United Therapeutics - Q2 2023

Transcript

Operator (participant)

Good morning, and welcome to the United Therapeutics Corporation second quarter 2023 earnings webcast. My name is Danielle, 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 one on your telephone keypad. If you would like to withdraw your question, please press star, then two. Please note this call is being recorded. I will now turn the webcast over to Dewey Steadman, Head of Investor Relations at United Therapeutics.

Dewey Steadman (Head of Investor Relations)

Thanks, Danielle, and Good morning. It's my pleasure to welcome you to the United Therapeutics Corporation second quarter 2023 earnings webcast. Accompanying me on today's webcast are Dr. Martine Rothblatt, our Chairperson and Chief Executive Officer; Michael Benkowitz, our President and Chief Operating Officer; James Edgemond, our Chief Financial Officer and Treasurer; Pat Poisson, our Executive Vice President of Technical Operations; and Dr. Leigh Peterson, our Senior Vice President of Product Development. Please note that 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, and we assume no obligation to update these forward-looking statements. Today's remarks also 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. Remember, full prescribing information for our products are available on our website. Note that Pat Poisson and I will be participating in one-on-one meetings at the 2023 Wedbush PacGrow Healthcare Conference on August 8th. Michael Benkowitz, James Edgemond, and I will participate in a fireside chat and one-on-one meetings at the Morgan Stanley 21st Annual Global Healthcare Conference on September 11th. In addition, we will present data at the European Society of Cardiology in Amsterdam in August, the European Respiratory Society in Milan in September, and at the CHEST Annual Meeting in Hawaii in October.

I will turn the webcast over to Dr. Rothblatt for an overview of our second quarter 2023 financial results and the business activities of United Therapeutics. Martine?

Martine Rothblatt (Chairperson and CEO)

Thank you, Dewey. I'm thrilled that United Therapeutics continues to report double-digit revenue growth and our highest quarterly revenue ever. We expect this growth trajectory to continue with our current business as we expect to reach a $4 billion annual revenue run rate by mid-decade. Beyond that, we expect continued waves of growth, with an additional doubling of our revenue from the potential launch of Tyvaso in pulmonary fibrosis and of ralinepag in pulmonary arterial hypertension, then yet another doubling of our revenues, with the potential for an unlimited supply of tolerable transplantable organs in the next decade. Let me now dive a little bit deeper into some of these, you know, absolutely fantastic results that we are pleased to report this quarter. As mentioned, the total revenues are at $596 million for the three months.

It's interesting to compare that with the matching three months of last year, which were just about $467 million. That's a percentage growth rate of 28% and very much in line with the type of growth rate that we have previously indicated, we expect to achieve in order to achieve that $4 billion revenue run rate by mid decade. Another deeper level to look at is the company's net income. For the past quarter, we reported over $250 million in net income. Again, it's instructive to compare that with the quarter, matching quarter in 2022, when we reported $116 million in net income, a percentage change of 123%.

Very comparable numbers can be obtained if you divide the net income into the outstanding shares. In fact, we're pretty proud that as compared to peers, we have a relatively low number of shares outstanding, which helps drive those fantastic results. Now, let's dive even deeper into some of the results on the products. Tyvaso, $319 million, up 59% from last year. Remodulin, $127 million, down about $5 million from the matching quarter last year. Orenitram, $95 million, up 20% from the matching quarter last year. Unituxin, $44 million, essentially flat from the matching quarter last year.

We don't really talk that much about Unituxin, but I probably should stop and for people who are perhaps newer to United Therapeutics, remind everyone that this is a treatment for neuroblastoma, pediatric cancer with a very high rate of mortality. For the based on the several years that Unituxin has been used by doctors to treat that cancer, approximately 50% of the kids treated with Unituxin, as well as the other concomitant therapies used, their cancer is wiped out. It does not return. Even five years later, when they're checked, the cancer has not returned in about half of the patients.

