United Therapeutics Corporation

Good morning and welcome to the United Therapeutics Corporation fourth quarter and full year 2021 earnings webcast. My name is Emma 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'd like to ask a question during that time, simply press star then the number one on your telephone keypad. If you'd like to withdraw your question, simply press the star and the number one again. I will now turn the webcast over to Dewey Studman, Head of Investor Relations at United Therapeutics.

Good morning, and thank you, Emma. It's my pleasure to welcome you to United Therapeutics Corporation fourth quarter and full year 2021 earnings webcast. Accompanying me on today's call are Dr. Martine Rothblatt, our Chairperson and Chief Executive Officer, Michael Bickowitz, our President and Chief Operating Officer, James Edgeman, our Chief Financial Officer and Treasurer, Pat Poisson, our Executive Vice President of Technical Operations, and Dr. Lee Peterson, Senior Vice President of Product Development. 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 FCC filings, including Forms 10-K and 10-Q, contain additional information on these risks and uncertainties. We assume no obligation to update these forward-looking statements. Today's remarks may also include financial measures that were not prepared in accordance with U.S. generally accepted accounting principles. Reconciliations of these non-GAAP financial measures to the most directly comparable GAAP financial measures can be found in our earnings release available on our website at ir.unithair.com. Today's remarks 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. Full prescribing information for these products are available on our website. Now I'll turn the call over to Dr. Rothblatt for an overview of the fourth quarter and full year 2021 financial results and business activities of United Therapeutics. Dr. Rothblatt?

Good morning, and thank you, Dewey, for that great introduction. We are very excited about this 2021 annual results call. It's 2021, I think beyond a doubt, has been the most exciting year in our company's history. There are a couple of big picture observations here that I'd like to start with, and then I'll go into some more details. From the big picture standpoint, first of all, we grew both patient count and revenues by double digit percentages in 2021. as we had forecast we would do at the start of the year. Generics have not impacted our terprocinal growth trajectory because patients, physicians, payers, they all recognize our outstanding commitment and track record for customer service and supply chain reliability. Our continued double-digit percentage patient growth is how we get to our announced goal of 25,000 patients by 2025, And we remain right on target to make that goal. In fact, we expect double-digit patient growth again this year in 2022. The second real big-picture item is that our organ manufacturing products made a dramatic and highly successful debut with one 10-gene U-heart, two 10-gene U-kidneys, and two U-thymokidneys transplanted. Of course, the focus of everybody is on our living UHeart recipient, Mr. David Bennett, Sr. So I'm very pleased to report that he is doing well at almost two months post-transplant. Specifically, his cardiovascular function at seven weeks is excellent, and there's no sign of rejection even after a 30-day post-operative biopsy. Although he has a lot of non-heart serious health challenges, he said last night, thank you for this chance to live. And my response to Mr. Bennett was, thank you, Mr. Bennett, for giving us this chance to let countless thousands of others also live. I believe our clear-cut successes in 2021 with Xenoproducts Coupled with our core competencies in this area, our gal safe meat, for example, was approved by the FDA in December 2020, and our core competencies in GMP manufacturing and product development all show that our organ manufacturing pipeline is now more credible than ever and of truly momentous potential. Now, beyond these big picture headlines, there has been a great deal of progress in advancing our pharmaceutical pipeline as well. Some highlights are, first, our once-daily treatment for PAH, Relenopeg, is progressing nicely toward wrapping up its Phase III enrollment. Second, our Phase III PERFECT trial, which is testing a first-ever treatment for COPD-related pulmonary hypertension, is steadily racking up more patient randomizations month by month toward completion of its Phase III trial. Our revolutionary disease-modifying effort of idiopathic pulmonary fibrosis, or IPF, which we call the TETON trial, is doing so well in its U.S. Phase III enrollment that we opened up a TETON II Phase III trial outside the U.S. so that we could hopefully offer this product worldwide. Our super convenient Tyveso DPI product remains well positioned for its summer 2022 launch. The FDA did just delay its approval decision from this month to May, but that three-month detour is not important compared to the product's blockbuster revenue potential and patent life well into the 2030s. Three months delay to start on a billion-dollar revenue trajectory is no big deal. Mike will now brief you on our commercial progress, but in summary, for 2021, I can say we hit our patient growth and revenue growth targets. We validated three new xeno organ product candidates, and in so doing, we've launched a whole new category of biotechnology. We have seven phase three trials underway with multiple new product candidates. And most important of all, in this past year, I'd like to say we saved the life of Mr. Bennett with a 10-gene XenoHeart. We saved the lives of at least 100 children stricken with neuroblastoma thanks to our Unituxin medicine. We have now saved over 200 lives of lung transplant patients by increasing the usable donor lung supply with our lung bioengineering technology. And we have saved or improved the lives of thousands of pulmonary hypertension patients in the past year with our Remodulin, Remunity, Tyveso, and Arenatran products. From the headline saving of one life, to the kind of like prayers granted saving of 100 children's lives, to the now almost routine saving and improving of thousands of lives, I can most confidently report that UT's first year as a public benefit company has been super true to our public benefit purpose. Mike, can you lead us off now with commercial operations?

