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What changed in UNITED THERAPEUTICS Corp's 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of UNITED THERAPEUTICS Corp's 2023 and 2024 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2024 report.

+537 added−529 removedSource: 10-K (2025-02-26) vs 10-K (2024-02-21)

Top changes in UNITED THERAPEUTICS Corp's 2024 10-K

537 paragraphs added · 529 removed · 420 edited across 9 sections

Item 1. Business

Business — how the company describes what it does

231 edited+56 added−84 removed297 unchanged
Biggest changeWe rely on Minnetronix Inc. and Phillips-Medisize Corp. to manufacture the nebulizer used in our Tyvaso Inhalation System and various third parties to manufacture the monthly disposable device accessories for the Tyvaso Inhalation System. We rely entirely on Lilly to manufacture Adcirca. We currently rely on third-party contract manufacturers to produce ralinepag.
Biggest changeWe currently rely entirely on MannKind to manufacture Tyvaso DPI finished drug product and inhalers, and we are constructing a facility in RTP to manufacture our own supply of Tyvaso DPI finished drug product and inhalers. 2024 Annual Report 17 We rely on Minnetronix Inc. and Phillips-Medisize Corp. to manufacture the nebulizer used in our Tyvaso Inhalation System and various third parties to manufacture the monthly disposable device accessories for the Tyvaso Inhalation System.
In March 2021, nebulized Tyvaso was approved to treat PH-ILD in addition to PAH. In May 2022, we also obtained FDA approval of Tyvaso DPI to treat both PAH and PH-ILD. We are engaged in further research and development of additional indications for Tyvaso DPI and nebulized Tyvaso to treat certain fibrotic lung conditions underlying PH-ILD.
In March 2021, nebulized Tyvaso was approved to treat PH-ILD in addition to PAH. In May 2022, we also obtained FDA approval of Tyvaso DPI to treat both PAH and PH-ILD. We are engaged in further research and development of additional indications for nebulized Tyvaso to treat certain fibrotic lung conditions underlying PH-ILD.
After participation in phase 2, 45 patients entered into an OLE study to further determine if ralinepag may be safe and effective for long-term use to treat patients with PAH. The study found that ralinepag had a manageable side effect profile, with a decrease in side effects for patients who continued taking ralinepag over time.
After participation in the phase 2 study, 45 patients entered into an OLE study to further determine if ralinepag may be safe and effective for long-term use to treat patients with PAH. The study found that ralinepag had a manageable side effect profile, with a decrease in side effects for patients who continued taking ralinepag over time.
Under our license agreement with Arena, we have an exclusive license to a variety of granted and pending patents and applications related to ralinepag covering drug formulation, manufacturing, and dosage, among others. Many of these patents and patent applications would be eligible for listing in the Orange Book. In March 2022, Arena was acquired by Pfizer Inc.
Under our license agreement with Arena, we have an exclusive license to a variety of granted and pending patents and patent applications related to ralinepag covering drug formulation, manufacturing, and dosage, among others. Many of these patents and patent applications would be eligible for listing in the Orange Book. In March 2022, Arena was acquired by Pfizer Inc.
Orphan Drugs Under the Orphan Drug Act, an applicant can request the FDA to designate a product as an “orphan drug” in the United States if the drug is intended to treat a rare disease or condition affecting fewer than 200,000 people in the United States, or for which there is no reasonable expectation that U.S. sales will be sufficient to recoup the development and production costs.
Orphan Drugs Under the Orphan Drug Act, an applicant can request that the FDA designate a product as an “orphan drug” in the United States if the drug is intended to treat a rare disease or condition affecting fewer than 200,000 people in the United States, or for which there is no reasonable expectation that U.S. sales will be sufficient to recoup the development and production costs.
We also plan to seek NADA approval for the pig lineage containing ten genetic modifications that we are using to generate our development-stage UHeart and UKidney products. In addition, production of xenografts intended for xenotransplantation must take place in DPF facilities that meet both cGMP requirements and unique requirements designed to ensure that our pigs are free of pathogens.
We also plan to seek NADA approval for the pig lineage containing ten genetic modifications that we are using to generate our development-stage UKidney and UHeart products. In addition, production of xenografts intended for xenotransplantation must take place in DPF facilities that meet both cGMP requirements and unique requirements designed to ensure that our pigs are free of pathogens.
Federal law requires that any company th at participates in the Medicaid Drug Rebate program also participate in the Public Health Service’s 340B drug pricing program, in order for federal funds to be available for the manufacturer’s drugs under Medicaid and Medicare Part B.
Federal law requires that any company th at participates in the Medicaid Drug Rebate program also participate in the Public Health Service’s 340B drug pricing program (the 340B program ), in order for federal funds to be available for the manufacturer’s drugs under Medicaid and Medicare Part B.