I, I find that, you know, truly remarkable and just a, a miracle of biotechnology, and one of the many blessings to be here at United Therapeutics, that so many kids can live a cancer-free life after getting that devastating diagnosis in their tender years. In any event, because that drug is so well-used by the pediatric oncologists, we're now looking at on an annualized basis, you know, it's getting close to $200 million a year. In addition to those top-line revenues and profit figures, let's dive a little bit into the spending section.

Here we break out our, our spending in large categories, in terms of, external research and development, internal research and development, and then the general administrative and sales and marketing categories, with a few miscellaneous rows, put in there according to GAAP standards. The external research and development is what we spend on, on other companies assisting us with our research and development. The lion's share of that money goes to conducting our worldwide clinical trials. We've got quite a few clinical trials going on right now, and most of them are in the phase III stage of development, which is, you know, the largest and the most costly phase of development. We have the 2 TETON 1 and TETON 2 phase III trials for idiopathic pulmonary fibrosis.

We have this new TETON 3, or also called PPF type of pulmonary fibrosis, which is another phase III trial just starting up this year. We have the ongoing worldwide ralinepag clinical trials, covering, you know, countries, you know, in almost every continent. That is a more expensive clinical trial because that clinical trial is aiming for an endpoint to show that we reduce death and morbidity in patients with pulmonary hypertension. We have to both enroll more patients and keep the study going longer until we get a statistically significant difference in the death rates. We look at that and hope to achieve our statistical significance with respect to the treated or active group. We also still are ongoing with the gene therapy trial.

All of these trials combined, they, they end up costing us more than $100 million a year just in spending outside of the company, and that's not even talking about the, the level of spending inside of the company. Now, inside of the company, we've got our, our great team of clinical drug developers, ultimately led by Dr. Peterson, who joins me on the call today, and she has just been doing an amazing, amazing job of running all of these phase III trials simultaneously. It really, it, it takes a humongous amount of effort to get drug labeled, translated, shipped to these countries all over the world, constantly be monitoring those centers, sending people there every month to make sure that the protocol is being complied with.

I cannot begin to tell you how long the checklist is to conduct these clinical trials. It's, it's not surprising that, you know, there is another more than $100 million a year spent on internal research and development. Under the internal research and development category, we also cover the development activities for the organ manufacturing efforts that I described in at the beginning of the call. There we've got the lead program, our xenotransplantation efforts, and they're in accordance with the FDA guidance, which we received in our INTERACT meetings with the FDA, both for the xeno kidney and for the xeno heart. We are proceeding with the pivotal preclinical studies necessary to enable an opening of an IND for xeno kidney and xeno heart.

We are doing our best to hopefully be able to open that IND as soon as possible. It's not really possible to predict exactly when the FDA would feel that it was the appropriate time to do that. I would say that the timeframe for that FDA decision, kind of, you know, reasonable case is a 2024-2025 timeframe. More pessimistic case could be a 2025-2026 timeframe. Any way you look at it, it is, you know, literally around the corner in drug development speak. That's an additional area of significant spend. We also are continuing to spend heavily on our laboratory-based lung manufacturing activities, both with allogeneic as well as with autologous cellularization.

That, too, is a really a trailblazing effort where people, many of them, our own patients who have been treated with our medicines for pulmonary hypertension. In the event that their disease progresses, which is usually the case with pulmonary hypertension, and for that matter, pulmonary fibrosis as well, and of course, many other lung diseases, you progress to the point of needing a lung transplant. We are doing our best to be able to have laboratory manufactured lungs to satisfy those patients' needs for lung transplant. In the meantime, we have a really remarkable program, which we call lung bioengineering.

In this program, we, we take lungs from Organ Procurement Organizations who, for various reasons, the transplant surgeons feel they are not quite ready or certain that they want to use that donor lung for to put into a very, very sick person who needs that lung. They ask the Organ Procurement Organizations to fly those lungs to one of our two lung bioengineering centers. One is in Silver Spring, Maryland, across the street from our headquarters, and the other is in Jacksonville, Florida, on the campus of the Mayo Clinic. There are highly skilled, highly trained technicians.

