Q4 2023 United Therapeutics Corp Earnings Call

Operator: Good morning and welcome to the United Therapeutics Corporation fourth quarter 2023 earnings webcast. My name is David, and I will be your conference operator today. All participants on the call will be in listen-only mode until the question-and-answer portion of the earnings call.

Good morning, and welcome to the United Therapeutics Corporation fourth quarter 'twenty twenty-three earnings webcast. My name is David and I will be your conference operator today, all participants on the call.

David: The webcast will be in listen only mode.

David: Until the question and answer portion of the 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.

Operator: If you would like to ask a question during that time, simply press star, then 1 on your telephone keypad. If you would like to withdraw your question, please press star, then 2. Please note this event is being recorded. I would now like to turn the conference over to Dewey Steadman, Head of Investor Relations at United Therapeutics. Thank you, Dave. And good morning.

David: Please note. This event is being recorded I would now like to turn the conference over to Dewey Steadman head of Investor Relations at United Therapeutics.

Dewey Steadman: Thank you, Dave and good morning, It's my pleasure to welcome you to the United Therapeutics Corporation fourth quarter 2023 earnings webcast.

Dewey Steadman: It's my pleasure to welcome you to the United Therapeutics Corporation fourth quarter 2023 earnings webcast. 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. We assume no obligation to update those forward-looking statements.

Dewey Steadman: 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.

Dewey Steadman: Our latest SEC filings, including forms 10-K, and 10-Q contain additional information on these risks and uncertainties, we assume no obligation to update those forward looking statements.

Dewey Steadman: 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 use. Full prescribing information for the products is available on our website.

Dewey Steadman: His remarks also may discuss the progress when we felt from clinical trials or other developments with respect to our products. In these remarks are intended so at least 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 volt.

Dewey Steadman: Full prescribing information for the products are available on our website.

Dewey Steadman: Accompanying me on today's call are Dr. Martine Rothblatt, our Chairperson and Chief Executive Officer, Michael Bigwoods, our President and Chief Operating Officer, James Edgemond, our Chief Financial Officer and Treasurer, Dr. Lee Peterson, our Executive Vice President of Product Development and Xeno-Transplantation, and Pat Poisson, our Executive Vice President of Technical Operations. Note that James and I will be participating in one-on-one meetings at the 2023 UBS European Healthcare Conference on February 27th in London. Michael James and I will participate in a fireside chat and one-on-one meetings at the TD Cowan Healthcare Conference on March 5th in Boston.

Speaker Change: Accompanying me on today's call are Dr. Martine Rothblatt, our chairperson and Chief Executive Officer, Michael Baker, Our President and Chief Operating Officer, James <unk>, Our Chief Financial Officer, and Treasurer, Dr. Leigh Peterson, our executive Vice President of product development, and Zeno transplantation and pathways on our executive Vice.

Speaker Change: Technical operations.

Speaker Change: Note that James and I will be participating in one on one meetings at the 2023 UBS European Health Care Conference on February 27th in London, Michael Janssen, I will participate in a fireside chat and one on one meetings at the TD Cowen Health Care Conference Edmar Arent March 5th in Boston and Pat.

Dewey Steadman: And Pat Poisson and I will participate in a fireside chat and one-on-one meetings at the Learning Partners Global Biopharma Conference on March 12th in Miami. Our scientific, commercial, and medical affairs teams will present at the American College of Cardiology 73rd Scientific Sessions, April 6th through 8th in Atlanta, the International Society for Heart and Lung Transplantation, April 10th through 13th in Prague, and the American Thoracic Society International Conference on May 17th through 22nd in San Diego. And now I will turn the call or the webcast over to Dr. Rothblatt for an overview of our fourth quarter 2023 financial results and the business activities of United Therapeutics. Martine?

Speaker Change: Finally, I will participate in a fireside chat and one on one meetings at the Leerink partners Global Biopharma Conference on March 12 in Miami.

Speaker Change: Our scientific commercial and medical affairs teams will present at the American College of Cardiology, 73rd Scientific sessions April 6th through eighth in Atlanta, The International Society for Heart and lung transplantation April 10th through 13th in Prague, and the American Thoracic Society International Conference on May 17, 2%.

Speaker Change: Second in San Diego.

Speaker Change: And now I will turn the call or the webcast over to Dr. Rothblatt for an overview of our fourth quarter 2023 financial results and business activities of United Therapeutics Martine.

Martine A. Rothblatt: Thank you, Dewey. Good morning everyone, and a good day to those who are on the other side of the ocean. Congratulations to the 1,200 Unitarians who work tirelessly every day to help us achieve our third straight quarter of record revenue and our second straight year of record revenue; we yet again achieve 20% plus quarterly and annual revenue growth for the fourth quarter and the full year 2023. On top of our record performance in the fourth quarter of 2023, earlier this year, we received important external validation of the value of our Tyvaso DPI business through a royalty transaction executed by our partners at To put it simply, mankind sold a tenth of their 10% loyalty payments streamed from us, which equates to 1% of Tyveso DPI sales, and they sold it to Sagar Healthcare Partners for $150 million plus other milestones. That implies an external valuation of the entirety of the Taiweso DPI revenue stream of $15 billion before even factoring in the additional potential milestone.

Martine A. Rothblatt: Thank you Julie good morning, everyone and good day to those who are on the other side of the oceans.

Martine A. Rothblatt: Congratulations to the 1200 units areas, who work tirelessly everyday to help us achieve our third straight quarter of record revenue and our second straight year of record revenue.

Martine A. Rothblatt: Yet again achieved 20% plus quarterly and annual revenue growth for the fourth quarter and the full year 2023.

Martine A. Rothblatt: On top of our record performance in the fourth quarter of 2023 earlier. This year, we received important external validation of the value of our Thai VSO DPI business through a royalty transaction executed by our partners at Mannkind Corporation.

Martine A. Rothblatt: To put it simply mankind sold attempt of their 10% royalty payment stream from us, which equates to 1% of Taipei, So DPI sales and they sold it to safeguard health care partners for $150 million plus other milestones.

Martine A. Rothblatt: That implies an external valuation of the entirety of the Thai VSO DPI revenue stream of $15 billion before even factoring in the additional potential milestones.

Martine A. Rothblatt: That's well above the current market cap for our entire business. And importantly, this transaction valuation is far above the Wall Street valuation of our entire company as a whole and is for only one of our many products. At United Therapeutics, we talk about being positioned for three waves of growth. And let's dive into the many reasons why we're so confident in our business. Our first wave of growth will come through our existing commercial business led by Taibaso in PHILD. We continue to post solid growth in our current business, with our third consecutive quarter of record revenues for Kaideso and revenue growth for our U.S. Vermodulin business despite the presence of competition on the market for the past five years. Our growth in PHILD and continued leadership in pulmonary arterial hypertension, also known as PAH, has led our nebulized Tybaso and our Tybaso DPI products to become the most prescribed prostacyclin therapy in the United States. Michael will go into detail on this exciting aspect of our commercial business. Our second wave of growth will come from our near-term pipeline, led by the Teton studies in pulmonary fibrosis and the advanced outcome study of Relenopag in PAH. These programs should enable us to continue our double-digit annual growth trend through the second half of the decade.

Martine A. Rothblatt: That's well above the current market cap.

Martine A. Rothblatt: Our entire business.

Martine A. Rothblatt: Yeah.

Martine A. Rothblatt: And importantly this.

Martine A. Rothblatt: This transaction valuation is far above the wall Street valuation of our entire company as a whole and as for only one of our many products.

Martine A. Rothblatt: At United Therapeutics, we talk about being positioned for three waves of growth and let's dive into the many reasons why we're so confident in our business.

Martine A. Rothblatt: Our first wave of growth will come through our existing commercial business led by high base. So in ph ILD.

Martine A. Rothblatt: We continue to post solid growth in our current business with our third consecutive quarter of record revenues for <unk> and revenue growth for our U S modular business. Despite the presence of competition on the market for the past five years.

Martine A. Rothblatt: Our growth in ph ILD and continued leadership in pulmonary arterial hypertension also known as P. H has led our nebulizer high base. So MLR Thai based on DPI product combining to become the most prescribed prostacyclin therapy in the United States.

Martine A. Rothblatt: Michael will go into detail on these at this exciting aspect of our commercial business.

Martine A. Rothblatt: Our second wave of growth will come from our near term pipeline led by the Tee times studies in pulmonary fibrosis and the advanced outcome study of <unk> in P. H.

Martine A. Rothblatt: These programs should enable us to continue our double digit annual growth trend through the second half of the decade I will provide updates on the Teton and relenza peg programs shortly.