We are also focused on a variety of manufactured organ products with the goal of addressing the chronic shortage of transplantable organs for patients with end-stage organ diseases. Our principal executive offices are located at 1000 Spring Street, Silver Spring, Maryland 20910 and at 55 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709.
We are also focused on a variety of manufactured organ and organ alternative products with the goal of addressing the chronic shortage of transplantable organs for patients with end-stage organ diseases. Our principal executive offices are located at 1000 Spring Street, Silver Spring, Maryland 20910 and at 55 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709.
Miromatrix is also developing miroliver®, a fully-implantable manufactured liver product, and mirokidney®, a fully implantable manufactured kidney product, both of which are based on decellularized porcine organ scaffolds that have been reseeded with human-derived cells. Initially the Miromatrix products are intended to be allogeneic, requiring the use of standard immunosuppression protocols.
Miromatrix is also developing miroliver®, a fully implantable manufactured liver alternative product, and mirokidney®, a fully implantable manufactured kidney alternative product, both of which are based on decellularized porcine organ scaffolds that have been reseeded with human-derived cells. Initially the Miromatrix products are intended to be allogeneic, requiring the use of standard immunosuppression protocols.
In many cases, our manufactured organ products will involve seeking regulatory approval for categories of products that have never been approved by the FDA before, and therefore, our anticipated regulatory approach is subject to change as regulators issue new guidance, and as our discussions with the FDA and other agencies progress.
In many cases, our manufactured organ and organ alternative products will involve seeking regulatory approval for categories of products that have never been approved by the FDA before, and therefore, our anticipated regulatory approach is subject to change as regulators issue new guidance, and as our discussions with the FDA and other agencies progress.
Historically, these were the pumps primarily used to administer Remodulin to patients in the United States. In 2021, we launched the Remunity Pump to administer subcutaneous Remodulin, and in 2022 ICU Medical made an alternative pump, the CADD-Solis, available for intravenous Remodulin. We rely entirely on DEKA and its affiliates to manufacture the Remunity Pump for us.
Historically, these were the pumps primarily used to administer Remodulin to patients in the United States. In 2021, we launched the Remunity Pump to administer subcutaneous Remodulin, and in 2022 ICU Medical made an alternative pump, the CADD-Solis, available for intravenous Remodulin. We rely entirely on DEKA and its affiliates to manufacture the Remunity and RemunityPRO Pumps for us.
In 2010, the FDA granted orphan drug designation for Tyvaso, which resulted in an orphan exclusivity period that expired in July 2016. In March 2021, the FDA granted Tyvaso three-year clinical trial exclusivity for PH-ILD as a result of the INCREASE study and the expansion of the Tyvaso label to include a PH-ILD indication.
In 2010, the FDA granted orphan drug designation for Tyvaso, which resulted in an orphan exclusivity period that expired in July 2016. In March 2021, the FDA granted three-year clinical trial exclusivity for PH-ILD as a result of the INCREASE study and the expansion of the nebulized Tyvaso label to include a PH-ILD indication.
This allows therapeutic concentrations of Remodulin to be delivered at low flow rates via miniaturized infusion pumps for both subcutaneous and intravenous infusion. Remodulin can be continuously infused for up to 72 hours before refilling the external infusion pump, or up to 48 hours for diluted Remodulin.
This allows therapeutic concentrations of Remodulin to be delivered at low flow rates via infusion pumps for both subcutaneous and intravenous infusion. Remodulin can be continuously infused for up to 72 hours before refilling the external infusion pump, or up to 48 hours for diluted Remodulin.
EVLP technology increases the number of transplantable lungs by giving surgeons the ability to assess the function of marginal lungs to determine if the lungs are suitable for transplantation. This allows for the transplantation of lungs that would have otherwise not been transplanted.
EVLP technology increases the number of transplantable lungs by giving surgeons the ability to assess the function of lungs to determine if the lungs are suitable for transplantation. This allows for the transplantation of lungs that would have otherwise not been transplanted.
These studies using a preclinical human decedent model were conducted in brain-dead organ donors whose organs were determined to be ineligible for donation, with the consent of the donor’s family.
These studies using a preclinical human decedent model were conducted in brain-dead organ donors whose organs were determined to be ineligible for donation, with the consent of each donor’s family.
Any additional future changes to the definition of average manufacturer price and the Medicaid rebate amount could affect our 340B ceiling price calculations and negatively impact our results of operations.
Any future changes to the definition of average manufacturer price and the Medicaid rebate amount could affect our 340B ceiling price calculations and negatively impact our results of operations.
