us this morning, as well as Harry Silvers, Investor Relations. James and Harry, thanks so much for joining us today. How are you both doing?
Good morning. Thank you, Lisa. Really thanks RBC for hosting United Therapeutics this morning. Harry and I are really glad to be here. I'm gonna turn it over to Harry to do an opening statement.
Yeah.
Forward-looking statements before we start, if that's okay.
Perfect.
Thanks for having us, Lisa. Just to remind investors in the crowd and listening in, we may make forward-looking statements. For any risks and uncertainties associated with those statements, please review our latest filings on Form 10-K and Q.
Well, James, Harry, maybe just to kick things off, could you just give us a big-picture overview on what's going on with the company and the base business, and where things stand with expansion, label expansion of TYVASO into IPF?
Lisa. Thank you. It's a great question, I think you'll be hard-pressed, as Martine talked about on the last earnings call, to find a mid-cap biotech company with as many projects and initiatives that are ongoing inside UT. I think as an example, we just proved beyond a shadow of a doubt in two separate clinical trials of clinical efficacy in two different disease states that had better clinical outcomes than really any other clinical trial, and those being the TETON-2 clinical trial using TYVASO, nebulized TYVASO for idiopathic pulmonary fibrosis, as well as the ADVANCE OUTCOMES trial, which is using ralinepag, an oral, once-a-day formulation for PAH.
These indications and opportunities have revenue potential that exceeds what we're expecting as a revenue run rate at the end of 2027, basically to double the revenue run rate with these two indications once they're approved and on the market. Between these two clinical trials and all the other stealth programs that we've talked about, we feel the long-term opportunity from a growth perspective at United Therapeutics is significant.
Thanks for that, James. Well, I do wanna dive into IPF and some of the data that you shared at ATS over the weekend. Maybe a big-picture question for both of you. There's been some regulatory volatility. The commissioner of the FDA has stepped down, and I'm just wondering if there can be any impact to any of your regulatory plans, either for IPF or some of your stealth products like the SMI.
Yeah. Thank you, Lisa. It's a good question. From our perspective, we have interactions and ongoing conversations with FDA, even to the extent as of last Friday, we did a press release that announced the advancement of our UHeart clinical trial for our organ manufacturing products, which is pretty revolutionary. Including that clinical trial for the UHeart, we have three clinical trials in organ manufacturing. Just to bring it back to your question, we've had great dialogue with the FDA. Even with transitions at the top of the organizations, we're really working with divisions within the FDA, cardiopulmonary, et cetera, and our relationships, our conversations, have actually been extremely good, extremely consistent.
The reason why I went back to this manufactured organ UHeart discussion is the FDA, our dialogue with them has been very great. We're advancing projects and programs on our own and in conversations with the FDA, and it's been a very healthy dialogue, so no disruptions on our part.
Great. That's great to hear. James and Harry, you were both at the American Thoracic Society meeting this weekend. United had a bunch of presentations, but maybe you could share some color on how the presentations for ralinepag, the ADVANCE OUTCOMES study that you alluded to earlier, as well as the TETON studies for IPF, how were those received by the medical community?
Yeah. Lisa, I'll let Harry actually was there live and in person, so if you don't mind, I'm gonna defer to Harry on this one.
Yeah. Thanks for the question. I am fresh off the ground from Orlando. You know, first of all, it's great to see, you know, at ATS, the community come together in pursuit of better outcomes for patients. Just a really great energy there overall, and particularly in our two breaking news sessions which were accepted in the clinical trial session on Sunday. The receptivity really, I think, mirrors our own excitement in the large opportunities ahead in both IPF and ralinepag for PAH, when you think about just the magnitude of the results that were presented, providing better options for patients than may currently be available.
Got it. Thanks, Harry. Let's dive into IPF a little bit more. The TETON studies really showed unprecedented results in the IPF patient population, and there were really convincing benefits with TYVASO, not only as a monotherapy but also as add-on to current standard of care, the antifibrotic drugs. Maybe, starting with the regulatory question, kind of a next steps kind of question, what is gating for the sNDA package that you're planning to submit before the end of the summer?