Martine A. Rothblatt: I will provide updates on the Teton and the Lenapeg programs shortly. Of course, both our first and second waves of growth are subject to clinical trial outcomes, regulatory approvals, new competitive entrants, and the potential impacts of the Inflation Reduction Act. But we feel good about our prospects for meeting these revenue growth targets. Our third wave of sustainable growth will come through the development, manufacture, and widespread use of manufactured organs and organ technologies to provide a solution to patients suffering from end-stage kidney, lung, heart, and liver disease. Now, moving to our near-term pipeline and second wave of growth, we have four key registration trials underway, three Teton studies for pulmonary fibrosis and the Advanced Outcomes Study for Relenopag and Oral Therapy for Group 1 PAH.

Martine A. Rothblatt: Of course, both our first and second waves of growth are subject to clinical trial outcomes regulatory approvals, new competitive entrants and the potential impacts of the inflation reduction act, but we feel good about our prospects for meeting these revenue growth targets.

Martine A. Rothblatt: Our third wave of sustainable growth will come through the development manufacture and widespread use of manufactured organs and Oregon technologies to provide a solution to patients suffering from end stage kidney lung heart and liver disease.

Martine A. Rothblatt: Now moving to our near term pipeline and second wave of growth. We have four key registration trials underway three key time studies for pulmonary fibrosis and the advanced outcome study for Brilinta pegged an oral therapy for group one H.

Martine A. Rothblatt: We also advanced our mural liver elap program toward the clinic with a recent and historic IND clearance by the FDA. Moving to Teton, we believe IPF represents a 100,000 patient opportunity in the United States with only two approved therapies that nearly slow lung function decline. Both Teton 1 and Teton 2 are enrolling patients, and at this time, we are aiming for full enrollment in both studies with 576 patients each by the end of this calendar year. Likewise, we believe PPF, or progressive pulmonary fibrosis, represents a 60,000 patient opportunity in the U.S. alone, and this disease is quite distinct from IPF, or idiopathic pulmonary fibrosis.

Martine A. Rothblatt: We also advanced our miro liver either have program toward the clinic with our recent and historic R&D clearance by the FDA.

Martine A. Rothblatt: Moving to <unk>, we believe IPF represents a 100000 patient opportunity in the United States with only two approved therapies that nearly slow lung function decline both <unk>, one and <unk> two are enrolling patients.

Martine A. Rothblatt: And at this time, we are aiming for full enrollment in both studies with 576 patients each by the end of this calendar year.

Martine A. Rothblatt: Likewise, Likewise, we believe P. P F R <unk>.

Martine A. Rothblatt: Progressive pulmonary fibrosis represents a 60000 patient opportunity in the U S alone and this disease is quite distinct from IPF or idiopathic pulmonary fibrosis. One of the two FDA approved IPF therapies is also approved for PPE.

Martine A. Rothblatt: One of the FDA-approved IPF therapies is also approved for PPF, and as in IPF, it only slows the decline of lung function in these fragile patients. The Teton PPF study will start its first patients in the fourth quarter of 2023, right on schedule, and we expect this trial to enroll 698 patients. We believe there is a high probability of success in the three Teton studies based on the IPF subset analysis of the increased study of nebulized tybaso in PHILD patients. Unlike the two IPF studies that are already on the market, nebulized plibaso, at a safety endpoint, showed an improvement, an improvement, actual improvement of lung function in the subset of patients that had IPF That just gives so many people so much hope.

Martine A. Rothblatt: Yes.

Martine A. Rothblatt: And as in IPF, it only slows the decline of lung function and these fragile patients.

Martine A. Rothblatt: Pecan PFS study dose the first patients in the fourth quarter of 2023 right on schedule and we expect this trial to enroll 698 patients.

Martine A. Rothblatt: We believe there is a high probability of success in the <unk> studies based on the IPF subset analysis of the increased study of <unk>.

Martine A. Rothblatt: In ph ILD patients. Unlike the two IPF studies that are already on the market Nebulize Thai base, though in a safety endpoint showed an improvement an improvement actual improvement of lung function in the subset of patients that had IPF along with their pulmonary hypertension.

Speaker Change: That's that's just give so many people so much hope.

Martine A. Rothblatt: Now, let's move on to Relenopag and our Advanced Outcomes Study in Group 1 PAH, which continues to enroll patients, and we expect completion of the study in 2025. We are, in fact, targeting 700 to 1,000 patients in this study depending on the pace of accruing clinical worsening events. Belenopeg is a next-generation, selective, and potent prosthesis and receptor agonist that we are developing as a once-daily oral therapy for PAH. We believe Rolenapeg's once-daily dosing, sustained release profile, and titratability could position it favorably against the other oral prostacyclin receptor agonists on the market, as well as other therapies for PAH patients Relenopeg provides 24-hour coverage with higher potency than the other oral prostacyclin agonists, as demonstrated by in vitro assays, and Relenopeg significantly demonstrated more than 20% improvement in pulmonary vascular resistance in a phase 2 study.

Speaker Change: Now, let's move on to relent on peg.

Speaker Change: And our advanced outcome study in group, one ph, which continues to enroll patients and we expect completion of the study in 2025. We are in fact targeting 700 to 1000 patients in this study depending on the pace of accruing clinical worsening event.

Speaker Change: The Atlanta Peg is a next generation selective and potent prostacyclin receptor agonist, which we are developing as a once daily oral therapy for PIH, we believe relented pegs once daily dosing sustained release profile and titrate ability.

Speaker Change: <unk> could position us favorably against the other oral prostacyclin receptor agonist in the market as well as other therapies for ph patients well.

Speaker Change: <unk> provides 24 hour coverage with higher potency than the other oral prostacyclin agonist as demonstrated by in vitro assays and relented peg significantly demonstrated more than 20% improvement in pulmonary vascular resistance in a phase III study.

Martine A. Rothblatt: A long-term phase two open-label study of Relenopeg also showed sustained improvement in six-minute walk distance for more than two years. A manuscript recently published in the journal Advances in Therapy describes these exciting findings. Now, while we and others have made progress extending lives and improving patient outcomes through troprosinol and other therapies, the only known cure for PAH remains a lung transplant. That also is the case for IPX.

Speaker Change: Our long term phase two open label study of <unk> also showed sustained improvement in six minute walk distance out to more than two years.

Speaker Change: Manuscript recently published in the journal advances in therapy describes these exciting findings.

Speaker Change: Now, while we and others have made progress as extending lives and improving patient outcomes through to a proximal and other therapies. The only known cure for PHH remains a lung transplant.

Speaker Change: That also was the case for IPF.

Martine A. Rothblatt: The problem for PAH, IPF, and many other patients with end-stage organ disease is that there aren't enough donors and transplantable organs available to address the need. And for many organ donations, one life sadly must be lost to save another. We believe the best solution to this problem is to create a supply, an unlimited supply, of tolerable, transplantable, manufactured organs. Even better, with an unlimited supply of organs, transplantation can become a consideration for therapy in countless end-stage organ diseases for which there are few good treatment options. Accordingly, we have been developing several investigational approaches using multiple technologies with different organs, all with this same goal in mind. The first is our Ex Vivo Lung Perfusion Service, or EVLP, which has led to over 380 lives saved with lungs that have undergone EVLP in our facilities in Silver Spring, Maryland, and at the Mayo Clinic Jacksonville campus. Beyond EVLP, we have four platforms: xenotransplantation, regenerative medicine, 3D bioprinting, and bioartificial organs. These four platforms cover four key organs: lung, heart, kidney, and liver.

Speaker Change: Problem for ph IPF and many other patients with end stage organ disease is that there arent enough donors and transplantable organs available to address the need and for menu organ donations.

Speaker Change: Life, Sadly must be lost to favor lager.

Speaker Change: We believe the best solution to this problem is to create a supply an unlimited supply of tolerable transplantable manufactured organs, even better with an unlimited supply of Oregon's transplant can become a consideration for therapy in countless end stage <unk>.

Speaker Change: Diseases for which there are few good treatment options.

Speaker Change: Accordingly, we have been developing several investigational approaches using multiple technologies with different organs, all with the same goal in mind.

Speaker Change: First is our ex vivo lung perfusion service or <unk>, which has led to over 380 lives saved with ones that have undergone <unk> in our facilities in silver spring.

Speaker Change: Maryland and at the Mayo Clinic Jacksonville campus.

Speaker Change: Beyond <unk>, we have four platforms Zeno transplantation regenerative medicine, three D bio printing and bio artificial organs. These four platforms cover four key organs lung heart kidney and liver.

Speaker Change: Starting with Zeno transplantation, we continue to work with the FDA on the clinical path forward.

Martine A. Rothblatt: Starting with xenotransplantation, we continue to work with the FDA on a clinical path forward. We're underway with what we call pivotal preclinical studies in baboons at the request of the agency, specifically for our 10-gene program. We expect the last preclinical xeno kidney transplant to occur in the first half of 24. We expect to meet with the agency later this year to discuss the IND and clinical protocol for human studies for our 10-gene xeno-organ. In parallel with the pivotal preclinical studies, the construction of our clinical scale designated pathogen-free facility, or DPF, in Virginia is complete. And we dedicated the facility earlier this month.