We feel strongly that such industry-leading productivity cannot be maintained without a core focus on our family of Unitherians, and a dedication to encouraging engagement, motivation, and focus on our goals and objectives. The Compensation Committee of our Board of Directors ( Board ) oversees our human capital management priorities, which are driven by the five key commitments noted above.
We believe strongly that such industry-leading productivity cannot be maintained without a core focus on our family of Unitherians, and a dedication to encouraging engagement, motivation, and focus on our goals and objectives. The Compensation Committee of our Board of Directors ( Board ) oversees our human capital management priorities, which are driven by the five key commitments noted above.
Our Miromatrix subsidiary is developing manufactured organs based on porcine scaffolds, but these products are not regulated as xenotransplantation products because they do not contain or require ex vivo contact with live cells, tissues, or organs from a nonhuman animal source. Miromatrix products contain human cells and are therefore subject to regulation as human cell- and tissue-based products.
Our Miromatrix subsidiary is developing manufactured organ alternatives based on porcine scaffolds, but these products are not regulated as xenotransplantation products because they do not contain or require ex vivo contact with live cells, tissues, or organs from a nonhuman animal source. Miromatrix products contain human cells and are therefore subject to regulation as human cell- and tissue-based products.
We maintain, at a minimum, a two-year inventory of nebulized Tyvaso, Remodulin, and Orenitram based on expected demand, and we contract with third-party contract manufacturers to supplement our capacity for some products, in order to mitigate the risk that we might not be able to manufacture internally sufficient quantities to meet patient demand.
We maintain, at a minimum, a two-year inventory of nebulized Tyvaso, Remodulin, and Orenitram based on expected demand, and we contract with third-party contract manufacturers to supplement our capacity for some products, to mitigate the risk that we might not be able to manufacture internally sufficient quantities to meet patient demand.
Item 1. Business Overview We build on the strength of our research and development expertise and a distinctive, entrepreneurial culture that encourages diversity, innovation, creativity, sustainability, and, simply, fun. Since inception, our mission has been to find a cure for pulmonary arterial hypertension ( PAH ) and other life-threatening diseases.
Item 1. Business Overview We build on the strength of our research and development expertise and a distinctive, entrepreneurial culture that encourages innovation, creativity, inclusion, sustainability, and, simply, fun. Since inception, our mission has been to find a cure for pulmonary arterial hypertension ( PAH ) and other life-threatening diseases.
Remodulin is stable at room temperature, so it does not need to be cooled during infusion and patients do not need to use cooling packs or refrigeration to keep it stable. Treprostinil is highly soluble under certain circumstances and highly potent, which enables us to manufacture Remodulin in concentrated solutions.
Remodulin is stable at room temperature, so it does not need to be cooled during infusion and patients do not need to use cooling packs or refrigeration to keep it stable. Treprostinil is highly soluble under certain conditions and highly potent, which enables us to manufacture Remodulin in concentrated solutions.
We have three unexpired patents related to the manufacture of treprostinil that expire in 2028 and are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book (see Orange Book below), for Tyvaso DPI, nebulized Tyvaso, Remodulin, and Orenitram.
We have two unexpired patents related to the manufacture of treprostinil that expire in 2028 and are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book (see Orange Book below), for Tyvaso DPI, nebulized Tyvaso, Remodulin, and Orenitram.
The regulatory safe harbors also are subject to regulatory revision and interpretation by a number of government agencies. Violations of the AKS are punishable by imprisonment, criminal fines, damages, civil monetary penalties, exclusion from participation in federal healthcare programs, and liability under the federal civil False Claims Act ( FCA ).
The regulatory safe harbors also are subject to regulatory revision and interpretation by government agencies. Violations of the AKS are punishable by imprisonment, criminal fines, damages, civil monetary penalties, exclusion from participation in federal healthcare programs, and liability under the federal civil False Claims Act ( FCA ).
We have been granted two U.S. patents directed to a method of treating pulmonary hypertension and a kit for treating pulmonary hypertension. These two patents expire in 2028 and are listed in the Orange Book. We have also been granted two patents on methods of treating pulmonary hypertension by administering treprostinil by inhalation, which expire in 2027.
We have been granted two U.S. patents directed to a method of treating pulmonary hypertension and a kit for treating pulmonary hypertension. These two patents expire in 2028 and are listed in the Orange Book. We have also been granted a patent on methods of treating pulmonary hypertension by administering treprostinil by inhalation, which expires in 2027.
Toward this goal we have successfully obtained approval from the U.S. Food and Drug Administration ( FDA ) for several medicines, we are always conducting new clinical trials, and we are working to create an unlimited supply of manufactured organs for transplantation.
Toward this goal, we have successfully obtained approval from the U.S. Food and Drug Administration ( FDA ) for several medicines, we are always conducting new clinical trials, and we are working to create an unlimited supply of manufactured organs and organ alternatives for transplantation.
