Thanks for joining us. It's a real pleasure. So I wanted to understand the United Therapeutics story a little bit in more detail today in the fireside chat. We have 25 minutes, and ask more questions about the manufacturing with which you are the closest to in the organization. So would love to get your perspective. Maybe perhaps we can start off by just getting, like, a high-level background about United Therapeutics for investors that might not be familiar with it.
Sure, sure. So I'd like to thank UBS for having us down here. Before I go into any details, I just want to mention that some of my answers today may have some forward-looking statements, and I would refer the audience and any listeners to our SEC filings, 10-K, and 10-Q, for any risks or precautions related to our business. So United Therapeutics is now 27 years, 27 years old, and it was founded by parents seeking a cure for a disease that their daughter had, which was Pulmonary Arterial Hypertension. And of course, this is back in the mid-1990s. And there weren't a lot of products available to treat this disease, and they took it upon themselves to seek a cure.
Today, 27 years later, we have six products, five of which treat Pulmonary Arterial Hypertension, one of which treats a pediatric oncology disease, neuroblastoma. We've reached approximately a $2 billion revenue rate annually. However, with all of that, we still don't have a cure, and the only cure today for PAH is a lung transplant. Hence, the reason we have embarked upon a program to provide transplantable lungs to treat PAH and cure it. We've expanded that now to not only include lungs, but hearts, kidneys, and even livers. In our earnings call last week, we talked about three waves of growth that we expect to see in the next 10 years.
The first wave will be driven by our current commercial products, with their continuing growth in the marketplace. The second will be driven by our TETON clinical studies, which are covering various forms of pulmonary fibrosis, and the outcome study with ralinepag, which will be used to treat PAH. Now, we expect the initial TETON study in IPF to fully enroll by the end of 2024, and we expect to see data from that study by the end of 2025. It's about the same for the outcome study with ralinepag. Assuming positive outcomes with those studies, and we remain very optimistic that those will yield positive results, we expect our revenue to grow to $8 billion upon approval and a launch of those products.
Then the final third wave of growth will be with our organ programs, which is currently really being led in the xenotransplantation area with the kidney and the heart. That will provide additional growth at around the 10-year period, we expect. You can see we're a pretty unique story, and we remain really excited about the future.
Great. Great, thanks for that background. So maybe I can start off, you know, like earlier in the year, I mean, one of the big surprises that we saw was your announcement that you want to get to more than $4 billion run rate by the end of 2025. That's something that has surprised a lot of investors, and I feel like the sell side, at least, like based on if you look at consensus, if that is even a reliable metric, it's not there yet. I think we are at around, like $3.3 billion. So, like, where is that growth going to come from? It's a pretty short timeframe to get that type of a ramp-up, and how much does Tyvaso play a part in this growth profile?
Yeah, sure. It's a great question, and I'll provide some additional detail on how we expect to get there. So first, to clarify for everyone, we're looking at a $4 billion run rate. So what we expect to achieve by mid-decade is our first quarter with $1 billion of revenue. So that's what we're working towards. Now, if you look at our current commercial products and what we expect to see over the next few years, so we have Remodulin, which we believe will remain flat. Orenitram and Unituxin, we believe will continue with single-digit growth. And then Tyvaso, we expect to see strong double-digit growth. Now, if you take all those and extrapolate them out to mid-decade, you get to, say, approximately the $900 million mark per quarter.
Now, how are we going to get to that next level with $1 billion? So over the last year, we've significantly increased the amount of people we have in the field, and that includes salespeople, medical liaisons, scientific liaisons, and nurses. And the result of that is we've more than doubled the amount of Tyvaso prescribers in the last year. Many of these prescribers are ILD doctors, and as we look at the health of these prescribers, currently over 40% of them have three or more patients that they're prescribing for. What we've also seen with the ILD docs is they are now themselves prescribing Tyvaso to treat ILD instead of referring those patients to a PAH doctor.
Of those ILD docs, 20% of them now have three-plus patients. So a lot of, a lot of great movement in that area, and we expect that to continue. So that's how we believe we're gonna get to the $4 billion run rate.