Speaker Change: Underway with what we call pivotal preclinical studies in baboons at the request of the agency specifically for our 10 Gene program. We expect the last preclinical Zeno kidney transplant to occur in the first half of 'twenty four.

Speaker Change: We expect to meet with the agency later this year to discuss the IMD and clinical protocol for human studies form 10 gene Zeno organs.

Speaker Change: In parallel with the pivotal preclinical studies the construction of our clinical scale designated pathogen free facility or DPF in Virginia is complete and we dedicated the facility earlier. This month, we expect the facility to begin receiving pigs, this quarter and for the facility.

Martine A. Rothblatt: We expect the facility to begin receiving pigs this quarter and for the facility to grow its population through the balance of 2024 in preparation for clinical studies in humans for both xenokidneys and xenohearts. Super, super exciting and, wow, just breathing so much hope into the entire transplant space. Last month, we received FDA clearance of our investigational new drug application that allows the neural liver ELAP system to enter human clinical trials. By the way, this non-registration study will be the first ever clinical study of a bioengineered organ. MiroLiver ELAP is an external liver assist product (ELAP) that is designed to provide liver support in the critical care setting. Acute liver failure is a devastating condition with no approved therapies.

Speaker Change: To grow its population through the balance of 2024 in preparation for clinical studies in humans for both vino kidneys and hearts.

Speaker Change: Super Super exciting and.

Speaker Change: Wow breathing.

Breathing so much hope into the entire transplant space.

Speaker Change: Last month, we received FDA clearance of our investigational new drug application that allows the miro liver elapsed system to enter human clinical trials.

Speaker Change: Either way this non registration study will be the first ever clinical study of our bioengineered organ.

Speaker Change: Zero liver lap is an external liver assist product or <unk> that is designed to provide liver support in the critical care setting.

Speaker Change: Acute liver failure is a devastating condition with no approved therapies, a liver transplant is often the only way to save these patients.

Martine A. Rothblatt: A liver transplant is often the only way to save these patients. The ELAP is intended to give the patient's liver a chance to heal itself, possibly reducing the need for liver transplantation. We look forward to providing more details on this program in the coming quarter. I'm thrilled that we're in such a great position at United Therapeutics. We have a solid commercial business posting record results with continued strong growth ahead, a pipeline of novel therapies that continue our strong double-digit revenue growth, and a long-term plan to address one of the largest, critical, unmet medical needs in medicine, all while helping our patients, employees, and shareholders succeed. I'll now turn the call over to our president, Michael Benkiewicz, who will give an overview of our commercial performance and expectations for potential competition Michael.

<unk> is intended to give the patient deliver a chance to heal itself, possibly reducing the need for liver transplantation.

Speaker Change: We look forward to providing more details on this program in the coming quarters.

Speaker Change: I'm thrilled that we are in such a great position at United Therapeutics, We have a solid commercial business posting record results with continued strong growth ahead, our pipeline of novel therapies that continue our strong double digit revenue growth and our long term plan to address one of the loss.

Speaker Change: Just critical unmet medical needs in medicine.

Speaker Change: While helping our patients employees and shareholders.

Speaker Change: T.

Speaker Change: I'll now turn the call over to our President Michael Banquet, who will give an overview of our commercial performance and expectations for potential competition. This year Michael.

Michael Benkiewicz: Thank you, Martine, and good morning, everyone. As Martine noted, today we reported our highest revenue quarter ever at $615 million, up 25% from the fourth quarter of 2022, and record annual revenues of more than $2.3 billion, up 20% over 2020. Importantly, we saw meaningful growth across our entire suite of products, like the Tybaso franchise, Remodulin in the U.S., Orenatran, and Unitex. Starting with the rent

Michael Banquet: Thank you Mark and good morning, everyone.

Michael Banquet: As Marty noted today, we reported our highest revenue quarter ever at $615 million up 25% from the fourth quarter of 2022 and record annual revenues of more than $2 3 billion up 20% over 2022.

Michael Banquet: Importantly, we saw meaningful growth across our entire suite of products at the <unk> franchise, where module in the U S. <unk> and you had a toxin.

Michael Banquet: Starting with our radar SRAM revenue of $84 million during the quarter was up 11% from the prior year. This growth reflects increases in volume price and average dose following the publication of.

Michael Benkiewicz: Revenue of $84 million during the quarter was up 11% from the prior year. This growth reflects increases in volume, price, and average debt. Following the publication of two peer-reviewed manuscripts in 2023, our medical affairs teams began providing education on data from the EXPEDITE study, which assesses the orenotram dose achieved after a rapid remodeling titration and then transition to orenotram. Worldwide remodeling revenue of $115 million for the fourth quarter was down 6% from last year, primarily impacted by international orders. However, U.S. remodeling revenue of $106 We expect this momentum to continue in the U.S. as we had a near record number of referrals and starts during the fourth quarter, driven in part by interest in the expedite study results. Worldwide Unituxin revenue of $54 million in the fourth quarter was up 48% from the prior year quarter, and U.S. Unituxin revenue of $49 million was up 34%.

Michael Banquet: Peer reviewed manuscript banished scripts in 2023, our medical affairs team to began providing education on data from the expedite study, which assess the array of trend dose achieved after a rapid reliable and titration and then transition to our restaurant.

Michael Banquet: Worldwide, where modular revenue of $115 million for the fourth quarter was down 6% from last year, primarily impacted by international order timing. However, U S for module and revenue of $106 million was up 9% from the fourth quarter of 2022.

Michael Banquet: We're module and both intravenous and subcutaneous remains the most prescribed parenteral prostacyclin in the U S. We expect this momentum to continue in the U S. As we had a near record number of referrals and starts during the fourth quarter driven in part by interest and the expedite study results.

Michael Banquet: Worldwide and effects on revenue of $54 million in the fourth quarter was up 48% for the prior year quarter and U S units Hudson revenue of $49 million was up 34%.

Michael Benkiewicz: U.S. growth was driven by price and volume, and these volume gains were driven primarily through a modest inventory build at our distributor. International ordering driven by our partner in Japan was strong over a comparably soft quarter in 2020. Finally, Tideso, worldwide Tideso revenue was up 45% to $351 million, our highest quarter ever. U.S. revenue was up 40% to $337 million and was the highest quarter ever.

Michael Banquet: U S growth was driven by price and volume in these volume gains were driven primarily through a modest inventory build at our distributor.

Michael Banquet: International ordering driven by our partner in Japan was strong over a comparably soft quarter in 2022.

Finally today so.

Michael Banquet: Worldwide <unk> revenue was up 45% to $351 million, our highest quarter ever.

Michael Banquet: U S revenue was up 40% to $337 million and was the highest quarter ever.

Michael Benkiewicz: U.S. growth in Tyvasia was led by the continued uptake of Tyvasia DPI. Tidasa Nebulizer and Tidasa DPI remain the number one prescribed prostacycline treatment in the U.S., and they remain the only approved therapies for PHILD. We're pleased to report that there were no material changes in inventories of Tybaso DPI at our specialty pharmacy distributors during the fourth quarter, and both distributors remain within their contracted inventory. The expansion of our partner Mankind's production capacity over the summer of 2023 continues to be sufficient to meet current demand, and a further expansion at Mankind is expected to come online in the coming months, which will allow us to reach as many as 25,000 patients per year Assuming normal production operations at Mankind, we do not expect any supply constraints moving forward. Interestingly, after the loss of Tyvaso DPI in May of 2022 and the subsequent expected decline in revenue for nebulized Tyvaso, we are starting to see modest sequential growth in U.S. nebulized Tyvaso revenue. A key reminder of the importance of the nebulizer for patients with pulmonary hypertension.

Michael Banquet: U S growth in <unk> was led by the continued uptake of <unk> ACO DPI.

Michael Banquet: So that would realize archived asa DPI or named the number one prescribed prostacyclin treatment in the U S and they remain the only approved therapies for ph ILD.

Michael Banquet: We're pleased to report that there were no material changes in inventories of <unk> DPI at our specialty pharmacy distributors during the fourth quarter and that both distributors remain within their contracted inventory levels.

Michael Banquet: The expansion of our partner mankind production capacity over the summer of 2023 continues to be sufficient to meet current demand and a further expansion at Mannkind is expected to come online in the coming months, which will allow us to reach as many as 25000 patients per year, what type of ACO DPI.

Michael Banquet: Assuming normal production operations at Mannkind, we do not expect any supply constraints moving forward.

Michael Banquet: Interestingly after the launch of <unk> DPI in May of 2022, and the subsequent expected decline in revenue for Nebulize. Today. So we are starting to see modest sequential growth in U S. Nebulize Taipei. So revenue a key reminder of the importance of the nebulizer for patients with pulmonary hypertension.

Michael Benkiewicz: Some physicians and patients continue to prefer the nebulizer because of its use profile or for reimbursement reasons. In addition, we are aware that some pulmonologists prefer to start and titrate their PHILD patients using the nebulizer before switching to Tyvasive DPI because this allows more precise titration in one breath increment, compared to the three-breath equivalent increments of Tyvaso DPI.