In June 2023, Liquidia announced it had entered into an exclusive licensing agreement for development and commercialization of L606 in North America, and that the product is the subject of a phase 3 clinical trial in patients with PH-ILD, with the intent of obtaining approval for the treatment of both PAH and PH-ILD via the 505(b)(2) regulatory pathway, with nebulized Tyvaso as the reference listed drug.
In June 2023, Liquidia announced it had entered into an exclusive licensing agreement with Pharmosa for development and commercialization of L606 in North America, and that the product is the subject of an upcoming phase 3 clinical trial in patients with PH-ILD, with the intent of obtaining approval for the treatment of both PAH and PH-ILD via the 505(b)(2) regulatory pathway, with nebulized Tyvaso as the reference listed drug.
The lung scaffold used in the ULung is printed using 3-D printers being developed in collaboration with 3D Systems, Inc. Our Organ Manufacturing Group located in Manchester, New Hampshire, has achieved recognition for developing the world’s most complex 3-D printed object.
The lung scaffold used in the ULung is printed using 3D printers being developed in collaboration with 3D Systems, Inc. Our Organ Manufacturing Group, located in Manchester, New Hampshire, has achieved recognition for developing the world’s most complex 3D printed object.
See Governmental Regulation—Patent Term and Regulatory Exclusivity below for further details. Tyvaso DPI currently has eight unexpired Orange Book-listed patents with expiration dates ranging from 2025 to 2042. Nebulized Tyvaso currently has eight unexpired Orange Book-listed patents expiring at various dates from 2027 to 2042.
See Governmental Regulation—Patent Term and Regulatory Exclusivity below for further details. Tyvaso DPI currently has six unexpired Orange Book-listed patents with expiration dates ranging from 2025 to 2042. Nebulized Tyvaso currently has six unexpired Orange Book-listed patents expiring at various dates from 2027 to 2042.
The 21st Century Cures Act sets forth a number of provisions pertaining to combination products, such as procedures for negotiating disagreements between sponsors and the FDA and requirements intended to streamline FDA premarket reviews of combination products that contain an already-approved component.
The 21st Century Cures Act sets forth provisions pertaining to combination products, such as procedures for negotiating disagreements between sponsors and the FDA and requirements intended to streamline FDA premarket reviews of combination products that contain an already-approved component.
Our people mission focuses on five key commitments, providing Unitherians with: • Challenging, innovative work • Opportunities for career advancement • Autonomy to do their best work • Inspiring work environment allowing for work/life integration • Competitive pay and benefits In 2023, we achieved approximately $2.0 million in revenue per employee, which ranks near the top of our industry peer group.
Our people mission focuses on five key commitments, providing Unitherians with: • Challenging, innovative work • Opportunities for career advancement • Autonomy to do their best work • Inspiring work environment allowing for work/life integration • Competitive pay and benefits In 2024, we achieved approximately $2.2 million in revenue per employee, which ranks near the top of our industry peer group.
Environmental Matters We are subject to a number of laws and regulations that require compliance with federal, state, and local regulations for the protection of the environment. We believe that our operations comply in all material respects with such applicable laws and regulations.
Environmental Matters We are subject to laws and regulations that require compliance with federal, state, and local regulations for the protection of the environment. We believe that our operations comply in all material respects with such applicable laws and regulations.
Furthermore, the 21st Century Cures Act applies exclusivity provisions (e.g., new chemical entity and orphan drug exclusivities) to the device clearance and approval process for combination products with a device primary mode of action. Organ Manufacturing Our organ manufacturing programs present unique regulatory challenges, relative to our more traditional drugs and biologic products.
Furthermore, the 21st Century Cures Act applies exclusivity provisions (e.g., new chemical entity and orphan drug exclusivities) to the device clearance and approval process for combination products with a device primary mode of action. Organ Manufacturing and Organ Alternatives Our manufactured organ and organ alternative programs present unique regulatory challenges, relative to our more traditional drugs and biologic products.
These data points, combined with substantial preclinical evidence of antifibrotic activity of treprostinil, suggest that nebulized Tyvaso may offer a treatment option for patients with IPF. We believe there are approximately 100,000 IPF patients in the United States. The TETON PPF study was also prompted by data from the INCREASE study.
These data points, combined with substantial preclinical evidence of antifibrotic activity of treprostinil, suggest that nebulized Tyvaso may offer a treatment option for patients with IPF. We believe there are approximately 100,000 IPF patients in the United States. The TETON PPF study was also prompted by a post-hoc analysis of data from the INCREASE study.
While these projects will be capital intensive, the timing and volume of these expenditures will be staggered and paced in a manner intended to balance our need to address market demand as soon as possible following launch with the need to defer the most significant capital expenditures until we achieve certain clinical trial milestones.