They work on the lung like a person would, like a doctor would work on a, on a patient, or a surgeon would work on a patient, and they do everything that they can to render that lung suitable for transplantation. Again, quite, to me, as, as, as a person who's actually never done the procedure, I'm, like, blown away that half of the time they succeed. A lung that was not going to be used to save a person's life is, in fact, able to be used to save a person's life. To date, we have saved over 300 people's lives with these, lung bioengineering products.

I'll also mention, just kind of coincidentally, that when we are not able to use the lung to save a person's life, we are oftentimes able to use the cells from the lung to assist in our efforts to manufacture allogeneically cellularized lungs in our laboratories. It's kind of everything all fits together here at United Therapeutics. I know I've talked on for quite a while here, but there is just so many exciting things going on at United Therapeutics. We have been able to build up a substantial cash balance, and we are targeting that for three main areas of deployment. First and foremost is to invest in all of the internal projects that we have going here at United Therapeutics, and I've mentioned several of them in my remarks today.

You may recall just last quarter, we talked about $500 million being allocated to the production of a dedicated Tyvaso DPI production facility on our campus in Research Triangle Park, North Carolina. That is in recognition of the, you know, very excellent take-up that the Tyvaso DPI product has seen among physicians, patients and their families, all supporting the patients in that regard. Then another area of capital deployment would be to build the GMP equivalent production facilities for the xeno kidneys and xeno hearts that I mentioned previously. Of course, the FDA wants to see, and we would also want to see that those xeno kidneys and xeno hearts are manufactured in a totally clinically appropriate fashion, which requires the animal equivalent of a GMP facility.

The, the technical name for it is a designated pathogen-free facility, so capital is also targeted for that. In addition, we have a very robust business development group, led by Dr. Betsy Eads of our company, and she is frequently bringing to us often very compelling candidates for potential either investment or outright acquisition, and we need to retain adequate capital for those opportunities. You may recall that, I think, you know, probably the, the next biggest impact drug that we could have in pulmonary hypertension, ralinepag, was acquired through our business development efforts for $1 billion. These type of opportunities are regularly being reviewed by Dr. Eads.

Then, then third is to repurchase shares to the extent that there is excess capital that can't be deployed for internal business development or external business development. Of course, the next up would be to engage in share repurchases, and we have repurchased lots of shares over time. In fact, I mentioned earlier that our outstanding share count is relatively modest compared to peers, and that is because, in no small part, our previous share repurchases. With those introductory remarks, I'd now like to turn the phone over to Michael Benkowitz, our President and Chief Operating Officer. Mike?

Michael Benkowitz (President and COO)

Thanks, Martine. Good morning, everyone. As Martine said, we had a phenomenal second quarter from a revenue standpoint, setting revenue records for Tyvaso, Orenitram, and total treprostinil. I wanna begin by publicly thanking and congratulating all of our commercial medical affairs teams at United Therapeutics for their hard work and achievements during the quarter. As usual, I'll provide some color on what we're seeing with respect to Tyvaso, Orenitram, and Remodulin. I'll start with Tyvaso, where I wanna highlight several things. I should also mention that for purposes of these comments, Tyvaso refers to the combined nebulizer and DPI, unless I otherwise note.

First, as I just mentioned, we posted the highest quarterly revenues ever for Tyvaso, which reflects increasing physician and patient demand in both the PAH and PH-ILD indications, as well as the Tyvaso DPI inventory build of about $30 million in the quarter at the specialty pharmacies. Our underlying demand metrics, that is, referrals, which is what we call prescriptions, new patient starts, and net patient adds, remain very strong and roughly in line with the last few quarters. New patient starts are trending around a 70/30 split between DPI and the nebulizer, respectively. The transitioning of long-term existing nebulized Tyvaso patients to Tyvaso DPI has largely played out at this point, at least until the Part D redesign provisions of the Inflation Reduction Act begin to go into effect over the next two years.