Yeah, it's sort of a regular process putting together the clinical study reports. We also have to do the integrated analysis report because there were two separate trials, TETON-1 and TETON-2, and just, you know, submitting all the regular requirements for the draft package inclusion. We're on track for a filing by the end of the summer.
Harry, should we expect to see priority review?
It's a good question, one that we get often. You know, what we think is that the magnitude of the data, combined with just the still unmet need of this disease state could warrant priority review, and we're hopeful to get that.
I can assure you internally, and the regulatory team are looking at every opportunity they can. One is to get the filing done right. We always have time to get it done right. Two is looking for the opportunity to advance it because of the benefit that you saw in the clinical trials. We really wanna make sure we can get that to patients.
Does the Commissioner's National Priority Review Voucher count as looking at every angle, every opportunity?
Okay. Any insight, but we'll look at every opportunity.
Well, I like to joke that it was called, you know, colloquially the Makary voucher, and well, we all know he's not around anymore. It's kinda nebulous, I think.
Yeah.
Well, fair enough. Maybe let's talk about a potential launch in IPF. Which patients would be the low-hanging fruit here? Should we think of refractory patients who are already on a oral antifibrotic pill, those who maybe cannot tolerate the oral therapies?
Yeah. I would say it's pretty clear from the data, just based on the magnitude of the benefit observed, the consistency across all the subgroups, and the safety and tolerability profile, which is well known, that almost any patient could and should benefit from this therapy.
Do you think doctors are interested in using TYVASO as a first-line monotherapy? I mean, we saw with the combined TETON results that it was statistically significant as a monotherapy. Is that something that, you know, doctors are talking about at ATS maybe?
Yeah, absolutely. You certainly hear that bubble up in the conversations, and we ourselves have said this, the same thing. Kind of again mirroring my first answer, it's very clear from the data when you look across every patient in the study really seems that they could benefit. You know, you think about the first, the existing antifibrotic agents too, like they're so untolerable, and the efficacy really seems to be waning over time for those drugs. I think positioning this, you know, ahead of those could be beneficial, and certainly you'll probably see doctors try that.
Are any doctors interested in trying TYVASO as an add-on to JASCAYD, the most recent IPF antifibrotic that was launched?
Obviously there's no clinical data. The TETON studies did not contemplate nerandomilast. I think there is a very clear scientific reasonableness to try out the combo and suspect doctors would do that.
Got it. That's helpful. Maybe just a last one here on IPF. You announced during the first quarter that, you know, there was gonna be plans to develop not just nebulized TYVASO, but TYVASO DPI for IPF. Given that you have the TETON results in hand with the nebulized formulation, what do you need to do to get the DPI formulation across the line and get it to IPF patients?
Yeah. Again, a question that we're getting a lot. You know, we certainly can appreciate the opportunity in terms of the convenience of the DPI. What I would say is we're still working out the clinical development pathway when you think about branching out into the fibrotic disease with an entirely new compound into that space, an entirely new device into that space. We certainly look forward to sharing more as we finalize those plans.
Got it. Well, I do want to talk and spend a little bit more time talking about the Q1 results as well as some of your forward-looking guidance, like the $4 billion run rate and beyond. Maybe for you, James, we can just dive in here. Q1, the TYVASO franchise, you know, came in a little bit light versus consensus estimates, but it sounded like this was partially due to the awful winter weather that we had and maybe some challenges at one of your specialty pharmacies. Yet you are continuing to guide double-digit top-line growth for 2026. My question is, how do we get there? How do we get the double-digit growth for this year?
Thank you, Lisa. It's a good question. At a top level, we do remain very confident in the long-term growth of TYVASO DPI, and we say that with conviction. We believe that as a device, it is very simple, easy to use from a dosing perspective. It has unlimited dosing. We think the benefit that has already been realized by the thousands of patients and prescribing physicians sets it up for the long-term growth opportunity. It's a space that we know extremely well, and it's a network of prescribing physicians that we feel we're gonna continue to grow in that space.
As you alluded to, there were some anomalies that occurred in the first quarter, that is something that we have addressed internally, and we really look to the long-term opportunity that TYVASO provides to the patient population, including better tolerability, for example, over the long term. There's many attributes and reasons why I believe this is for us to own. And over the long term, we still believe at the end of the day we're gonna be the best prostacyclin prescribe for TYVASO DPI in the market.