Michael Banquet: Some physicians and patients continue to prefer the nebulizer because of its use profile or for reimbursement reasons.

Michael Banquet: In addition, we are aware that some pulmonologists prefer to start and titrate their ph ILD patients using <unk> before switching to Titan ACO DTI.

Michael Banquet: It allows more precise titration in one breath increments compared to the three breath equivalent increments of <unk>. So DPI.

Michael Benkiewicz: We expect this platform strategy to emerge as a competitive advantage over other potential DPI products should they reach the market. Now, we've heard a lot about potential competition for tribasodpi, and I'd like to share several reasons why we're confident we will have the preferred dry powder inhaler for patients with PAH and PHIO. First, IVASA DPI requires only one breath per cartridge compared to two breaths for the potential companion

We expect this platform strategy to emerge as a competitive advantage over other potential DPI products should they reach the market.

Michael Banquet: Now we've heard a lot about potential competition for <unk> and I'd like to share. Several reasons why we're confident we will have the preferred dry powder inhaler for patients with ph and ph ILD.

Michael Banquet: First <unk> DPI requires only one breaths per cartridge compared to two <unk> for the potential competitor on top of that our low flow design requires less patient breath that the potential of high flow devices that may reach the market.

Michael Benkiewicz: On top of that, our low-flow design requires less patient breath than potential high-flow devices that may reach the market. In patients with compromised lungs, we think that the less breath required through a low-flow device will be seen as a fundamental benefit by both patients and prescribers. Finally, the low flow design of PIVASA DPI allows for consistent deep lung delivery.

Michael Banquet: In patients with compromised loans, we think that the less breadth required through a low flow device will be will be seen as a fundamental benefit by both patients and prescribers.

Michael Banquet: Next the low flow designer pervasive DPI allows for consistent deep lung delivery. This means means we can achieve similar blood levels as the nebulizer with less coprostanol than high flow devices.

Michael Benkiewicz: This means we can achieve similar blood levels as the nebulizer with less troprosinol than high flow devices. The DreamVote device for Tybasa DPI requires no cleaning or maintenance, saving patients time and effort compared to other potential devices that may reach the market. Also, TIDASO DPI is labeled for room temperature storage by patients, another important committee. There's no maximum label dose for Tybaso or Tybaso DPI, despite claims to the contrary by our potential competitors.

Michael Banquet: The dreamboat device for <unk>, Asa DPI requires no cleaning or maintenance saving patients time and effort compared to other potential devices that acreage to the market.

Michael Banquet: Also today, so DPI is labeled for room temperature storage by patients another important convenience point.

Michael Banquet: There is no maximum label dose for <unk> DPI, despite claims to the contrary by our potential competitors and finally, the brief study also demonstrated 98% patient satisfaction with tightening so to epi.

Michael Benkiewicz: And finally, the BREE study also demonstrated 98% patient satisfaction with Tyvaso DPI. These factors, coupled with the experience physicians have gained through the rapid uptake of Tyvaso DPI since launch, lead us to believe that Tyvaso DPI will compete as effectively with similar product offerings in the inhaled market as Remodulin has competed with similar offerings in the perinatal. Moving to the other potential competitor this year, the PAH community is anticipating the March FDA action date for the first potential active end signaling inhibitor for the treatment of Group 1 PAH. While we understand that there is some excitement for this new pathway, and we've seen this in the past with new offerings, it's important to remember that PAH is a complex, multifactorial disease where polytherapy is the norm, not the exception, and treating multiple pathways of the Based on the results of this new product's clinical trial and our conversations with prescribers, it does not appear that an active signaling inhibitor is either a cure for PAH or a replacement for process cyclin therapy.

Michael Banquet: These factors coupled with the experienced physicians have gained through the rapid uptake of today. So DPI since launch lead us to believe that tight ACO DPI will compete as effectively with similar product offerings in the handheld market as a module and S&P did with similar offerings in the peripheral market.

Michael Banquet: Moving to the other potential competitor this year the ph community is anticipating the March FDA action date for the first potential activating signaling inhibitor for the treatment of group one th, while we understand that there are some excitement for this new pathway and we've seen this in the past with new offerings, it's important to remember.

Michael Banquet: That PIH is a complex multi factorial disease, where poly therapy as the norm not the exception and treating multiple pathways of the disease aggressively on early is critical to patient outcomes.

Michael Banquet: Based on the result of this new products clinical trial, and our conversations with prescribers. It does not it does not appear that an accident signaling inhibitor as either a chair for PIH or a replacement for process cycle therapy. In fact in their pivotal trial, 70% of patients were on prostacyclin therapy with 40%.

Michael Benkiewicz: In fact, in their pivotal trial, 70% of patients were on prostacyclin therapy, with 40% on a parental prostacyclin-like hormone. Therefore, we see this therapy as additive to our existing prostacyclin patients. And if the activin signaling inhibitor helps further improve outcomes, then these patients should stay on our therapies longer. For those patients not yet on prostacyclin therapy, PAH is a progressive disease, and the vast majority of these patients will eventually need a prostacyclin, whether that's before or after initiating an active end signaling inhibitor will be case dependent.

Michael Banquet: On a parental prostacyclin, unlike our module.

Michael Banquet: Therefore, we see this therapy is additive to our existing prostacyclin patients and if the activin signaling inhibitor helps further improve outcomes in these patients to stay on our therapies longer.

Michael Banquet: For those patients not yet on a prostacyclin therapy.

Michael Banquet: <unk> is a progressive disease and the vast majority of these patients will eventually need a prostacyclin.

Michael Banquet: Whether thats before after initiate an activating signaling inhibitor will be case dependent but given that poly therapy is becoming the norm. We believe <unk> offers patients and prescribers a convenient way to cover the prostacyclin pathway earlier in a patient's disease journey.

Michael Benkiewicz: But given that TOLI therapy is becoming the norm, we believe Tybaso DPI offers patients and prescribers a convenient way to cover the process cycling pathway earlier in a patient's disease. Finally, we want to remind investors that this launch will only be in Group 1 PAH and will not affect our growing PAH ILD business where the active and signaling pathway has not yet been established. That brings us to the profile for proximal-based prostacyclines like Tybaso, Remodulon, and Anorexia. We have over two decades of use and safety data to support the use of troposinol in PAH patients. There is a correlation between process cyclin dose and patient outcomes. Teproxylin has demonstrated improvement across a wide array of key hemodynamic parameters, and no regular blood testing is required for process cyclin.

Michael Banquet: Finally, I want to remind investors that this launch will only be in groupon, PIH and will not affect our growing ph ILD business, where the activin signaling pathway has not been studied.

Michael Banquet: That brings us to the profile of <unk> based prostacyclin Lite <unk> out of out of trend.

Michael Banquet: We have over two decades of use and safety data to support the use of profitable and ph patients. There's a correlation between prostacyclin dose and patient outcomes to <unk> has demonstrated improvement across a wider what ryan wide array of key hemodynamic parameters and no regular blood testing is required for process cycle.

Martine A. Rothblatt: To wrap up, while we're entering a year of potentially increasing competition, we remain confident that we have the product portfolio, clinical data, support structures, and expertise to succeed in the emerging competitive landscape. We're extremely proud of our continued record performance in this past quarter and the entire year, and we think we're in the early stages of sustainable growth for our current commercial portfolio. With that, I'll turn the call back over to Martine to run it.

Michael Banquet: Muse.

Michael Banquet: To wrap up while we're entering the year potentially increasing competition. We remain confident that we have the product portfolio clinical data support structures and expertise to succeed in the emerging competitive landscape. We're extremely proud of our continued record performance in this past quarter and the entire year and we think we're in the.

Michael Banquet: Early stages of sustainable growth for our current commercial portfolio with that I'll turn the call back over to our team to run the Q&A.

Martine A. Rothblatt: Thanks, Mike. And congratulations again to you and your entire sales, commercialization, marketing, strategic operations, and allied health teams that have achieved, you know, sequential record quarters and years of growth in these products. It's just really beyond awesome.

Speaker Change: Thanks, Mike and congratulations again to you and your entire sales commercialization marketing strategic operations and Allied health teams that have achieved sequential record quarter.

Speaker Change: Quarters and years of growth in these products.

Speaker Change: Just literally beyond awesome. Thank you. So much operator, you can now open up the lines for any questions.

Operator: Thank you so much. Operator, you can now open up the lines for any questions. 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.

Speaker Change: We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone if youre using a speakerphone. Please pick up your handset before pressing the keys if at any time. Your question has been addressed and you would like to withdraw your question. Please press Star then two.

Operator: If at any time your question has been addressed and you would like to withdraw your question, please press star, then two. Our first question comes from Rowena Royce with Leelink Partners. Please go ahead. Hey, morning, everyone.

Speaker Change: Our first question comes from Rowena Ruiz with.

Rowena Ruiz: <unk> partners. Please go ahead.