While these projects will be capital-intensive, the timing and volume of these expenditures will be staggered and paced in a manner intended to balance our need to address market demand as soon as possible following FDA approval with the need to defer the most significant capital expenditures until we achieve certain clinical trial milestones.
T hese distributors are required to maintain certain minimum inventory levels in order to ensure an uninterrupted supply to patients who are prescribed our therapies. We compensate Accredo and CVS Specialty on a fee-for-service basis for certain ancillary services in connection with the distribution of these products.
T hese distributors are required to maintain certain minimum inventory levels to facilitate an uninterrupted supply to patients who are prescribed our therapies. We compensate Accredo and CVS Specialty on a fee-for-service basis for certain ancillary services in connection with the distribution of these products.
Following the successful INCREASE study of nebulized Tyvaso in patients with PH-ILD, including patients with underlying idiopathic pulmonary fibrosis ( IPF ) and combined pulmonary fibrosis and emphysema, the FDA approved our efficacy supplement to the nebulized Tyvaso NDA in March 2021. As a result, nebulized Tyvaso’s label was updated to include the PH-ILD indication.
Following the successful INCREASE study of nebulized Tyvaso in patients with PH-ILD, including patients with underlying idiopathic pulmonary fibrosis ( IPF ) and combined pulmonary fibrosis and emphysema, the FDA approved our efficacy supplement to the nebulized Tyvaso New Drug Application ( NDA ) in March 2021. As a result, nebulized Tyvaso’s label was updated to include the PH-ILD indication.
With advances in technology, we believe that creating an unlimited supply of tolerable manufactured organs is now principally an engineering challenge, and we are dedicated to finding engineering solutions.
With advances in technology, we believe that creating an unlimited supply of tolerable manufactured organs and organ alternatives is now principally an engineering challenge, and we are dedicated to finding engineering solutions.
Similarly, there are a number of legislative proposals in the United States, at both the federal and state level, that could impose new obligations or limitations in areas affecting our business. These laws and regulations are evolving and subject to interpretation, and may impose limitations on our activities or otherwise adversely affect our business.
Similarly, there are legislative proposals in the United States, at both the federal and state level, that could impose new obligations or limitations in areas affecting our business. These laws and regulations are evolving and subject to interpretation, and may impose limitations on our activities or otherwise adversely affect our business.
Because Unitherians are key to driving our strategic goals, we provide robust people programs that demonstrate the high value we place on the financial, mental, and physical wellness of Unitherians.
Because Unitherians are key to driving our strategic goals, we provide robust people programs that demonstrate the high value we place on the financial, mental, and physical wellbeing of Unitherians.
Mahon, J.D. 60 Executive Vice President, General Counsel, and Corporate Secretary Martine Rothblatt, Ph.D., J.D., M.B.A . , founded United Therapeutics in 1996 and has served as Chairperson and Chief Executive Officer since its inception. Previously, she created the satellite radio company SiriusXM. She is an inventor or co‑inventor on nine U.S. patents, with additional patents pending.
Mahon, J.D. 61 Executive Vice President, General Counsel, and Corporate Secretary Martine Rothblatt, Ph.D., J.D., M.B.A . , founded United Therapeutics in 1996 and has served as Chairperson and Chief Executive Officer since its inception. Previously, she created the satellite radio company SiriusXM. She is an inventor or co‑inventor on ten U.S. patents, with additional patents pending.
These data include the average manufacturer price and, in the case of innovator products, the best price for each drug which, in general, represents the lowest price available from the manufacturer to any entity in the U.S. in any pricing structure, calculated to include all applicable sales and associated rebates, discounts, and other price concessions.
These data include the average manufacturer price and, in the case of innovator products, the best price for each drug which, in general, represents the lowest price available from the manufacturer to certain entities in the U.S. in any pricing structure, calculated to include all applicable sales and associated rebates, discounts, and other price concessions.
The IRA permits the Secretary of the Department of Health and Human Services ( HHS ) to implement many of these provisions through guidance, as opposed to regulation, for the initial years. HHS has issued guidance, and is expected to continue to issue guidance, even while lawsuits challenging the IRA remain pending.
The IRA permits the Secretary of the Department of Health and Human Services ( HHS ) to implement many of these provisions through guidance, as opposed to regulation, for the initial years. HHS has issued guidance, and is expected to continue to issue guidance, even while multiple lawsuits challenging the IRA negotiation requirement remain pending.
We cannot assure you that any submissions we are required to make under the Medicaid Drug Rebate program, the 340B program, the VA/FSS program, the Tricare Retail Pharmacy Program, and other governmental drug pricing programs will not be found to be incomplete or incorrect.