Do you think now that the TETON data is widely available now, you have two New England Journal of Medicine publications, you have all these presentations just this weekend at ATS, could we perhaps start to see doctors try to find PH diagnoses in their IPF patients to essentially get them to a true PH-ILD diagnosis and get more patients onto TYVASO?
From an approved product perspective, PAH and PH-ILD are the approved indications. PH-ILD is obviously the growth driver for us and will continue to be until these two new indications, one being nebulized TYVASO and IPF. I think you're right, though. From an awareness perspective, with all the presentations, publications, I think physicians are highly aware of it. How they diagnose and look at their patient populations will be really up to them. We think the awareness and the opportunity to improve the patient outcomes is there for sure.
Got it. I do wanna talk about your competition, your competitor, Liquidia. They, you know, in Q1, they beat estimates, their product, YUTREPIA, arguably now has about 30% of the inhaled treprostinil market, I guess we could debate that number on a revenue basis.
I hearing in terms of feedback from doctors in terms of how their experience compares with YUTREPIA versus how it compares with TYVASO, and where can either win in PH and PH-ILD patients with TYVASO?
Yeah, I think where we win is, to some extent, Lisa, what I just mentioned too. I think this is a long game. I think our device, the delivery mechanisms, the deep into the lung penetration, things we've talked about as benefits with the device itself, in the long term will resonate with physicians and will actually be a benefit, we think, to patients. There is some internal, as you alluded to, you know, logistics, jocking, things going around right now with competition. We do think from a product perspective, we do have a superior product, and we think over the long term that's gonna resonate best with patients and physicians. We're confident in that regard. I think time will tell.
I think the sales force that Michael talked about is there should see some expansion later this summer as we onboard new sales teams for an advance of the IPF launch. They're gonna be specifically focused on PH-ILD, will give us more voice, kind of feet on the street, again, to raise awareness. I think in the long term, what I think will resonate best is really the product profile of TYVASO DPI as a product and benefit for the patients long term.
I do want to touch on the 2027 $4 billion run rate that has been reiterated multiple times now. That means you're going to reach at least one quarter with a $1 billion in revenue that year. What are the key drivers? How do we get there? Is this mostly going to be driven by the IPF launch as well as the ralinepag launch in PAH?
Yeah, thanks. Good question. What we've talked about now for some time is that by the end of 2027, Lisa, we'll be on a quarterly revenue run rate of $1 billion. It will be a $4 billion run rate. When we started talking about this, the basis for that was really gonna be driven off the commercial business, so the existing business, which would be obviously the growth in, for us, TYVASO DPI, and in the indication of PH-ILD. That's really the commercial foundation, the commercial footprint of our current commercial products to get to a $4 billion run rate.
The doubling of revenue to get to the $8 billion run rate that we've talked about would be with the approved indications for ralinepag in PAH and for TYVASO nebulized in IPF. Right now, this $4 billion run rate is off the commercial portfolio, driven primarily off PH-ILD and TYVASO DPI.
Got it. That's really helpful. The $8 billion run rate, does that include also some of your other products like TRESMI or ralinepag DPI?
Okay. It could, but I think primarily it's gonna be off the indications of TYVASO nebulized and IPF, as well as ralinepag and PAH. Certainly if there's any contributions from other products that are in development and in stealth mode, and some not in stealth mode actually anymore because they came out on the last call, there could be revenue contributions. The real focus has been to get to the $4 billion-$8 billion on IPF as well as PAH for ralinepag.
Maybe this is a good segue to talk about some of those new products that have been released out into the open, so TRESMI and ral DPI. On TRESMI first, is everything on track for the FDA filing later this year and potential launch in 2027?
Yeah, to be clear, so you're talking about treprostinil SMI. Yes, our expectation is later this year we'll be filing for the indications where TYVASO is currently approved, so PAH and PH-ILD.
Got it. When or if could TRESMI treprostinil SMI be expanded into IPF?
Yeah, kind of similar to earlier when we talked about TYVASO DPI into IPF. We're still working out the clinical development pathway. It's an entirely different division of the FDA than we typically work with. Cardio Renal Division covers the pulmonary hypertension indications, and the pulmonary division covers the fibrotic diseases. You know, they have less familiarity with treprostinil, with some of the bridging studies that we've done before.