Rowena Ruiz: Hey, good morning, everyone.

Michael Benkiewicz: So, I was curious if you could talk a bit about the underlying patient demand in the quarter for Tyvaso, both the DPI and the nebulizer, and any other key drivers that you're seeing. And I was curious, in terms of the big picture, are you seeing anything interesting in the inventory dynamics going into the first quarter this year? Thanks, Rona, for your question. It seems Mike would be the best person on the call to answer those questions. He did touch upon those points in his introductory remarks, but, Mike, maybe if you could provide a little bit more color. Sure, yeah.

Rowena Ruiz: So I was curious if you could talk a bit about the underlying patient demand in the quarter for Tony So both the DPI and nebulizer and any other key drivers that youre seeing.

Rowena Ruiz: And I was curious in terms of Big picture are you seeing any interest anything interesting in the inventory dynamics going into first quarter. This year.

Speaker Change: Thanks for your question.

Speaker Change: It seems Mike would be the best person on the call to answer those questions. You did touch upon those points in his introductory remarks, but Mike maybe if you can provide a little bit more color sure. Yeah, I think from a from an advanced standpoint for for the <unk> franchise, we're really happy with it.

Michael Benkiewicz: I think from an advanced standpoint for the Tyvaso franchise, we were really happy with what's, The demand metrics in the fourth quarter referrals came in at or above, I think, a record four quarter. New patients started, which is unusual given, you know, we talk a lot about the cyclicality and the seasonality, particularly in the fourth quarter with the holidays and the fewer shipping days. So, it was really nice to see that we were able to really kind of buck that trend on the referral side, and on the start side, we're pulling those through. One of the phenomena that I've talked about in past years with respect to the fourth quarter is that when referrals come in, sometimes between, particularly between that Thanksgiving and really end of year time period as people are settling into their holiday routines, patients are sometimes reluctant to start therapy.

Mike: But the demand metrics in the fourth quarter referrals came in at or above I think a record for us.

Mike: For quarter.

Mike: New patient starts which is which is unusual given you know we talk a lot about the cyclicality of the seasonality, particularly in the fourth quarter with the holidays and the fewer shipping days.

Mike: So it was really nice to see that we were able to really kind of bucked that trend on the referral side on the start side.

Mike: We're pulling those through one of the phenomena that I had talked about in past years with respect to the fourth quarter or is that when referrals come in sometimes between particularly between that Thanksgiving and really end of year time period as people are settling into their holiday routines patients a R. R.

Mike: Sometimes reluctant to start therapy, and so they'll delay.

Michael Benkiewicz: And so, they'll delay the start of the therapy until after the first of the year. And so, we did see a little bit of that on the start side. So, you know, record referrals, but, you know, the percentage of those that converted to starts within the quarter as compared to prior quarters was maybe down a little bit, but we're starting to see those pull through in the first quarter. So, again, that's not uncommon, and we see that typically every year.

Mike: The start of the therapy until after the first of the year and so we did see a little bit of that on the start side, so record referrals, but.

Mike: The percentage of those that converted to starts within the quarter as compared to prior quarters was maybe down a little bit, but we're starting to see those pull through with them.

Mike: The first quarter so.

Mike: Again, that's not uncommon and we see that typically.

Michael Benkiewicz: So, from a demand standpoint, just really, really happy with how the commercial teams are performing on the continued uptake of TIDASO DPI in both PAH and PHILD, and then generally the continued growth in the PHILD business. From an inventory standpoint, as Martn alluded to, and as I said in my opening remarks, I think we feel really good about where we are from an inventory standpoint. You know, Mankind, with the process and increased capacity improvements they made over the summer, they seem to be humming along, and so we're able to ensure that specialty pharmacy is staying within those contractual orders, and so that's been true, I think, for the last couple quarters now, and with more capacity coming on later this year, as I said earlier, we don't really expect there to be any type of supply constraints or anomalies on the Michael, thank you so much. Operator, next question.

Mike: For a year or so so from a demand standpoint, just really really happy with.

Mike: How the commercial teams are performing on the continued uptake.

Mike: Today's so DPI and both PAA and ph ILD and then generally the.

Mike: Continued continued growth on the ph ILD business.

Mike: From an inventory standpoint, as mark alluded to and as I said in my opening remarks, I think we feel really good about where we are from an inventory standpoint.

Mike: Mankind.

Mike: Process then.

Mike: Increased capacity.

Mike: Improvements they made over the summer.

Mike: They seem to be humming, along and so we're we're able to ensure that specialty pharmacy is staying within those contractual orders and so that's that's been true I think for the last couple of quarters now and.

Mike: With more capacity coming online coming out later this year as I said earlier, we don't really expect there to be any any.

Speaker Change: Any type of supply constraints or anomalies on the inventory side perfect. Michael. Thank you. So much operator next question.

Speaker Change: The next question comes from Ash Verma with UBS. Please go ahead.

Martine A. Rothblatt: The next question comes from Ash Verma with UBS. Please go ahead. Hi, congrats on the progress. Thanks for taking our questions. So maybe, just like starting off with Miro Liver, can you elaborate a little bit, like, what would the clinical study design look like?

Ash Verma: Hi, Congrats on the progress. Thanks. Thanks for taking my question. So maybe you can think a tightening up in the middle level or can you elaborate a little bit like what would the clinical study design look like.

Martine A. Rothblatt: And then second, in terms of the DPI out-of-pocket cost, with this year's implementation of the IRA catastrophic limit, would that normalize the out-of-pocket cost compared to the nebulizer, or would we start to see more of that benefit in 2025? Thanks. Okay Ash, it sounds to me like you had one question on the clinical trial design for the Zeno program and then you switched to a completely different topic on the IRA aspect. So why don't we start with Dr. Peterson sharing her thoughts on the clinical development way forward for Zeno, and then Mike can share some more thoughts about reimbursement issues. Dr. Peterson

Ash Verma: And then second in terms of the BPI out of pocket cost with this year with the IRT catastrophic gimmick implementation.

Ash Verma: What does that normalize the out of pocket costs compared to the nebulizer or would be start to see more of that benefit in 2025.

Speaker Change: Okay as it sounds to me like you had one question on the clinical trial design for the <unk> program, and then flip to a completely different topic on the IRI.

Speaker Change: So why don't we start with Doctor Peterson sharing her thoughts on the on.

Speaker Change: On the clinical development.

Doctor Peterson: Way forward for Zeno.

Doctor Peterson: And then Mike can share some more thoughts about reimbursement issues.

Dr Peterson: Dr Peterson.

Dr Peterson: Yes, Sir yes.

Dr. Lee Peterson: Yeah, sure. Yeah, for the Zeno program, with regard to our 10 gene Zeno kidney and 10 gene Zeno heart, we are continuing to conduct our IND enabling studies with our partners at the University of Maryland and Johns Hopkins. And we expect that these studies will finish, and we will start having meetings with FDA to actually discuss the specific clinical protocols for those programs with the intent of starting at least the 10 gene Zeno kidney study in 2025, and possibly the 10 gene Zeno heart. Okay, thanks, Dr. Peterson. And Ash, I think maybe I misheard a little bit in your trial question with regard to the ELAP study, and there I would refer you to what's posted at clintrials.gov. It is the first time ever that the FDA has approved a bioengineered organ for clinical trials. That's a humongous achievement, and great credit goes to Geoff Ross and his team at Mural Matrix for getting us to this point. So the details, that's a phase one safety study. You could read about it on the FDA's website.

Dr Peterson: For the for the lunar program with regard to our our 10 gene kidney in Tianjin Heart.

Speaker Change: We are continuing to.

Mike: Conduct our I N D, enabling studies with our partners at University of Maryland, and Johns Hopkins.

Mike: And.

Mike: We expect that these studies will finish and we will start having meetings with FDA to actually discuss the specific clinical protocols for those programs with.

Mike: With the intent of starting to at least the 10 gene kidney.

Mike: Kidney study and 2025 and as well all possible over time James Hart.

Speaker Change: Okay. Thanks, Dr Peterson.

Speaker Change: And.

James Hart: I think maybe I Miss heard a little bit in your <unk>.

James Hart: Final question.

James Hart: With regard to the <unk> study and there I would refer you to whats posted at Clinton trials Dot Gov. It is the first time ever that the.

James Hart: The FDA has approved a.

James Hart: A bioengineered organ in clinical trials.

James Hart: Humongous achievement in Great credit goes to Jeff Ross and his team at Bureau matrix for getting us to this point. So the details Thats a phase one safety study you could read it on the Fda's website, but we're.