We cannot assure you that any submissions we are required to make under the Medicaid Drug Rebate program, Medicare Part B, the 340B program, the VA/FSS program, the Tricare Retail Pharmacy Program, and other governmental drug pricing programs will not be found to be incomplete or incorrect.
In June and July 2022, NYU surgeons tested two UHearts from our genetically modified pigs in brain-dead organ donors maintained on artificial support. In each case, normal function was observed for our UHearts over a three-day study period, without signs of early rejection. The results were published in Nature Medicine in July 2023.
In June and July 2022, NYU surgeons tested two UHearts from our gene-edited pigs in brain-dead organ donors maintained on artificial support. In each case, normal function was observed for our UHearts over a three-day study period, without signs of early rejection. The results were published in Nature Medicine in July 2023.
The FDA’s compassionate use regulations allow a physician to apply to use an unapproved product outside of a clinical trial to treat an individual patient with a serious or immediately life-threatening disease or condition when no satisfactory alternative therapy is available. The first patient, transplanted in January 2022, survived for approximately two months with the UHeart.
The FDA’s compassionate use regulations allow a physician to apply to use an unapproved product outside of a clinical trial to treat an individual patient with a serious or immediately life-threatening disease or condition when no satisfactory alternative therapy is available. The first patient, who received a xenotransplant in January 2022, survived for approximately two months with the UHeart.
In June 2023, our third-party contract manufacturer, Gilero, obtained FDA clearance for a cartridge to be used with the MS-3 pump for subcutaneous infusion of Remodulin. This clearance will enable us to help ensure continuity of cartridge supplies to existing patients using the MS-3 pump. We are also engaged in further efforts to develop alternative pumps to administer Remodulin.
In June 2023, our third-party contract manufacturer obtained FDA clearance for a cartridge to be used with the MS-3 pump for subcutaneous infusion of Remodulin. This clearance enables us to help ensure continuity of cartridge supplies to existing patients using the MS-3 pump. We are also engaged in further efforts to develop alternative pumps to administer Remodulin.
Nebulized Tyvaso and Orenitram—Potential Future Generic Competition We settled litigation with Watson and Actavis related to their ANDAs seeking FDA approval to market generic versions of nebulized Tyvaso and Orenitram, respectively, before the expiration of certain of our U.S. patents.
Nebulized Tyvaso and Orenitram—Potential Future Generic Competition We settled litigation with Watson Laboratories, Inc. ( Watson ) and Actavis Laboratories FL, Inc. ( Actavis ) related to their ANDAs seeking FDA approval to market generic versions of nebulized Tyvaso and Orenitram, respectively, before the expiration of certain of our U.S. patents.
Because these products use cell- and tissue-based components, we anticipate that Miromatrix products will be required to be manufactured in accordance with both cGTP and cGMP standards. We believe our 3-D printed, regenerative medicine, and bio-artificial organ products will be subject to similar regulatory requirements as the Miromatrix products, and will necessitate BLA approvals in the U.S.
Because these products use cell- and tissue-based components, we anticipate that Miromatrix products will be required to be manufactured in accordance with both cGTP and cGMP standards. We believe our 3D printed, regenerative medicine, and bio-artificial organ alternative products will be subject to similar regulatory requirements as the Miromatrix products, and will necessitate BLA approvals in the U.S.
We have a policy that prohibits all forms of unlawful harassment and retaliation and provide training to all Unitherians on their responsibilities and protections under this policy. 2023 Annual Report 33 PBC Conversion. In 2021, we converted United Therapeutics into a public benefit corporation, becoming the first company in our industry to do so.
We have a policy that prohibits all forms of unlawful harassment and retaliation and provide training to all Unitherians on their responsibilities and protections under this policy. PBC Conversion. In 2021, we converted United Therapeutics into a public benefit corporation, becoming the first company in our industry to do so.
This profile contrasts favorably with non-treprostinil based, continuously-infused prostacyclin therapies on the market: Flolan ® ; Veletri ® ; and generic epoprostenol. 2023 Annual Report 5 Flolan and generic epoprostenol are not stable at room temperature (and therefore require refrigeration or the use of cooling packs), but Veletri may be stable at room temperature depending on its concentration.
This profile contrasts favorably with non-treprostinil based, continuously infused prostacyclin therapies on the market: Flolan ® ; Veletri ® ; and generic epoprostenol. Flolan and generic epoprostenol are not stable at room temperature (and therefore require refrigeration or the use of cooling packs), but Veletri may be stable at room temperature depending on its concentration.
Meat from GalSafe pigs is currently being produced for individuals with alpha-gal syndrome, an allergy to meat caused by a bite from the lone star tick. This approval marked only the second FDA approval of a genetically modified animal as a source of food, and the first such approval for a mammal.