Sure. Thanks, Martine. And good morning, everybody. As Martine said, we're very pleased to have posted double-digit revenue and patient growth for the full year of 2021, ending the year with more than 10,000 patients on one of our terprocinal therapies. This quarter, I'd like to dive into the underlying performance of our three terprocinal products, Tyveso, Remodulin, and Arenatran. As usual, I'm going to focus more on our patient metrics, and I'll remind everyone that our quarterly terprocinal revenue does not always track exactly with quarterly underlying patient demand due to our specialty pharmacy partner ordering patterns. So I'll begin with Tyveso. As you may recall, in early 2021, we established a goal to double the number of patients on Tyveso from approximately 3,000 when the PHILV indication was added to the label to 6,000 by the end of 2022. This assumes no COVID-related impact to physician access and patient initiation of therapy and importantly recognizes that our path to doubling may not be linear. The fourth quarter was our third quarter of the PHILD launch. And in this quarter, we had the highest number of Tyveso referrals, which is what we call prescriptions, since launch. And we added close to 300 patients to our Tyveso active patient census. Our new patient starts were less than Q3, which is common in the fourth quarter, as many patients opt to wait until after the holidays to begin advanced therapies. Our specialty pharmacy partners are working to clear this backlog and get these patients started on therapy during the current quarter. We continue to anticipate a CMS coverage decision regarding Medicare reimbursement for Tybaso and PHILD anytime between now and May of this year. All the necessary steps have been completed, including the close of a public comment period last year. We can't predict the timing of this coverage decision, but in the meantime, federal healthcare patients still have the opportunity to apply to our patient assistance program to access tibiasal therapy prior to the coverage decision if they are eligible. We anticipate three core drivers for continued tibiasal growth over the next several quarters. I think I mentioned these on the last call. First, we think the CMS coverage decision and PHILD will be a driver for tibiasal growth through the middle of this year. Even though federal healthcare patients may apply for our patient assistance program, we are hearing through the channel that many physicians are simply waiting for CMS coverage before prescribing Tyveso in their PHILD patients. Second, we continue to grow the Tyveso prescriber base, particularly among ILD treaters, and expect to see continued growth of prescriptions from these physicians over the next two quarters and beyond as we continue our outreach and educational efforts in this space. Up until now, the vast majority of Tyveso prescribing has come from historical PAH, so there is a lot of as-yet untapped potential in this area. And finally, we view the upcoming Tyveso DPI approval as an additional catalyst to Tyveso growth. While we would have been thrilled with an FDA approval for Tyveso DPI this week, as we said in our Q3 call, we've been assuming a launch by summer of this year, so nothing's really changed in that regard. In the meantime, we are completing our launch preparations, and we will be ready to launch immediately upon approval. Moving to Orinatram, we saw yet another quarter of record patient counts during the fourth quarter. As we've discussed before, we believe its uptake is driven by the Freedom EV label expansion now that we're able to have more robust interactions with prescribers about the data. And finally, we're pleased with the continued strong performance of Remodulin despite the launch of a generic form of subcutaneous tryprosinol last year. That generic launch has continued to play out closely with what we saw with the IV generic launch in 2019, with an initial bolus of patients, primarily those dual-eligible Medicare-Medicaid patients, transitioning to the generic tropostinol, trickling down to an immaterial number of generic transitions in recent months. The feedback we've received on our immunity pump has been quite positive in our early launch efforts. As part of that feedback, we learned that the pump's alarms can, in some cases, be overly sensitive. To be clear, the issues we're seeing with the alarms are not safety issues. But to ensure that physician and patients have an awesome experience with the pump, we recently paused the introduction of new patients to Rimmunity while we work with our partner, DECA, to optimize the alarm profile. We just completed final testing of the new alarm system. Everything is working as expected, and we will recommence our Rimmunity rollout next week. To wrap up, we're pleased with the progress with Tyveso and PHILD. We look forward to a CMS coverage decision in May or earlier. Likewise, we're on track to achieve our 6,000 patients on Tyvesa by the end of the year, and we're pleased with the continued momentum for Renatran. Finally, we think that our remodeling revenues will remain robust despite generic competition, especially once we recommence the introduction of new patients to the Remunity Pub. And with that, I'll turn the call back over to Martine.