In fact, nebulized Tyvaso referrals and starts have trended upward over the last few months. We do expect that there will be some basal level of transitioning between the nebulizer and DPI going forward, as physicians optimize to which delivery device is best suited to each of their patients. We also continue to make great progress growing the Tyvaso prescriber base and prescribing depth within that base. On the Tyvaso DPI supply side, our partner, MannKind, completed their production expansion and process improvement efforts during the quarter, which we expect will increase production capacity by about 250% going forward. We started to benefit from these enhancements at the end of June, when, as I mentioned, the specialty pharmacies were able to build about $30 million of DPI inventory.

Specialty pharmacy inventory levels on the last day of the quarter actually reached their contractual range based on historical demand. However, this could fluctuate through the remainder of the year as Tyvaso DPI demand grows and until MannKind has a few more months of production with the additional capacity. We anticipate that specialty pharmacies may be able to get into their regular ordering patterns for Tyvaso DPI sometime either later this year or in the first half of 2024. As a reminder, MannKind is also undertaking work to further expand production capacity, even beyond these most recent improvements, which we would expect will come online in 2024. I should also note that the nebulizer destocking that we highlighted in the fourth quarter of last year and first quarter of this year, did in fact conclude in the first quarter.

Second quarter nebulizer orders were in line with specialty pharmacy contractual inventory levels and patient demand. To wrap up the Tyvaso story, we're extremely pleased with the progress we've made and the opportunity that lies ahead of us. Our focus and efforts in the second half of this year and into 2024 fall into four main areas. First is increasing production and supply of Tyvaso DPI in partnership with MannKind. Second is increasing physician screening for PH ILD and their ILD patient population. Third is growing the prescribing breadth and driving depth to three-plus patients, as I mentioned on prior calls. Fourth is continuing to increase patient retention on Tyvaso. While we've made very good progress on each of these items thus far, there's still more we can do.

To this end, we recently realigned product promotional responsibilities within our existing commercial headcount and are in the middle of a headcount expansion, including in sales, to drive these efforts. Turning to Remodulin, this business continues to be incredibly resilient, even though it has faced generic competition for almost four years now. Continuing a trend that started last quarter, we saw a near record number of referrals in the second quarter, and active Remodulin patients remain at pre-generic levels. Remunity continues to gain traction in the market, as it is the only subcutaneous pump widely available for new Remodulin patient starts. Finally, Orenitram had another record quarter with the highest revenue in patients on therapy since its launch. Our 90-day tri-titration kit, launched during the first quarter, has continued to receive positive patient and physician feedback.

We're also very excited that data from the EXPEDITE trial, which is our rapid Remodulin titration and transition to Orenitram study, has now been published in two medical journals. We look forward to disseminating this important information to clinicians in appropriate forums over the balance of this year and into next.

Pat Poisson (EVP of Technical Operations)

To wrap up, we're very pleased with the overall treprostinil business, led by the incredible, incredible demand for Tyvaso DPI, and we believe we're on our way to hitting our goal of a $4 billion annual revenue run rate by the middle of the decade. With that, I'll turn the call back over to you, Martine.

Martine Rothblatt (Chairperson and CEO)

Mike, that was an amazing, awesome wrap-up. Thank you so much. How you stay on top of so many details blows my mind. Perfect. Wow! We have the best and the president. Thank you, Mike. Okay, operator, please open up the lines for any questions and, like, I'll forward them amongst Mike, Pat, and Dr. Peterson.

Operator (participant)

Thank you. We will now begin the question and answer session. To ask a question, you may press Star, then one on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press Star, then two. The first question comes from Ashwani Verma of UBS. Please go ahead.