Great. One of the things, like, about this Tyvaso franchise, the transition towards the DPI is something that has surprised a lot of people. I think, like, when it was launching, you had given guidance sort of like a soft outlook that you expect to get, like, a 50/50 split in the long run on both indications. And by our math, like, we think that you're already there, and you have surpassed that level in terms of how much use is coming from DPI versus nebulizer. So, like, first, I wanted to just, like, get your thoughts on that piece. Do you think that there is more room to grow on the DPI conversion, or are you capturing new patient adds that is driving the good growth of the nebulizer?
Where, where can this eventually settle in terms of the split of the franchise?
Yeah. So I think, for those that looked at our third quarter earnings, they saw for the first time that we broke out DPI numbers versus nebulized. So you were able to see in detail how those are split in total together. So right now, we're at about a 60/40 split, with favoring DPI over nebulized. Now, it's important to note that we believe nebulization is always gonna have a role in treating both PAH, PH-ILD, and hopefully, in the future, pulmonary fibrosis. And the reason why is the nebulizer, even though it's more bulky and inconvenient for the patient, actually offers a lot of flexibility in the treatment paradigm. So HCPs can dose in one breath increments.
When you're treating these patients, there's a lot of subjectivity. So it allows them to really tailor the treatment to the patient. We think it's a really important tool that they have available to them. And of course, we have DPI, which has the convenience of being able to carry it in your pocket. But the dosing for DPI is in three breath increments. We have multiple ways in order to attack these diseases, and we think that's a great spot to be in.
I mean, as you head into, like, 2024 and 2025, and the co-pays normalize on, on the, you know, DPI versus the nebulizer, do you, do you think that can drive more of an inflection, in the conversion?
Yeah, certainly, it could. And while we're talking about that, we expect... And I'll remind everyone, Orenitram and Tyvaso DPI are both Part D reimbursed, whereas Tyvaso nebulized is Part B as a device. So they'll be impacted by some of the changes that are happening with Medicare. And of course, you know, we view anything that's gonna reduce the burden, pay burden on the patient to be a benefit, and that's a positive. So as we move into 2024, we'll start to see some of these changes take place, and some rebates will start happening as they move to eliminate the catastrophic limit.
Yeah. Yeah, that's great. And so I think this, look, I mean, it's definitely helpful to see the split of revenue coming in from DPI versus nebulizers. I mean, the other way to split this, obviously, is like, look at how much of it is coming from PAH versus PH-ILD. I know you haven't quantified that specifically, but I’ve got this message from the recent calls that you are trying to transition more of, like, a growth profile in PH-ILD, and that's a big untapped market. Anything that you can provide, like, qualitatively, quantitatively, in terms of, like, where is the split right now across these two products, and eventually, where can we see that go?
Yeah, I think, you know, on a granular level, we're just not ready to go there yet. But what we can comment on is much of the growth with Tyvaso is gonna be driven by PH-ILD, really in the near to midterm. And of course, with the potential positive outcomes of the TETON studies, that'll continue to drive growth as well. So, you know, it's gonna lean heavy probably on ILD, as you see those numbers increase. But as far as patient splits, I you know, I don't think we're prepared to really go into great detail there.
Got it. Okay. I mean, one of the things that we have been trying to assess is the impact of, you know, the supply here. And it's a nice problem to have when you have demand outstripping supply. But I think you have several measures in place to try to resolve that. So, like, can you explain to us just on a high level, so you got the MannKind first expansion of the facility come online already in June, I think, and then, like, you have another one coming in next year.
Mm-hmm.
And then you have some other in-house measures that you are tackling to expand more of capacity?
Yeah. So we, due to the time constraints of the earnings calls, we haven't been able to provide a lot of detail related to this, but I can certainly go into greater depth now. So there's been multiple efforts that have taken place, really, culminating in 2021 with the ILD approval. And this was pre-approval of Tyvaso DPI. But once we gained approval to treat ILD with Tyvaso, we immediately moved to make some pretty significant capital investments in the MannKind facility to increase their capacity for future production. Now, those investments involved purchase of high speed and high capacity equipment to produce the dry powder product.