Meat from GalSafe pigs is currently being produced for individuals with alpha-gal syndrome, an allergy to meat caused by a bite from the lone star tick. This approval marked only the second FDA approval of a gene-edited animal as a source of food, and the first such approval for a mammal.
We will pay MannKind up to $40.0 million in additional option exercise and development milestone payments 2023 Annual Report 17 for each product (if any) added to the license pursuant to this option, as well as a low double-digit royalty on our net sales of any such product.
We will pay MannKind up to $40.0 million in additional option exercise and development milestone payments for each product (if any) added to the license pursuant to this option, as well as a low double-digit royalty on our net sales of any such product.
The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order, or use of medicinal products, which is prohibited in the EU, is governed by the national anti-bribery laws of the 2023 Annual Report 31 EU member states. Violation of these laws could result in substantial fines and imprisonment.
The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order, or use of medicinal products, which is prohibited in the EU, is governed by the national anti-bribery laws of the EU member states. Violation of these laws could result in substantial fines and imprisonment.
We are enrolling ADVANCE OUTCOMES , which is a phase 3, event-driven study of ralinepag in PAH patients with a primary endpoint of time to first clinical worsening event. ADVANCE OUTCOMES is a global, multi-center, placebo-controlled trial that includes patients on approved oral background PAH therapies.
We are enrolling ADVANCE OUTCOMES , which is a phase 3, event-driven study of an extended-release formulation of ralinepag in PAH patients with a primary endpoint of time to first clinical worsening event. ADVANCE OUTCOMES is a global, multi-center, placebo-controlled trial that includes patients on approved oral background PAH therapies.
Cybersecurity and data security threats continue to evolve and raise the risk of an incident that could affect our operations or compromise our business information or sensitive personal information, including health data. We may also need to collect more extensive health-related information from our employees to manage our workforce.
Cybersecurity and data security threats continue to evolve and raise the risk of an incident that could affect our operations or compromise our business information or sensitive personal information, including health data. 2024 Annual Report 31 We may also need to collect more extensive health-related information from our employees to manage our workforce.
Our CLES EVLP service utilizes an acellular organ perfusate (STEEN™ solution) that is regulated by the FDA as a medical device. As such, we plan to submit a PMA to the FDA for approval of the CLES technology.
Our CLES EVLP service utilizes an acellular organ perfusate (STEEN™ solution) that is regulated by the FDA as a medical device. As such, we submitted a PMA to the FDA for approval of the CLES technology.
Hoffman-La Roche Ltd. ( Roche ). In addition, Ofev is the only therapy approved to treat PPF. However, clinical studies have indicated that these therapies only slow lung function decline in IPF (and in the case of Ofev, PPF) patients, resulting in a significant unmet need for therapies that halt or reverse lung function decline in IPF and PPF.
In addition, Ofev is the only therapy approved to treat PPF. However, clinical studies have indicated that these therapies only slow lung function decline in IPF (and in the case of Ofev, PPF) patients, resulting in a significant unmet need for therapies that halt or reverse lung function decline in IPF and PPF.
For example, our xenotransplantation products will be regulated by the FDA’s Center for Biologics Evaluation and Research ( CBER ) as biologics. However, modifications to the genome of pigs are subject to a separate FDA approval process as new animal drugs, which falls within the purview of the FDA’s Center for Veterinary Medicine.
For example, our xenotransplantation products are regulated by the FDA’s Center for Biologics Evaluation and Research ( CBER ) as biologics. However, edits to the genome of pigs are subject to a separate FDA approval process as new animal drugs, which falls within the purview of the FDA’s Center for Veterinary Medicine.
We are engaged in research and development of a variety of technologies designed to increase the supply of transplantable organs and tissues and to improve outcomes for transplant recipients through xenotransplantation, regenerative medicine, 3-D organ bioprinting, bio-artificial organs, and ex vivo lung perfusion.
We are engaged in research and development of a variety of technologies designed to increase the supply of transplantable organs and tissues and to improve outcomes for transplant recipients through xenotransplantation, regenerative medicine, 3D bioprinting of organ alternatives, bio-artificial organ alternatives, and ex vivo lung perfusion.
Our patent portfolio covers various aspects of our organ manufacturing programs, including genetic constructs, manufacturing methods, end products, and components used in the manufacture of organs. The applicability of our patent portfolio to our programs will depend on the final commercial organ manufacturing products we provide and processes we use and the timing of regulatory approvals.
Our patent portfolio covers various aspects of our manufactured organ and organ alternative programs, including genetic constructs, manufacturing methods, end products, and components used in the manufacture of these products. The applicability of our patent portfolio to our programs will depend on the final commercial organ manufacturing products we provide and processes we use and the timing of regulatory approvals.