Ashwani Verma (Executive Director)

Hi. Thanks. Good morning, and congrats for a very strong quarter here. I have two questions. One, just on Tyvaso in IPF. Wanted to ask, what's your level of conviction in clinical success here? The prior INCREASE study showed benefit in the PH IPF subset, but in the TETON studies, you're studying IPF all comers. Second one, can you provide some color on the patient adds? Like, how much of the new patient adds is coming from PH versus PH-ILD, and do you expect the patient adds per quarter to start to ramp up faster in the coming quarters and years? Thanks.

Martine Rothblatt (Chairperson and CEO)

Ash, thank you for your question, and thanks for the congratulations. We have so many callers in the queue. I'm just gonna have to limit it to 1 question per caller. We'll take your first question about pulmonary fibrosis. Dr. Peterson, could you kindly respond to Ash's question?

Leigh Peterson (EVP of Product Development and Xenotransplantation)

Yes, sure. Thanks for the question. As you mentioned, that we had data from INCREASE in PH IPF, a subpopulation of INCREASE that exhibited improvements in FVC, which is a marker that indicates potentially an anti-fibrotic activity of Tyvaso. This, in addition to many, many publications on also a mechanism for Tyvaso, which is anti-fibrotic, gives us confidence that it will also work in the population of TETON 1 and TETON 2, which are IPF, idiopathic pulmonary fibrosis, as well as our new study in PPF, which is progressive pulmonary fibrosis.

Martine Rothblatt (Chairperson and CEO)

That's excellent. Thank you so much, Dr. Peterson. Operator, could you please take the next caller?

Operator (participant)

The next question comes from Eun Yang, from Jefferies. Please go ahead.

Eun Yang (Managing Director and Senior Equity Analyst)

Thank you. Congrats on the great quarter. That's amazing numbers on Tyvaso. The question on the DPI inventory build about $30 million in second quarter, would that be the inventory levels that you would expect going forward, or do you think it would increase, or could there be some drawdown in third quarter? Thank you.

Martine Rothblatt (Chairperson and CEO)

Great question, so nice to hear your voice this morning, Eun. Thank you for the congratulations. The questions with regard to inventory, we normally ask our Chief Financial Officer, James Edgemond, to handle, because he's totally on top of the flow of everything of value in and out of the company. James, could you please answer Eun's question?

James Edgemond (CFO and Treasurer)

Yes. Thanks, Martine. Good morning, Eun, and thanks for the congrats on the quarter. Two, two parts to the response. Michael talked about the $30 million addition to DPI inventory during the quarter, which was specific to DPI inventory build, and Michael addressed nebulizers inventory as well, which is pretty much normalized. With respect to the demand for DPI for the balance of the year, as Michael talked about, this could really fluctuate going forward through the remainder of the year as we think about patient demand, as well as the manufacturing at mind, at MannKind, as we work through some of the improvements that we've highlighted. Going forward, there certainly could be a fluctuation in DPI inventory, but I would want to reiterate what Michael said.

Across the portfolio of products, as we completed the quarter, we were in contractual requirements with all the products. It is important to highlight the DPI fluctuation going forward based upon demand as well as manufacturing at MannKind. Thanks for the question, and Martine, back to you.

Martine Rothblatt (Chairperson and CEO)

James, just excellent answer as always. Thank you, and Eun, thanks for asking the question. Operator, can you please pull up the next person from the queue?

Operator (participant)

The next question comes from Hartaj Singh, from Oppenheimer. Please go ahead.

Hartaj Singh (Managing Director and Stock Analyst)

Great, thank you for the question and the really nice quarter. Really tough comp last year, last year at this quarter, so it's really well done. Just a question on ralinepag. You know, assuming thephase IIIs are successful, Martine and team, how do you see the product sort of, you know, where do you see it being used in the treatment paradigm? Is it a straight replacement for Orenitram? Will it take some of the Selexipag patients? There could be some generics there by then. Any thoughts there? Thank you.

