've got to go into humans, so I think it would be a kind of a logical protocol to say this should not be a placebo-controlled study with mock surgeries that would make no sense at all.
So I believe it's going to be an open-label study. The impact of these xenografts should be dramatic enough that the numbers required should be relatively small. This isn't going to be a very large study. Like, you know, we think of hundreds or thousands of patients. I think it's reasonable to think that a rational size for a study like this would be, you know, some number of double digits of patients would give people, you know, reasonable comfort that it was safe and efficacious. And then you could talk about the duration until you see the endpoint that the FDA desires. The FDA is acutely aware of the terrible shortage of organs there are for transplant.
No organ is actually in which there is a greater gap between the supply and demand than for the kidney, with approximately a million Americans with end-stage renal disease and only about 30,000 kidney transplants being able to be performed each year. So I think the FDA, you know, wants to make this therapeutic available to patients as soon as possible, but not sooner than, you know, they have reasonable evidence of safety. So I don't think, I think you're going to want to follow these patients indefinitely for years into the future, but I think a reasonable kind of endpoint would be something that was measured in, you know, some number of months rather than talking about multiple of years of an endpoint. So I think, Jess, those are the kind of parameters that we could reasonably expect.
Now, upon getting approval and to carry out this type of a protocol, it should not take us beyond, you know, from enrollment and executing it, and it, you know, remains to be seen exactly what the FDA will be satisfied with. I think you're looking at something like a three- to four-year timeframe for the entire execution of the clinical trial program. So upon approval, how does one grapple with 500,000 Americans on dialysis, 10% of whom, roughly speaking, and it depends on exactly their comorbidities and age and so on and so forth, 10% of whom die each year. That's 50,000 people a year, plus or minus. All of these are the patients not even on the transplant list, so they got no hope of a transplant. How do you provide enough organs to satisfy this demand?
It's on that note, I'd like to pass the mic to my good friend Mike.
Gosh, thanks, Martine. Well, as you can imagine, as Martine said, with 500,000 dialysis patients not on the transplant list, you know, practically speaking, I think our commercial opportunity is going to be rate-limited by the number of organs that we can supply each year, and so Martine said in her presentation that we have one, what we call a clinical-scale DPF that opened this year in Christiansburg. We have two more that are slated to open before the clinical trial will be completed, and so each of those are capable of producing about 125 organs per year. And while we say that they're clinical-scale DPFs, they actually can provide commercial organs, and so, you know, upon launch, we will have, you know, some supply of organs that we can make available for kidney transplant patients to get things going, you know, coming right out of the gate.
In the meantime, we do have plans. We have had discussions in the process of starting construction on what we call a commercial scale xenotransplantation manufacturing facility that would be capable of producing or populating, housing 2,000 product pigs per year. And so, you know, those discussions, what we've really tried to do on the scale-up with that facility is make sure that we don't get too far out in front of the science. And so we're really trying to pace the spend and the construction of that facility with what we're seeing in the clinical trial. And so, you know, as we continue to, you know, really be thoughtful about how we pace that out, the idea is that we would have that facility come online at around the time that we would expect to have an approval for the UKidney.
And then initially, we could use, like I said, the clinical-scale pigs to supply organs. Those facilities would probably turn into what we call breeder feeder facilities for the larger xenocommercial manufacturing facility. And then as demand grows, we would continue to add more facilities over time. So, you know, it's a high-class problem to have in that there's a huge opportunity out there. As I said, we're going to be kind of rate-limited by the number of organs we're able to produce, but we feel like we've got a really good plan to scale up in the short, medium, and long term to help as many patients as we possibly can.
Perfect, Mike. Thanks so much. Thank you, Mike. Next question. We have somebody with a microphone there in the center aisle. Jess, I know you have another question queued up.
I guess I'm sort of curious with the company has a healthy cash balance. It's generating a lot of cash. You've got this kind of staged CapEx investment to support organs, and you also did what I think a lot of people in the room would agree was like a very successful accelerated share repo last year. So are we at steady state now between kind of like CapEx and cash generation, or is there the possibility, do you guys think about doing that again, just given what it did for stock price and some of your shareholders and stakeholders?
Thanks, Jess. That's a great question. Fortunately, we have on the podium my choice for world's greatest CFO, James Edgemond, and James, that would be squarely in your bailiwick.
Thank you, Martine. Jess, thanks for the question. I saw where this one was going to be directed. Let me just frame, if I could, our capital allocation kind of priorities that we've talked about before and then kind of circle back to your question. So for those listening, we have internally a capital allocation kind of philosophy in Waterfall that has been consistent and will remain consistent. So we first want to invest in ourselves and then invest in our facilities, and Michael talked about some of the facility aspects, and there's actually other facilities in terms of a manufacturing plant in North Carolina for Tyvaso DPI. So there's ongoing construction projects. The second capital allocation priority is going to be corporate development.
I think if you looked over the last 13 months, we've actually brought into UT two organizations more on the organ alternative and manufactured organ side, being IVIVA and Miromatrix. So we were glad to welcome them to United Therapeutics. The third item in our capital allocation priorities is return cash to shareholders. As you alluded to, we did a $1 billion ASR last year at the end of March that completed towards the end of the third quarter in September. Over the last 13 months, I think we've actually executed every pillar, every kind of step in the waterfall successfully. What I would say internally is we do debate these quite often in terms of finding the highest and best use of cash for shareholders. We want to make sure we're doing it in a thoughtful, highest priority way.
So I won't commit today to doing another share repurchase, but I want you to know it's in things that we discussed and topics we discussed in terms of trying to do it very thoughtfully. And we're going to continue to do that going forward, even considering what we still expect to be a lot of cash generation from operations. So no commitment, but I think we're going to continue to evaluate and apply that waterfall going forward.
Thanks, James. You know, you reminded me when you described our ASR that I mentioned at the beginning of the talk that one of our mantras at UT was enabling inspiration, and I think we've done that very well in terms of that you could see that in the statistics of our voluntary turnover. Another of our mantras that we use to guide ourselves in which products to develop is approve and then improve. In other words, there's all of these new medicines and technologies. You can always make them better and make them different, but what we try to do is focus on first getting something approved so we could start helping people as a PBC, and then we improve upon it.
The third mantra, which we owe to Mike coming up with, or at least imbuing us all with, and I think was very well exemplified in the ASR, is go big or go home. Next question. No more time. Oh, well. Okay, so unfortunately, you don't have to go home, but remember, go big. Thank you.