Now, that equipment is very specialized and has a very long lead time, and we knew it was gonna take some time to get it built and get it in place. Now, in the meantime, while we were waiting for that, we did get approval of Tyvaso DPI, and we launched it very quickly after approval. And again, we recognized immediately that the interest in the product and the uptake, which was very strong, we were very pleased with, was going to require us to make some interim changes at MannKind to make sure we could supply the specialty pharmacies with their minimum inventory levels.
And so we did that, and we were able to double really on the bulk side, the bulk powder side, we were able to double their capacity and implement that in Q2 of this year. And the result of that is we've strengthened inventory levels and really addressed that concern. And now we're moving into trying to smooth out shipments and order frequencies with the SPs. But in parallel with that, of course, the equipment that we purchased 2 years ago is now in place and is being qualified at their facility. And we expect that to come online in, say, the next four-six months.
At that time, once that's done, we'll be able to support 25,000 patients out of the Danbury facility. So all that's happening in the next, say, 4-6 months, we'll have that capability. Now, beyond that, of course, we have to prepare for TETON outcomes with pulmonary fibrosis. Now, these studies could bring upwards of 160,000 patients into use of Tyvaso DPI or Tyvaso nebulized, which is a significant increase over what we have today. So in preparation for that, we have begun construction of our own facility in, on our North Carolina campus to support those additional patients. So design has been completed, and we expect to break ground on that early in 2024.
Now, that's gonna be a two-year build, and at which time we'll be able to do the work to qualify that site with FDA. And beyond that, really, it gets the schedule gets to say a little squishy beyond that. But preparations are already taking place to be ready to support pulmonary fibrosis-
Yeah.
in both forms.
When you get the expansion from MannKind early next year in this 4-6 months time frame, like, would that start to reflect in Tyvaso numbers right away, or is there any kind of like a lag effect from that?
I think it'll be fairly immediate. They're gonna be able to produce a lot of product very quickly, and that's helpful as we continue to grow the business in ILD and educate ILD prescribers on the benefits of Tyvaso.
Great. So, there are a few competitors emerging in PAH and/or PAH-ILD, depending on how you look at it. I just wanted to get thoughts from your vantage point, like, you know, more treprostinil is something that comes up in the investor debates a lot. Have Insmed and Liquidia potentially also becoming competitors in the near term.
Mm-hmm.
Like, how, how do you kind of, you know, plan your business to overcome those competitive headwinds? And what, what is right now you're thinking on where and when you might see the impact to what side of the business on Tyvaso?
Yeah. So I think in general, I'll go into each of those individually. But in general, we're used to competition. And today, there's over a dozen products to treat PAH, and Remodulin is a good example, approved in 2002, and still going strong today. And a lot of that has to do with how effective the product is and the support we provide patients. So we know how to deal with these markets. Now, Liquidia, we know, has a version of an inhaled version of treprostinil that they intend to market at some point.
Now, we believe in our own product, and I think, you know, some of the feedback we received during the BREEZE study, 98% favorable reviews of that product by the patients in the BREEZE study. Today, we've treated over 4,000 patients already with Tyvaso DPI. So we've had great success, great feedback from the marketplace. The patients really like the product, and we feel pretty good about it. The benefits of it is it's a single cartridge dose, so the patient will load the device with a cartridge, and they inhale it, and they're done. And they do that four times a day. The device does not need to be cleaned. You can carry it in your pocket. In fact, I have one in my pocket. And you can see pretty easy to use.
Open it up, here's the cartridge, pop it in... and done. You're ready to inhale. So we've heard people saying that this is difficult to use. I, I challenge them to say, Please show me how this is difficult. So we feel very, very good about the product. We believe it, it's a great product, and we believe that's why it's already reached 4,000 patients in prescribing over the last, say, year and a half. Now, moving on to Insmed, they've made some claims out there. There's been very little clinical data shared. So it's very, it's hard for us to calibrate what their claims are versus what the data says. So we're gonna have to wait and see what they publish at some point, and then determine what impact it might have. And then Sotatercept.