Martine Rothblatt (Chairperson and CEO)

Yeah, that's a, that's a great question. I'm really happy to have it. You know, I think, Hartaj, you've been able to ask a question that kind of transcends 2 different areas. Unusually, I'm gonna ask 2 separate team members to respond to your question with regard to their different levels of involvement in the frontline treatment for pulmonary hypertension clinical situation and market. First of all, Mike, if you could answer Hartaj in terms of where you see placing ralinepag once approved in the in the basically the presentation of treatment options that would be presented to physicians by especially by our sales force.

Then, perhaps, Lee, if after Mike talks, you can provide, you know, some insight that you're able to share from our clinical trials in terms of how you see what the protocol calls for in our clinical trials, and, and that might also help to shed some light on Hartaj's question in terms of where it's being used in the clinical trial. Outcomes in particular.

Michael Benkowitz (President and COO)

Yep.

Martine Rothblatt (Chairperson and CEO)

Mike, you first.

Michael Benkowitz (President and COO)

Sure. Again, you know, all of this is obviously contingent on how the study reads out the data and kind of what we see through the trial, Hartaj. I think generally, generally speaking, I think we expect that, you know, you'll still start with a PDE5 and an ERA. Then at that point, as you know, once the disease, the patient's disease continues to progress, the doctor has an option as to what to add. That's where I think, you know, we're expecting that ralinepag's sweet spot is gonna be right after the PDE5 and ERA.

Now, you know, for, for various reasons, depending on where the, where the, you know, where the patient is in their disease journey, it could be maybe they need something stronger, so they go to Orenitram, or maybe they want the, the convenience of DPI, so they start there, and then they kind of transition back and forth. I really kind of look at it as being, you know, sort of in that, in that, in that sort of area of after PDE5 and ERA and patient's disease has started to, to progress further.

Martine Rothblatt (Chairperson and CEO)

Yeah, Mike, that makes such perfect sense because, you know, it would really be, to my understanding, you know, the only once-a-day prostacyclin category. It's not exactly a prostacyclin analog, but it works on that pathway. The only once-a-day treatment, which will just be huge for the patients, because if you, if you miss even, you know, a few doses, this disease is insidious, and it could just start reclaiming territory in your lungs. Compliance is king, and once-a-day is the emperor type of delivery for compliance. Leigh, what kind of insights do you have on Hartaj's question from the conduct of the outcome study?

Leigh Peterson (EVP of Product Development and Xenotransplantation)

Yeah. Really with Michael just said, with regard to Selexipag, I mean, of course, we're shooting for a better clinical effect, but also that the fact that Michael just said, it's ralinepag is once daily dosing versus twice. I mean, that's most patients feel that that's an advantage. Scientifically, with about your question regarding Orenitram, now, you might remember that Orenitram or treprostinil, actually, binds and interacts with multiple prostacyclin receptors, versus Selexipag and ralinepag, who are IP specific activators of the IP-only receptor. It's thought, at least from several non-clinical studies, that these different receptors have different activities.

This, this could very well translate to the clinic, where, where certain patients do better when they have binding and activation of multiple prostacyclin receptors. Some patients might, might do better with regard to both tolerability and efficacy if they, if they simply have binding and activation of the IP receptor. So I hope that answers your question as to where, where we see things. It's not a complete overlap with regard to the mechanisms of action, for sure.

Martine Rothblatt (Chairperson and CEO)

Brilliant answer. Wow! That's why I'm so glad we have a scientist on the call. Hartaj, I'm so glad you asked the question, because look at all the information that got, you know, shared through your question. Thank you. Operator, next question.

Operator (participant)

The next question comes from Terence Flynn of Morgan Stanley. Please go ahead.

Terence Flynn (Managing Director and Senior US Pharma and Biotech Analyst)

Great. Thanks so much for taking the question. Congrats on the quarter. A two-part question for me. Just wondering if you can comment at all on Tyvaso patient start trends in July versus June, as well as, breadth of prescriber base. Mike, I know you, you touched on that, but any more color there would be helpful. Thank you.

Martine Rothblatt (Chairperson and CEO)

Okay. Thank you, Terence. Mike, you got it.