Thanks so much, Mike. Super exciting about the Remunity Pub. I'm on breakout next week. Awesome. So, operator, I understand that you probably have some people in queue and feel free to bring them on.

Thank you. At this time, I would like to remind everyone in order to ask a question, press star and the number one on your telephone keypad. Your first question today comes from the line of Joseph Stone with Cowan & Co. Your line is now open.

Good morning. Thank you for taking my question and congrats on the progress. Maybe just on the Tyvaso DPI request by the FDA, are you able to provide a little bit more information as to the type of information that you submitted? And then in terms of the safety profile you've seen with Tyvaso DPI to date, some high-level thoughts there, especially as it relates to potential for bronchospasm. Thank you.

Yeah, thanks, Joe. We've really had some you know, absolutely great experience with the Tyveso DPI to date, and we have not experienced those bronchospasm side effects that you referred to. So, we really don't believe that that's going to be an issue at all. There is some more information in the press release. If you look down toward the second or so page of the press release, there will be a little bit more information there about the submission and what was submitted and not submitted. So I think it's all really quite routine and the FDA doing their job as best that they can. As I mentioned in my introductory remarks, And as Mike emphasized in his remarks, three months is really meaningless in the context of this product's life. This product has a very long path in life. It is an amazing product. I mean, it's so convenient and easy for the patients to use. We have the great results of the BREEZE trial. It's going to end up being used, I'm confident, by thousands and thousands and And over the course of its life, you know, like 10,000 more or more patients. It's just an amazing product. So it'll get out there. You know, everybody just has to make sure that, like, all the boxes are checked and the I's are dotted and the T's are crossed. And as Mike said, we feel confident with the launch by the timeframes that we've previously guided everyone to. All righty, Joe, thanks for the question. And, operator, you can bring up the next one.

Your next question today comes from the line of Yin Yang with Jefferies. Your line is now open.

Thank you. Another question on DPI. Once it's approved, does it need to go through a CMS approval process similar to the PHR indication for Medicare coverage?

Oh, very. Thank you, Yin. So nice to hear your voice this morning. You know, I think we have a lot of experts on our call, but I think Mike Bankowitz would be the best person to respond to your question. Mike, if that's okay? Sure.

I'm happy to take that question. So there is a CMS approval process that will need to happen, a review process that will need to happen with Tyveso DPI, but it's different than what we're experiencing with PHILD. So for PHILD, I'm sorry, yeah, for PHILD. So, you know, right now PHILD is approved. for use with our TD 300 nebulizer. And it's covered in the medical benefit or Part B side, B as in Boy side of Medicare. The DPI will be a pharmacy benefit product, so covered in Part D. So the process is a little different. So while Medicare is reviewing the data, reviewing the product for coverage, patients can still access, federal health care patients can still access a DPI. The physician simply has to go through an appeal process, and they're accustomed to doing this. They have to do this often with products that aren't on Medicare formulary, and it's just an extra step they have to go through, and then it gets approved. So we won't see this same issue we're seeing with PHILD where we have this holdup with the DPI. Those will continue to go through with doctors, like I said, doing this additional step of appealing.

Perfect. Thank you so much, Mike. Operator, who would be our next questioner?

Your next question today comes from the line of Jessica Bai with J.P. Morgan. Your line is now open.