Martine A. Rothblatt: But we're really excited, too, with so many pathways and platforms in our organ transplantation business to have the Mural ELAP serve in some ways as a pathfinder as we bring more and more types of manufactured organs into the clinic. Mike, do you want to chat about the IRA thing? Sure, happy to. So Ash, I think your question was about the changes to the IRA, the elimination of the catastrophic phase for patients and the lowering of out-of-pocket cost that that leveled the playing field, at least from a patient standpoint, between DPI and mebulizer. And so, there's still some differences between DPI and mebulize, between Part B and Part D in terms of out-of-pocket, whether a patient has supplemental insurance in Part B, et cetera, but I think what we feel comfortable saying is that to the extent that reimbursement was a barrier to starting a DPI, that will largely go away with the changes to the patient's out-of-pocket in Part So the out-of-pocket cost for a patient right now is, I think it's between around $3,000 to $3,500.

James Hart: We're really excited to with so many pathways and platforms in our organ transplantation business to have the neuro eval to surf in some ways as a pathfinder.

James Hart: As we bring more and more types of manufactured organs into the clinic or Mike do you want to chat on the IRA sure happy to so I think your question was with the changes to the IRA the elimination of the catastrophic catastrophic phase for patients and the lowering of.

Mike: Patient out of pocket costs does that level, the playing field from an O&M.

Mike: At least one patient standpoint.

Mike: DPI and nebulizer and so there's still some differences between between DPI and that'd be a lot between part D and part D. It comes without a pocket, whether a patient has supplemental insurance and part D et cetera, but I think what we feel comfortable saying is that to the extent that reimbursement was a barrier to starting a DPI.

Mike: That will largely go away with the changes too.

Mike: To the patient out of pocket and part D and we're actually starting to see the benefit of that and so just as a maybe a little bit of a quick background or for everybody the 5% out of pocket and the catastrophic phase goes away starting this year for.

Mike: For the patient so the out of pocket for a patient right now.

Mike: I think it's between around $3 $3500.

Michael Benkiewicz: And that covers all drugs. So that's not per drug; that's across all, for any medication they're on. So that's their out-of-pocket cost for this year.

Mike: And that covers all drug so that's just that's not prodrug that's across all and any any medications their arms. So that's their out of pocket for this year.

Michael Benkiewicz: That, you know, they have to spend that before Medicare kicks in in 2024. The nice thing about 2025 is that patients are able to spread that spending out over the 12 months, and that $3,500 drops to $2,000.

Mike: That they have to spend that before.

Mike: Medicare kicks in in 2024.

Mike: The nice thing about 2025 is that the patients are able to spread that spend out over the 12 months.

Mike: And that 3500 drops to 2000, and so lower about and they can spread it out over over 12 months. So yes, so because of all of those factors lower out of pocket.

Michael Benkiewicz: So lower them out, and they can spread it out over 12 months. So, you know, because of all of those factors, lower out-of-pocket, eventually, you'll be able to spread it out over 12 months, and it covers all of the drugs. I think what we're going to see is a reduction in the utilization of our patient assessment. And, in fact, we're already starting to see that.

Mike: Actually you'll be able to spread it out over 12 months.

Mike: All of the drugs I think what we're about what we're going to see is a reduction in utilization of our patient assistance program.

Mike: We're already starting to see that we had.

Michael Benkiewicz: We had a surprising number of patients that were able to switch over from patient assistance to commercial drugs in the first quarter. And I think once we get past the first quarter, because many of our patients are on multiple therapies, I think the vast majority of these patients will have spent their out-of-pocket limit by moving into the second quarter. And so, you know, we would expect that, as the year goes on, fewer and fewer patients will need to come into our patient assistance program, and therefore, our pap utilization will continue to decline over the balance of this year and then into 2020.

Mike: A surprising number of patients that were able to switch over.

Mike: For patient assistance to commercial drug in the first quarter and I think once we get past the first quarter.

Mike: Many of our patients are on multiple therapies I think the vast majority of these patients will have.

Mike: Spent their out of pocket limit it moving into the second quarter and so we would expect that.

Mike: As the year goes on fewer and fewer and fewer and fewer patients will need to come into our patient assistance program and therefore, our pap utilization will continue to decline over the balance of this year and into 2025, that's great. Mike. So again, we have been well prepared for it.

Michael Benkiewicz: That's great, Mike. So again, we have been well prepared for the IRA years ahead of time, and all that great groundwork and preparation is certainly paying off. Is there another question from the operator? Yes, the next question comes from Jessica Frye with JP Morgan. Please go ahead.

Mike: The IRR in years ahead of time and all of that great groundwork in preparation is certainly paying off.

Speaker Change: Is there a next question from the operator.

Speaker Change: Yes. The next question comes from Jessica Fye with Jpmorgan. Please go ahead.

Michael Benkiewicz: Hey guys, good morning. Thanks so much for taking my question. You mentioned Cetatarcept not coming to market in PHILD, and I know it's sort of tough to tell, but just given the investor questions we get about the pending competition in PAH, can you give us your latest thinking on the mix of Tybaso patients being treated for PAH versus PHILD and how that mix might evolve going forward as PHILD use continues to ramp? And then, if that mix is not answerable, can you elaborate on which of your troposomal products you see as perhaps least likely to see any disruption from Cetatarcept and why?

Jessica Fye: Guys. Good morning, Thanks, so much for taking my question.

Jessica Fye: You mentioned, the tighter sept coming not coming to market in ph ILD and I know, it's sort of tough to tell but just given the investor questions. We get about the pending competition in each can you give us your latest thinking on the mix of database of patients being treated for PHH versus ph ILD and how that.

Jessica Fye: Mix might evolve growing going forward is as ph ILD East continues to ramp and then if that mix is not answerable can you elaborate on which adhere to a profitable products you see as perhaps the least likely to see any disruption from the tighter stepped and why thank you.

Michael Benkiewicz: Thank you. Yeah, thanks, Jess. Good to hear your voice this morning. And Mike, we'll take your question. Sure. Thanks, Jess. Yes, I think in terms of a mix of PH and PHILD with type A.

Speaker Change: Yeah. Thanks, Jeff Good to hear your points are this morning and.

Mike will take your questions sure. Thanks, Josh Yes, so I think in terms of mix of.

Speaker Change: Ph in ph ILD with tiny so when.

Michael Benkiewicz: So, you know, we talked at your conference earlier this quarter, and we said that we believe it's around 50-50. And it's not a perfectly knowable answer just because of the way that the information comes in through the referral forms. But I think it's reasonable, and we feel, you know, pretty confident that it's in that 50-50 mix.

Mike: When we talked it.

At your conference or earlier this quarter et cetera, we believe is surround throughout 50 50.

Mike: That's not it's not perfectly knowable answer just because of the way that the information comes in through the referral forms, but I think it's reasonable and we feel.

Mike: Pretty pretty confident that's in it's in that 50 50 mix.

Michael Benkiewicz: And that should continue to increase in favor of PHILD as we continue to, you know, just get out and talk to prescribers. You know, we've talked about the fact that we expanded our sales force in the second half of last year. That process is complete. Those sales representatives are trained. They're out in the field.

Mike: That should continue it should it should continue to increase in favor of of ph ILD as we continue to just.

Mike: I'll talk to prescribers, we've talked about the fact that we expanded our sales force and the <unk>.

Mike: First half of last year.

That process is complete those sales representatives were trained and they're out in the field and so I think as we move into <unk>.

Michael Benkiewicz: And so, I think as we move into the rest of 2024, we'll start to realize the benefits of the greater share of voice in PHILD, those prescribers becoming more, I think, diligent and comfortable in screening patients and either referring them to PAH clinics or starting to treat those patients themselves with type A nebulizers or DPI. So, over time, I think we will continue to see PHILD as our big growth opportunity And that the next will trend in favor of PHILD as we move forward.

Mike: The rest of 2024, we will start to realize the benefits of the greater share of voice in ph ILD.

Mike: Those prescribers becoming more.

Mike: I think diligent and comfortable in screening patients in either referring them to PIH clinics are starting to treat treat those patients themselves with.

Mike: Tie ratio of annualized or a DPI. So so over time I think we continue to see ph ILD is a big growth opportunity in that mix will trend in favor of a ph ILD.

Mike: As we move forward.

Michael Benkiewicz: I think in terms of your question on the drugs, on which drug in PAH is least likely to be impacted, again, as I said, I have conviction that over the long term, really, there's not going to be much of an impact at all because all patients will need a process like that at some point. So really, I think it's a question of sequencing, and that's going to be kind of case dependent on the patient. But, you know, coming out of the gate, so to speak, I would say remodulants are probably the least likely to be impacted because patients that are on remodulin tend to be your more advanced patients, your more severe patients. It's a patient's either presenting with severe pulmonary hypertension.

Mike: I think in terms of the.

Mike: Your question on the drugs.

Mike: On which drug and PIH is least likely to be impacted.

Mike: Again as I said.

Mike: I have conviction that over the long term really theres not going to be much impact at all because all patients will need.

Mike: What's the cycle at some point, so really I think it's a question of sequencing and that's going to be dependent on the patient but.

Mike: Coming out of the gate so to speak that's I would say <unk> is probably the least likely to be impacted.

Mike: Because patients that are on one odd one tend to be a more advanced patients are more city locations and.