Michael Benkowitz (President and COO)

I think on the, on, on, on the referral start trends in July versus June, I mean, we're continuing. You know, it's been pretty consistent, I think, over the first half of the year, and that's continuing in, in, into July. I think the, the, the rate of referrals and starts is consistent with, with what we've seen in the first half of the year. I would, I would say on the prescriber growth, I think the rate of growth has been, you know, I think what I've, what I've said is that the last call is that we've, you know, roughly doubled the number of prescribers since we've launched. Month to month, quarter to quarter, that doesn't necessarily change linearly. It's just, it's, it's, it's a little choppy.

You know, that's, it, it's INCREASE marginally above the, the kind of the doubling in the last quarter. We have seen, however, continue, you know, to maybe stronger growth or higher growth in the last quarter in terms of the, the depth of three-plus prescribers. Which is good. I mean, you know, as I said on prior calls, we use the analogy that if we get, if we get the prescribers to three-plus, to three-plus patients, you sort of kind of get the flywheel spinning, and then the other 3 goes to 10 pretty quickly thereafter. We are making really good progress, you know, on that aspect of prescribing depth, and, and as I said, continuing to add top-line prescribers as well.

Martine Rothblatt (Chairperson and CEO)

Thanks so much, Mike. Yeah, that's a great metaphor with the flywheel. You could just see how our success compounds, once doctors start using our medicine. Operator, we have time for just 2 last calls.

Operator (participant)

The next question comes from Joseph Thome of TD Cowen. Please go ahead.

Joseph Thome (Managing Director and Senior Research Analyst)

Hi there. Good morning. Congrats on the quarter, and thank you for taking my question. Maybe just as we think about penetration into the PH-ILD market, where do you think you stand now? Now that the therapy's been on the market for, you know, a couple of years in the indication, have your expectations for the size of this market changed at all? Thank you.

Martine Rothblatt (Chairperson and CEO)

Okay, thank you very much, Joe. Mike, I think you're the best person to answer that.

Michael Benkowitz (President and COO)

Sure. I, you know, I think on, on, on penetration of the market, I think we're in the low single digits. I say think because I still, you know, and this is, I think, a question that, that was asked earlier that we just didn't have time to ask, around the kind of the mix of the PAH and the PH-ILD. I mean, the data coming in on the referrals is still not, not target. It's still a little dirty, so it's not still 100% clean in terms of what's Group 1 or what's, what's Group 3. I think based on kind of what we're seeing, it's, you know, I think it, I think it's fair to say that we're kind of in that low, low single digits of the PH-ILD market.

In terms of the size of the market, nothing's really changed in terms of our understanding of what that is. You know, we kind of started out saying it's at least 30,000. We still, we still think that that's accurate. You can talk to some KOLs who think it's significantly higher than that, and that may be, but, you know, like, like we've said all along, with the 30,000, I mean, that's still a really good size market for us, and so we're really focused on continuing to penetrate in that market. You get, as I said in my opening remarks, really, you know, kind of ramp up the screening of IL, of ILD patients to look for pulmonary hypertension.

Martine Rothblatt (Chairperson and CEO)

Super. Thank you, Mike, so much. Operator, the last question. We just have time for one more. I'm sorry.

Operator (participant)

The the last question comes from Andreas Argyrides from Wedbush. Please go ahead.

Andreas Argyrides (VP and Senior Analyst)

Yeah, thanks, sir. Good morning. Thanks for taking my questions. Honored to be the last one here. Great quarter, another congrats there as well. Lots of, I know lots of good questions from my colleagues on Tyvaso and the market evolving in PAH. Going back to the prepared remarks and the potential use of cash, how are you thinking about outside investment opportunities? Is it just going to be in PH, or maybe perhaps broadening the company's core focus? Thanks.