Hey there. Good morning. Thanks for taking my question. Curious what proportion of Tyveso patients are currently on free drug. And what are the next clinical or manufacturing milestones we should look out for in the organ transplant business? And what results in your mind would justify un-gating the potential investment in the first GMP or GMP-like manufacturing facility for those products?

Great, Jess. So happy to hear you on the call. We think of you as like one of the KOLs of pharmaceutical analysts, so it's always exciting to hear your voice here. I think the first part of your question is probably best answered by Mike, and then, Mike, if you bounce it back over to me, I'll then talk about the Zeno aspects of just this question.

Sure. This question has come up, I think, a couple times over the last year, so as a baseline, There's always a small percentage, I would say kind of low to mid single-digit percentage of patients that are in our patient assistance program at any point in time. With us needing to wait for the CMS coverage decision on PHILD, That has continued to increase. And so, you know, I think on the last call I had reported that it was getting up into kind of the higher single digits, about to cross over into double digits. We've now crossed over into double digits. You know, so it's double-digit percentage of patients, but it's on the low end of double-digit percentage.

Perfect. Martine? Yeah, that's great, Mike. Oh, Jess, it's really interesting, the launch of these new Xeno products. And we have in our call, in fact, Dr. Peterson. She is our Senior Vice President for Product Development, and she will be leading the effort now to take those products through their clinical development process. We also have on the call Pat Poisson, who is our Executive VP for Technical Operations. And then people underneath him who right now are responsible for manufacturing our biologic product such as unituxin, they will be responsible for manufacturing this new type of biologic, the xenografts, be they the U-heart, the U-kidney or the U-thymokidney. So all of that is very much moving into the clinical development phase. And it's super exciting doing the things like, you know, identifying the clinical trial centers, identifying the clinical investigators, putting together the necessary protocol, having, you know, the meetings with the FDA to get buy-in to the protocol and the clinical development. Our biostatisticians are already computing the necessary clinical trial parameters So everybody is kind of rowing their oars in the same direction toward those clinical development and gating milestones for those products. So I think you're going to see all of that in the near term. And in between, you may hear of certain kind of expanded access opportunities that arise, such as with... the case of Mr. Bennett, where there's a possibility for a leading surgeon at a leading hospital to uniquely save somebody's life through the unique advantages of these xenografts. So I think you'll see some of that as well. In the case of Mr. Bennett, there were no other alternatives. And here he is, you know, almost two months out, no sign of rejection. I just could not be more proud of all of the efforts of our group at Revivacor, how they were able to, you know, carefully splice in all of these different 10 genes to make that heart. In the words of Dr. Griffith, the transplant surgeon, he keeps telling me, Martin, this heart is a rock star. And this is the guy who's like, you know, did the second Jarvik heart. I mean, he really knows his stuff. And in the words of, for example, Dr. Montgomery at NYU, he is just so impressed with the, you know, sorry to get a little bit graphic here, but like the urine produced by the xenokidney, super, super impressed with it. Dr. Locke, the head of transplant down at UAB, she's placed her xenokidneys into... Mr. Parson was one of the decedent donors, orthotopic positions for the kidneys. She's done another similar type of xenokidney transplant and in both cases is just super, super pleased with the outcome. So this xenotransplantation train has definitely, definitely, definitely just left the station. And I think you're going to see some really exciting ungating of the clinical development and production spending, capital expansion opportunities right up ahead. Operator, it looks like we have one more question in line.

Yes, your next question comes from the line of Andre Argarides with Wedbush Securities. Your line is now open.

Good morning and thanks for taking our question. Before I get into questions, just congrats on the quarter and all the life-saving progress that you've made. It's a true testament to your dedication to it. So, you know, we appreciate that too. So just continuing on the, you know, transplantation, Could you maybe give us a little bit more color around how you think or what the next kind of major milestone would be in these programs? Is it six months out? And then, you know, looking at DPI approval, how are you looking at that launch contributing to or the potential launch contributing to growth of patients on Tybeso this year and next year as well. Thank you.

Thank you so much, Andreas, for the questions, and thank you for the recognition of us doing our best with our public benefit purpose. Mike, if I could call on you again to answer first the DPI-related question, and then I'll follow up with the Xeno-related question.