It's possible a bridging study may look different and less expeditious than what we're seeing in PAH and PH-ILD, but we're still working on those plans and excited to share more.
Got it. Ralinepag DPI, this is your once daily inhalable answer to Insmed's TPIP. This was brought out of stealth mode during Q1. There's a lot of excitement about this. When can we get our first look at clinical results of ralinepag DPI?
Nothing to commit to right now on timing for when you might see any data. You know, we are planning to move into phase I later this year in the PAH indication with ralinepag DPI.
Got it. Maybe what are the goals here with ralinepag DPI? Should we just think of this as a convenience play? Is this life cycle management? Is this a hedge just versus the competitors out there? Could this be a best in class inhalable prostacyclin agent?
Well I think we can start where you ended. It could be a best in class for sure. I think one thing you'll find, the data with ralinepag in the ADVANCE OUTCOMES was so compelling, that it does set up the opportunity to go into other indications as we talked about. As an organization, what you find with UT is we actually have the concept what we call multiple shots on goals. Going back to your earlier question, ralinepag DPI, it's not necessarily response to anybody, but it's more our own innovation going forward of how we want to develop our products, to satisfy the multitude of what Michael Benkowitz called on the earnings call, you know, every patient is like a snowflake. They are very different in kind.
We want to make sure we're developing not only therapies, but platforms and delivery devices that best suit and satisfy the needs of the patient ultimately, and their relationships with the prescribing physician. Whether it's ralinepag or whether it's your prior questions around TRESMI, so SMI, it's just really a philosophy and a development program where you're seeing the outcomes of the product development team and the clinical development teams actually accomplishing an enormous amount of work. They're taking us to levels, new heights and new levels at United Therapeutics, that we haven't seen yet. A lot of kudos to them.
I think, Lisa, coming back to your question, we're really going to take the opportunity based upon our product set, things you know about, some things you don't know about that are still in stealth mode, to ultimately provide the best opportunity for treatment for our patients for the long term. Again, it goes to the platforms we talked about in organ manufacturing. You just saw or heard about last Friday, this press release on the advancement in organ manufacturing for the UHeart. Again, these are opportunities for us to think about ways to satisfy what we call the corridors of indifference overall, where we have a lot of opportunity to run very little competition, and we can help and support and serve the patients the best we can.
Maybe on that note on the xenotransplant program, you have the xenotransplant program going on, the EXPAND study, in kidney and of course, the UHeart program, which was just launched into the clinic last Friday, which you announced. I guess, when should we expect to hear any updates on these programs going forward?
Yeah. You know, I think going forward, we'll doubt what the disclosure strategy looks like. The way the studies are designed, at least the ones that are currently enrolling right now between the 10-gene kidney and the one-gene kidney with the thymus attached, it's cohort-based with the first cohort of six patients, after which time you meet with the FDA to get a green light on the second cohort, which becomes registrational. You know, there may be a natural point in time after the first cohort where we could have a data package to share, but nothing to commit to at this time in terms of when, where, or in what format you might see data.
Maybe a bigger picture question for the xenotransplant program. Is the goal, for instance, in kidney, is the goal to delay dialysis? Is the goal to bridge patients to potentially receiving a transplant with a human kidney? Or is the goal to, you know, get a new kidney as needed because these are off the shelf and you could possibly do that?
We think in the long term it would be a replacement, for example, to an allograft. We don't want to be in a situation for somebody to live, to only be have that opportunity if somebody passed away. This is a chance to provide an unlimited supply of organs to patients that could have similar duration in terms of length as allografts that you currently see or even longer. This is an opportunity, we think, to be able to provide and satisfy this huge demand. As we sit here today, there's 500,000 patients on dialysis who are in need of a kidney.
We think that we could give them, ultimately, if this is successful, a kidney that would last as long as an allograft or longer, just as comparison, and maybe not need a new one. Should they need one, we would be ready to provide them one as well, should the program be successful.
Well, James, on that note, we are out of time. We'll end things there. James, Harry, pleasure to have you both this morning. Thanks so much for joining us.
Lisa, thanks for having us.
Thank you.