Martine Rothblatt (Chairperson and CEO)

Yeah, Andreas, deep and interesting question, and I think that we are most interested right now in the pulmonary fibrosis segment in terms of outside investment. It's not to say that we don't have continued interest in the PH segment, but the PH segment is, by I think almost anybody's estimation, a pretty crowded marketplace at this point in time. By reflection, when we started the company, there was no oral treatment approved for PH as well. There was no inhaled treatment approved for PH. In fact, all that was really available was parenteral Flolan.

If you compare that situation with the situation today, I honestly have lost track of how many different drugs and, and, and versions of drugs and, you know, generic versions of drugs there are, but it's, it's certainly over a dozen. PH is a very crowded marketplace. Despite that crowding, there seems to be continued synergy amongst certain drugs in that in that crowded field. For example, the PDE5 inhibitor, Adcirca, which can be taken once daily, is something which is often used in combination with several of the other drugs. Less often, but still, you know, frequently an ERA, such as ambrisentan, can be used in combination with the other drugs.

Increasingly now, our own Orenitram is used in combination with those other two kind of, you know, I don't want to say weaker, but, I'll say, you know, non-treprostinil strength drugs. This kind of combination phenomena means that even though the market is very crowded, there always is still great opportunity for a new drug in terms of being used as combination therapy. That certainly, as Michael Benkowitz mentioned in his discussion of ralinepag, that's our expectation in ralinepag, that it'll be used in combination. Thanks for the congrats, but one thing that maybe didn't get enough highlighting on the call, although Dr. Peterson did talk a bit about it, was the tremendous upswing in growth in Orenitram.

That's no, that's no like coincidence or just something coming out of the blue. That's because increasingly, first of all, Orenitram is being used in combination with the PDE5 and ERAs. It's a convenient pill. Then secondly, we have another study going on to develop confirmatory data. It's called the ARTISAN study, and this study shows that, building on our previous, smaller studies, that you could rapidly switch a patient from a parenteral drug, like parenteral prostacyclins, which are personal to Orenitram, a pill. If you do that, you're able to kind of jump over this valley when you have the side effects of Orenitram without the efficacy.

You're able to jump over that valley and go directly to the efficacy, and you're already kind of inured to the side effects, or they've been mitigated by the time you spent on the parenteral drug. Again, this is all to say that while PH is a crowded area, I think that there is strong room for United Therapeutics to continue to grow. There hasn't been much discussion on this call about Sotatercept, but just to say, some of the best data that has been published so far on Sotatercept is in combination with the treprostinil product. I think combination therapies are the way to go.

Now, kind of exact opposite situation is in pulmonary fibrosis, where you have a comparable size patient population, yet instead of there being a dozen plus approved drugs for it, there are really only 2. It's a very, very different situation. Neither of those 2 are reported to be disease-modifying in any way. They simply have been shown to slow the rate of progression of the disease, which is good, but not as good as being disease-modifying. I'm very hopeful that we will have something that indicates a disease-modifying capability come out of our TETON studies. I'm very hopeful that we can do as much in pulmonary fibrosis as we, as a company, have done in pulmonary hypertension.

I mentioned, when I started to answer your question, Andreas, at the beginning of the company, there were very few prescribers because all the patients died. There was very little hope. United Therapeutics has enabled a kind of a reinvention of the pulmonary hypertension space, that now there's over a dozen drugs and patients, instead of dying from pulmonary hypertension, they live with pulmonary hypertension. There are patients living, literally decades, which is amazing and wonderful. We would like to be able to do the same thing in pulmonary fibrosis that we've done and are doing in pulmonary hypertension. Some of that will be done with internal R&D, such as the great efforts being led by Dr. Peterson, the TETON 1, TETON 2, TETON 3.

We are also keenly interested in deploying our capital for business development activities that could build out and expand our portfolio in pulmonary fibrosis. That's just one example of a disease area outside of pulmonary hypertension that we plan to tackle. Andreas, thank you for your question. Operator, feel free to roll into the wrap-up script.

Operator (participant)

This concludes our question and answer session. I would like to turn it back over to Martine for closing remarks. 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 Presentations section of the United Therapeutics Investor Relations website at ir.unither.com.