Sure. So on the DPI launch, As I said in my opening remarks, we'll hear back from the FDA in May, assuming that's an approval and we're ready to go, ready to launch. We have everything in place and ready to go. We'll have inventory, plenty of inventory. We actually had our launch meeting with our sales team this week, so they're prepped and ready to go. And so we'll be able to really press play on our launch once we hear back from the FDA. And we do think that there's in both PHILD, as I mentioned, to accelerate growth there, as well as PAH. There's really, I think, a lot of excitement and enthusiasm around the Tyvesa DPI, and I think it really is going to create an opportunity for us to expand the number of patients that we're able to help with prostacyclin therapy and PAH, as well as PHILD, as I said. So we look at that as being a significant contributor there. to our marked 25,000 patients by the end of 2025. As Martine said, it should be a blockbuster drug. That's certainly how we view it and how we're planning to approach it from a watch perspective.

Thanks so much, Mike. Andreas, with regard to the next thing that you might hear about, it's I think that, you know, there is a pretty good likelihood that there will be some sort of an announcement. And again, you know, knock on wood and, you know, cross my fingers that Mr. David Bennett Sr. continues to do well at like the 90 day and the six month mark. And the reason I call those out is when the FDA looks at clinical transplantation milestones, they put a lot of emphasis on sort of like two weeks, 30 days, 60 days, 90 days, and maybe one year. And we know this because one of our phase three trials, for example, which relates to the over 200 lives we've saved with our lung bioengineering technology, relates to getting clinical FDA approval for our second trial. lung bioengineering technology, which is wrapping up its last couple of patients of its phase three trial. And with this type of technology, which is kind of techno-speak, it's called ex vivo lung perfusion technology, the FDA wants to see that the patients who are on our lung bioengineering technology do as well at two weeks, four weeks, three months, six months, etc., as the patients who don't have the advantage of the lung bioengineering technology. So that same kind of milestone metrics, I think, are going to apply in the xeno context. And our goal would be to show that our xenograft patients, of course, separately for kidneys and hearts, do as well at two weeks, four weeks, three months, six months, and a year, as would patients who are otherwise similarly matched but have allografts. Now, you know, depending on the organ, the slope is pretty severe. You know, even with something that has been done for decades, like alloharp transplants, you're looking at, you know, you know, 80% to 90% survival in one year, which, you know, depending if you're looking at the glass half full or half empty, it's like amazing, these lives were saved. But, you know, oh, my God, can't we do better and not lose, you know, 10% to 20% of the people? And for things like lungs, for example, unfortunately, the curve is worse. For kidneys, it's better. Another advantage with kidneys is you can always, you know, back up. to have the patient on dialysis. So that's an advantage. A huge advantage for Zeno is that there's pretty much consensus agreement around the experts in the field that people who have rejected a previous kidney transplant and have a lot of reactive antibodies in their blood, that those do not cross-react with Zeno antigens. So a person who has already had a kidney transplant would have a much, much tougher climb to try to get another kidney transplant, but would not likely have the same aggressive reaction to another allotransplant, I mean, to a xenotransplant as they would have had a very aggressive reaction to another allotransplant. So that's a kind of a favorable patient category. There's also about 80% of the people who are on dialysis in the U.S. do not even qualify to be on the kidney transplant list. So that's another huge patient population. Then there are patients who have been on dialysis for so long that they have actually pretty much run out of access ports in their body for dialysis. And that becomes increasingly problematic for those patients. So there are just many, many different opportunities to insert xenotransplantation into the transplant paradigm. And we are going to do it, and we're going to follow the same clinical milestones that you've seen the FDA previously require, such as two weeks, 30 days, 60 days, 90 days, et cetera, as for allotransplantation. Well, I see that we're at the half-hour mark here. So thank you, Andreas, very much for your questions. Thank everybody. Operator, or thank you, Dean. And do you want me to turn it back to you or to the operator?

I'll turn it to the operator.

Okay. Operator, it's all yours.

Thank you for participating in today's United Therapeutics Corporation Earnings Webcast. A rebroadcast of this webcast will be available for replay for one week by visiting the events and presentation section of the United Therapeutics Investor Relations website at ir.unither.com. Thank you. You may now disconnect.