Now, we know the PDUFA date for Sotatercept is in the spring of 2024. And so that's coming. And but one of the things we'll point out, and we talked about this in our earnings calls, is that Sotatercept was commonly prescribed with treprostinil as a background therapy, and it was actually more effective with treprostinil as a background therapy. So we believe it's gonna be positive for treprostinil sales once Sotatercept gets approved. Now, going back to the inhaled product that Liquidia has. Now, there's been claims made about they're able to dose to a higher level than Tyvaso, and that's really not true. We can dose to the same high level.
In fact, in the Tyvaso prescribing information, there's no limit to what a patient can go up to. That's really up to the HCP to decide. So an example I'll give also is that their product is really less efficient in delivering the dose. Their strength of 75 mcg of treprostinil is what they needed to achieve an equivalent PK value to nebulized Tyvaso at 54 mcg. Tyvaso DPI is at 48 mcg, so they're achieving an equivalent PK with much more product. And that's partially why they have to deliver a higher dose, is that their device isn't as efficient. So all these are factors that play into how this will affect Tyvaso DPI as we look at it.
Right. Yeah, I mean, I guess, like, one question, just as a follow-up. From the peers that I've talked to, just on, I'm more interested in learning about Sotatercept, and one of the things that has, you know, come up in conversations is that there is impact from how much prices their product is how peers are looking at it. So if they are trying to go, like, early line therapy and come with, like, a really low price, as opposed to, like, late line therapy with a premium price, that might have implications for Tyvaso, one way or the other. Do you buy that argument, or do you think that it doesn't necessarily change the impact depending on the pricing strategy?
I mean, yeah, I think there could be an impact. We'll have to wait and see. But it's a crowded market now, and everybody's at different levels of pricing. Really, we've been able to maintain our presence in PAH despite all the competition. Treprostinil is a great molecule. It's really the gold standard to treat PAH still today, which is why companies are continuing to develop alternate versions of it. So, you know, we'll have to see how it all plays out.
Good. So just in the two minutes that we have, anything that you can share on the, as you know, heart and kidney transplant facilities, like any timelines or goalposts that you can establish for when we might start to see a lot of progress and tangible?
Yeah. So a quick update on the xeno program. So, made a lot of progress with both heart and kidney, and we've been able to demonstrate functionality of both the heart and the kidney in non-human primate decedent human models, and of course, the two human transplants that were done at the University of Maryland, both last year and this year. Now, as far as preparing for clinical trial, our regulatory team has been working with FDA to outline the requirements needed to file an IND, and that work is in progress. Right now, we expect to be able to file an IND for kidney, probably towards the end of 2024, maybe early 2025.
And the heart will be not so far behind it, and these are both with the 10-gene modification that we've talked about publicly. Now, as we prepare to begin a clinical trial, we've constructed a clinical designated pathogen-free facility, which will house the genetically modified pigs. And construction of that facility is nearly complete. It will be done by the end of the year, and we plan to populate that facility in the first quarter of 2024, in preparation for having organs available in 2025. Now, that facility alone was a $75 million capital investment to build that facility, and it'll be capable of producing approximately 125 organs a year to support the clinical studies of both xeno heart and xeno kidney.
Now, as we look farther into the future, and we've discussed this again in our earnings calls, we've already made preliminary plans to build commercial scale DPS. And these are gonna involve massive capital investment. The first one we will build will be on our North Carolina campus, and we expect that building to cost us between $1.5 billion and $2 billion to build. Now, the output goal of that facility will be approximately 2,000 organs annually. In addition to that, we plan to build two more facilities, really regionally located to support different transplant centers, and these will be a little smaller, possibly 1,000 organ a year facilities. And these are gonna cost, again, in the neighborhood of $1-$1.5 billion.
So we're expecting a lot of capital investment in xeno. We've talked about it being part of the third wave, along with 3D printing and our regenerative medicine programs. So we really do have an eye to the future on this, and it's really going to drive the growth of the company in the future.
Great. Excellent. With that, we can wrap up the session. Thank you so much for your time, Pat, and it was a pleasure having you at our conference.
Thank you.
Yeah.