Mike: Thats, a patient's either presenting with.

Mike: Severe pulmonary hypertension.

Michael Benkiewicz: I think the vast, vast majority of physicians are gonna reach for remodulant first. And as I said in my opening remarks, there's really no evidence to suggest that patients are gonna be switched off of a process like that first to Patterson. Thanks, Mike. Great, great answers that provide a lot of insight. Thank you. Operator, next question, please. You have the next question comes from Joseph Baum with TD Cowan. Please go ahead. Hi there,

Mike: The vast vast majority of physicians are going to reach for module in first and as I said in my opening remarks.

Mike: There's really no evidence to suggest that patients the patients are going to be switched off of process likely first half or so.

Speaker Change: Thanks, Mike.

Mike: Great Great answers.

Five a lot of insight. Thank you operator next question. Please.

Mike: Yeah. The next question comes from Joseph <unk> with TD Cowen. Please go ahead.

Martine A. Rothblatt: Good morning. Thank you for taking my question and congratulations on the quarter. Maybe if you could tell us a little bit about how you expect to disclose some of the pivotal preclinical non-human primate data from the 10-gene transplantation program and maybe talk a little bit about the translatability from the experience in humans, performance could be a little bit better in humans or, I guess, in the community. Thank you. Yeah, thanks for the question.

Joseph: Hi, there good morning. Thank you for taking my question and congrats on the quarter.

If you could tell us a little bit about how you expect to disclose some of the pivotal preclinical nonhuman primate data from the Tianjin transplantation program, and maybe talk a little bit about the trampoline ability from.

Joseph: From the experience embedded into humans.

Joseph: Performance could be a little bit better than humans.

Speaker Change: Thank you.

Speaker Change: Yeah. Thanks for the question looking forward to speaking at your conference.

Martine A. Rothblatt: I am looking forward to speaking at your conference. You know, ordinarily, we at UT publish as much as we possibly can in the top journals in the field. And as soon as we have new scientific data available to share, like, for example, there is going to be a review article covering all of our genotransplantation activities in Physiological Reviews, which is a top five impact journal in the field, coming out in just a month or two. And that will answer, I think, you know, a great number of your questions in terms of the translatability of the data in the baboons, why the pig, why the 10 gene pig, and how all of this will extend into human development.

Speaker Change: Ordinarily we at UT we publish.

Speaker Change: Has as much as we possibly can in the.

Speaker Change: The top journals in the field.

Speaker Change: And.

Speaker Change: As soon as we have new scientific data available to share.

Speaker Change: For example.

Speaker Change: There is going to be a.

Speaker Change: Review article covering all of our casino transplantation activities in a physiological refuse which is like a top five impact journal in the field.

Speaker Change: Coming out in <unk>.

Speaker Change: And just a month or two.

Speaker Change: And that will answer I think you know a great number of your questions in terms of the translate ability of the data in the baboons.

Speaker Change: Why the pig wide the 10 gene pig and how all of this will extend into human development. So you'll be seeing that publication very shortly and like I said, it's a <unk>.

Martine A. Rothblatt: So you'll be seeing that publication very shortly. And like I said, it's a comprehensive review that includes a number of the leading experts in the field, as well as our top experts, such as Dr. Peterson. Beyond that, every time the FDA clears us to move to the next stage in clinical development, you know, we consider that an important thing to share, just like we shared in this call. The first time in the FDA's 100 or so years of history that they cleared a bioengineered organ for a human clinical trial was our mirror matrix at ELAP, and we shared that at the very next call afterwards. So, as the FDA shares guidance with us in terms of how to move our xenokidney and xenoharp into clinical trials, we'll positively share that with everybody in our FCC filings and on this call. And the exact protocols will, as I mentioned earlier, be asked that will, of course, be listed on clintrials.gov.

Speaker Change: Comprehensive review that concludes.

Speaker Change: <unk>, the leading experts in the field as well as our top experts such as Dr. Peterson.

Speaker Change: Beyond that.

Speaker Change: Every time, the FDA cleared us to move to the next stage in clinical development.

Speaker Change: We consider that an important thing to share just like we shared in this call. The first time in the fda's hundreds or so years history that they cleared a bioengineered organ to be into a human clinical trial.

Speaker Change: Our miro matrix Ie lap and we shared that.

Speaker Change: At the very next call afterwards, so as the FDA shares.

Speaker Change: Guidance with us in terms of how.

Speaker Change: Now to move ours, INO kidney and heart into the clinical trials will positively sure that with everybody in our SEC filings and on this call and the exact protocols will as I mentioned earlier too.

Speaker Change: That will of course be listed on a clean trials dot Gov.

Martine A. Rothblatt: Next question, operator. The next question comes from Hartaj Singh with Oppenheimer. Please go ahead. Great. Thank you. Good morning, everybody. Really nice quarter, Martine and team.

Speaker Change: Next question operator.

Speaker Change: The next question comes from hard Taj Singh with Oppenheimer. Please go ahead.

Hartaj Singh: Great. Thank you good morning, everybody, a really nice quarter.

Hartaj Singh: CN team.

Martine A. Rothblatt: And just keep going. You know, I've got a question slightly differently. Martine, you talked about enrolling the Relenopag studies by the end of this year and a pretty comprehensive pipeline that seems to be filling out even more and more. Can you just talk a little bit about the cadence of events, you know, from Relenopag and the other programs through this year and next year? Not looking for any guidance, but can you just the cadence of events for enrollment, you know, potential readouts, et cetera, you know, over the next essentially 12 to 24 months? Thank you.

And just keep it going you know I've got a question slightly differently.

Martin you talked about enrolling the <unk> studies by the end of this year.

Hartaj Singh: And a pretty comprehensive pipeline.

Hartaj Singh: That seems to be filling out even more and more.

Hartaj Singh: Can you just talk a little bit about the cadence of events former Lynda pack the other programs.

Hartaj Singh: Through this year next year not looking for any guidance, but can you just the cadence of events for enrollment potential.

Hartaj Singh: Potential readouts et cetera over the next essentially 12 months 24 months. Thank you.

Speaker Change: Thank you for that great question far ties and good to hear your voice this morning.

Dr. Lee Peterson: Thank you for that great question, Hartaj, and good to hear your voice this morning. I really like the question because, you know, a CEO probably shouldn't have favorites among their drugs any more than among their kids. But I would say that Lenapag is unbeatable, in my view, as an amazing medicine for somebody who has a family member with pulmonary hypertension. It's pretty much of a dream drug.

Speaker Change: We do like the question because.

Speaker Change: Our CEO, probably shouldnt have favorites among their drugs anymore than among their kids, but.

Speaker Change: I would say that the learner peg is unbeatable in my view has an amazing medicine.

Speaker Change: For somebody who has a family member with pulmonary hypertension, it's pretty much of a dream drug.

Martine A. Rothblatt: You know, subject to clinical trial outcomes, regulatory approval, and, you know, whatever is supposed to be put on the label. But in terms of dream characteristics, pills are best. I think everybody in the industry would agree with that. Secondly, once a day is better than two times a day or three times a day. I think everybody would agree with that. Third, titratability is better than not titratability. Everybody would agree with that.

Speaker Change: Subject to the clinical trial outcomes in our regulatory approval and whatever as opposed to be put on the label, but in terms of its the dream characteristics.

Speaker Change: So best I think everybody in the industry would agree with that.

Speaker Change: Secondly, once a day is better than two times, a day or three times a day I think everybody would agree with that.

Speaker Change: Third titrate ability is better than not titrated ability everybody would agree with that.

Martine A. Rothblatt: From a drug development standpoint, when you're following in on a pathway that's already been validated by the FDA, that reduces risk tremendously. And then what we have is a more potent member of that same pathway. So I think everything is in favor of Lenapag.

Speaker Change: From a drug development standpoint, when you're following in on a pathway that's already been validated by the FTA.

Speaker Change: That reduces risk tremendously and then what we have is a more potent member of that same pathway.

Speaker Change: I think everything is isn't.

Martine A. Rothblatt: And in terms of the specifics of your question, Hartaj, the time frame kind of expected events in terms of enrollment, readout, et cetera, during twenty four and twenty five. I'd like to turn the mic over to the head of the Relenapag program, our executive vice president for product development, Dr. Peterson. Fleet: Yeah, sure.

Speaker Change: Is in favor of a learner peg and in terms of the specifics of your question hard positive of a timeframe kind of expected events.

Speaker Change: In terms of enrollment readout et cetera during 'twenty four 'twenty five.

Speaker Change: To turn the.

Speaker Change: Mike over to the head of the relentless pegged program, our executive Vice President for business for product development, Dr. Peterson Lee.

Peterson Lee: Yeah sure. Thanks for the question and we're expecting to complete enrollment where I mean.

Dr. Lee Peterson: Thanks for the question. We're expecting to complete enrollment soon. We're, I mean, as you well know, this study is based on the accumulation of outcome events with regard to clinical worsening. And so, how the study is designed is that we complete enrollment, and then we follow the patients for a six month period until the pre-specified number of events are accumulated, which gives us the statistical significance to determine the difference between the active group and the placebo.

Speaker Change: Well no. This study is based on the accumulation of outcome events.

Peterson Lee: Regarding clinical worsening and so what how the study is designed is that we are we complete enrollment and then we follow the patients.

Peterson Lee: For the six month period for a standard follow up time frame as well as until the Prespecified number of events are accumulated which get the statistical significance to determine the difference between the active group and the placebo. So given all of that we are targeting.

Dr. Lee Peterson: So, given all of that, we are targeting enrollment to be completed this year, but really, the driver for study completion is the accumulation of the required number of events. Now, these patients are on. Most of them are on dual background therapy, and so we're tracking that very, very carefully as to the accumulation of these events. And again, we're targeting that our events will be accumulated as well as completion of the six-month follow-up period during 2025. Perfect.

Peterson Lee: Enrollment to be completed.

Peterson Lee: This year and but really the driver for the study.

Peterson Lee: Completion is accumulation of the required number of events now these patients are on.

Peterson Lee: Do go back most of them are unbilled background therapy.

And so we're tracking that very very carefully as to as to the accumulation of these events and again, where we're targeting that our events will be accumulated as well as completion of the six month follow up period during 2025.

Speaker Change: Perfect. Thank you so much Dr. Peterson, operator are there any more questions.

Martine A. Rothblatt: Thank you so much, Dr. Peterson. Operator, are there any more questions? Yes, one more question. Andreas Andretis with WebBush Securities. Please go ahead. Good morning, and thanks for squeezing our questions in here and congratulations on all the progress this quarter. I just have two from us here.

Speaker Change: One more question Andreas Andreadis with Wedbush Securities. Please go ahead.

Andreas Andreadis: Good morning, and thanks for squeezing our questions in here and congrats on all the progress this quarter.

Andreas Andreadis: Two from US here on the competitor front, how are you seeing safety playing a key role in adoption from new therapies.

Martine A. Rothblatt: On the competitor front, how are you seeing safety playing a key role in adoption for new therapies? And then also, you know, as we get closer to T-Time readouts, how are you thinking about the opportunity for type A, so an IPS, and where does it fit in the treatment landscape? And then just one more to squeeze in. You have quite a bit of cash. You were busy on the BD front last quarter.

Speaker Change: And then also.

Andreas Andreadis: Get closer to two time Readouts, how are you thinking about the opportunity for TV, and Ips and where it fits in the treatment landscape and then just one more to screen and then.

Andreas Andreadis: You have quite a bit of cash you are busy on the BD front last quarter. How are you thinking about business development opportunities and are you pursue going forward. Thanks, so much.

Martine A. Rothblatt: How are you thinking about business development opportunities in areas we should pursue going forward? Thanks so much. All righty, well, let's see, last and also the most questions. Okay, so we're going to have a kind of round table discussion about this, so we're going to go back to front. All capital allocation questions at United Therapeutics are under the management and guidance of our chief financial officer, James Edgeman, so I'm going to have him speak first. And then, with regard to competitive product positioning, Mike will have a few words to say. And finally, third and wrap-up hitter here, Dr. Peterson, if you could share some thoughts about, you know, monitoring safety aspects in clinical trials so that maybe you could share a little bit about the amazing job our clinical operations team does in terms of ensuring safety and our stellar pharmacovigilance and drug safety group. I think at United Therapeutics, safety is, I would say, our only priority. Nothing ever bumps the safety of safety.

Speaker Change: Alrighty, well, let's see.

Speaker Change: Last and also the most questions.

Speaker Change: Okay.

Speaker Change: We're gonna have all kind of a round table talking about here. So when you go back to front.

Speaker Change: Or are all capital allocation question since United Therapeutics are under the managed Smiths and guidance of our Chief Financial Officer, James Etch men, so I'm going to have.

James Christopher Edgemond: Him speak first and then with regard to the.

Speaker Change: The.

Speaker Change: The competitive product positioning.

James Christopher Edgemond: We'll have a few words to say and finally third and wrap up.

James Christopher Edgemond: Hitter here Dr. Peterson, if you could share some thoughts about monitoring safety aspects in clinical trials so that.

Dr. Peterson: Maybe you could share a little bit about the amazing job our clinical operations team does in terms of ensuring safety and our stellar pharmacovigilance and drug safety group.

Dr. Peterson: I think that at United Therapeutics Safety is I would say are only priority nothing ever bumps safety. So.

Martine A. Rothblatt: So James, can you speak about capital allocation? Yes, thank you, Martine. And Andreas, good to hear your voice this morning. I think you had two questions kind of weaving in. And I'll start with capital allocation and then corporate development. But our capital allocation priorities, Andreas, are still unchanged.

Speaker Change: James can you speak about the capital allocation.

James: Yes, Thank you Martijn and Andre it's good to hear your voice. This morning, I think you had two questions kind of weaved in.

James: And I'll start with capital allocation, and then corporate development, but our capital allocation priority. It's Andreas Theyre still unchanged, we have three priorities in order, which our internal research and development.

James Christopher Edgemond: We have three priorities in order, which are internal research and development, business and corporate development, and then Return of Capital to Shareholders. And we see ample opportunities to invest in ourselves and complementary businesses at this time. And at the J.P. Morgan Conference in January, Martine laid out the need to quickly access and deploy capital to support the potential commercial-scale build-out of DPS facilities, which could be several billions of dollars of CapEx over the next several years.

James: Business and corporate development, and then return of capital to shareholders and we see Apple on ample opportunities to invest in ourselves and complementary businesses at this time and at the Jpmorgan Conference in January Martijn laid out the need to quickly access and deploy capital to support the potential.

James: <unk> commercial scale build out of Dps facilities and this could be several billion billions of dollars of capex over the next several years and so there was a good discussion at the conference with respect to capital allocation and specifically looking at manufactured Oregon's now with respect to business and corporate development.

James Christopher Edgemond: And so there was a good discussion at the conference with respect to cap allocation and specifically looking at manufactured organs. Now, with respect to business and corporate development, we are constantly looking for potential acquisitions and also license opportunities. We tend to be most interested in complementary products and platforms that focus on rare lung and other cardiovascular diseases, but as you've also seen recently that we disclosed in the 10-K, we did a couple acquisitions, being IVIVA and MiroMatrix, that were focused on organ manufacturing. So, we're looking across the board and things that really complement the strengths of Unitharians internally and add to the research and development we're doing.

James: We are constantly looking for potential acquisitions and also in license opportunities.

James: We tend to be most interested in a complementary products and platforms that focus on rare lung and other cardiovascular diseases, but you've also seen recently that we disclosed in the 10-K.

James: We did a couple of acquisitions being I, Viva and mirror matrix there.

James: They were focused on Oregon manufacturing. So we're looking across the board and things that really complement the strengths of the unitary into internally and add to the research and development we're doing.

James Christopher Edgemond: So thank you for the question, and Martine, back to you. Yeah, I'm going to bounce it over to Mike to talk about the, you know, Thank you. Yes, it'll be okay. I think, Andres, your first question was leading to sort of safety questions with new therapies and how that..., how we think about that, and how that's typically handled. And, you know, really, I think it's a question as it relates to competitors. I think it's really a question for prescribers and for those manufacturers, to be honest. I think, you know, there is a safety profile that is presented as part of the clinical advocacy, and I think physicians have to kind of look at that as a way to balance the benefits and risks of that product relative to the patient's disease, other products that are available, and then, you know, as I said at the very beginning, it really kind of comes down to a case-dependent decision. So we'll just, you know, we'll just kind of see how that plays out over time.

Speaker Change: So thank you for the question Martijn back to you.

Speaker Change: Yeah, I'm going to bounce that over to Mike to talk about the.

Mike: Yes, okay.

Mike: I. Thank you for your first question was leading to sort of safety questions with new therapies and how that's.

Mike: How do we think about that how that's typically handle that in.

Mike: Really I think it's a question.

Mike: As it relates to competitors I think it's really a question for prescribers and for those manufacturers to be honest I think.

Mike: There is a safety profile, that's presented as part of the clinical efficacy and I think the physicians have to kind of look at that in a way the benefit risk.

Mike: Of that product.

Mike: Relative to the patient's disease other products that are available and then you know as I said at the very beginning it really kind of comes down to a case dependent decision. So we'll just we'll just kind of see how that plays out over overtime, great alrighty won't be I think you're off the hook because I think Mike commented enough on the safety question and operator.

Michael Benkiewicz: Great. All righty. Well, Lee, I think you're off the hook because I think Mike commented enough on the safety question.

Operator: And Operator, back to you. 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. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.

Speaker Change: Back to you.

Speaker Change: 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 Dot U N T.

Speaker Change: H E R Dot com.

Speaker Change: The conference has now concluded. Thank you for attending today's presentation you may now disconnect.

Speaker Change: Yes.