Other potential consequences include: (1) restrictions on the marketing or manufacturing of the product; (2) fines, warning letters, or holds on post-approval clinical trials; (3) refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product license approvals; (4) product seizure or detention, or refusal to permit the import or export of products; or (5) injunctions or the imposition of civil or criminal penalties.
Other potential consequences include: restrictions on the marketing or manufacturing of the product; fines, warning letters, or holds on post-approval clinical trials; refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product license approvals; product seizure or detention, or refusal to permit the import or export of products; or injunctions or the imposition of civil or criminal penalties.
Its lung scaffold designs consist of a record 44 trillion voxels that lay out 4,000 kilometers of pulmonary capillaries and 200 million alveoli, which demonstrate gas exchange in preclinical models. Under our agreement with 3D Systems, we also have the exclusive right to develop additional human solid organs using 3D Systems’ printing technology. • Miromatrix Medical .
Its lung scaffold designs consist of a record 44 trillion voxels that lay out 4,000 kilometers of pulmonary capillaries and 200 million alveoli, which demonstrate gas exchange in preclinical models. Under our agreement with 3D Systems, we also have the exclusive right to develop additional human solid organ alternatives using 3D Systems’ printing technology. • IVIVA .
We believe that this new inhaled treprostinil therapy provides substantial lifestyle benefits to PAH and PH-ILD patients, as compared with nebulized Tyvaso therapy, because it is: (1) less time-consuming to administer and easier to maintain, as the device is provided in pre-filled, single-use, disposable cassettes, eliminating the need for cleaning and filling; and (2) mobile and more convenient, as the compact design of the inhaler and drug cassettes used with Tyvaso DPI enables the device to easily fit into the patient’s pocket and the device does not require electricity to function.
We believe that Tyvaso DPI provides substantial lifestyle benefits to PAH and PH-ILD patients, as compared with nebulized Tyvaso therapy, because it is: (1) less time-consuming to administer and easier to maintain, as the device is provided in pre-filled, single-use, multiple-strength, disposable cartridges, eliminating the need for cleaning and filling; and (2) mobile and more convenient, as the compact design of the inhaler and drug cartridges used with Tyvaso DPI enables the device to easily fit into the patient’s pocket and the device does not require electricity to function.
Because tissues from pigs containing this modification do not contain detectable levels of the alpha-gal sugar, we refer to materials derived from this pig as GalSafe®. In December 2020, the GalSafe pig was approved by the FDA for use as human food or as a potential source for biomedical purposes.
Because tissues from pigs containing this gene edit do not contain detectable levels of the alpha-gal sugar, we refer to materials derived from this pig as GalSafe®. In December 2020, the GalSafe pig was approved by the FDA for use as human food and as a potential source for biomedical purposes.
Although there are a number of statutory exceptions and regulatory safe harbors to the AKS protecting certain common business arrangements and activities from prosecution or regulatory sanctions, the exceptions and safe harbors are drawn narrowly.
Although there are statutory exceptions and regulatory safe harbors to the AKS protecting certain common business arrangements and activities from prosecution or regulatory sanctions, the exceptions and safe harbors are drawn narrowly.
( Smiths Medical , which was acquired by ICU Medical, Inc., or ICU Medical ) manufactured the pumps used by most patients in the United States to administer Remodulin, including the CADD-MS ® 3 ( MS-3 ) pump used to deliver subcutaneous Remodulin, and the CADD-Legacy ® pump to deliver intravenous Remodulin.
( Smiths Medical , which was acquired by ICU Medical, Inc., or ICU Medical ) manufactured the pumps used by most patients in the United States to administer Remodulin, including the CADD-MS ® 3 ( MS-3 ) pump used to deliver subcutaneous Remodulin, 2024 Annual Report 5 and the CADD-Legacy ® pump to deliver intravenous Remodulin.
Remodulin currently has ten unexpired Orange Book-listed patents with expiration dates ranging from 2024 to 2029. Orenitram currently has twelve unexpired Orange Book listed patents with expiration dates ranging from 2024 to 2031. Additional patent applications are pending, and if granted, may be eligible for listing in the Orange Book. Regulatory Exclusivity • Tyvaso DPI and Nebulized Tyvaso.
Remodulin currently has five unexpired Orange Book-listed patents with expiration dates ranging from 2028 to 2029. Orenitram currently has twelve unexpired Orange Book listed patents with expiration dates ranging from 2026 to 2031. Additional patent applications are pending, and if granted, may be eligible for listing in the Orange Book. Regulatory Exclusivity • Tyvaso DPI and Nebulized Tyvaso.
Current therapies approved by the FDA for PAH focus on three distinct molecular pathways: the prostacyclin pathway, the nitric oxide pathway, and the endothelin pathway. The classes of drugs that target these three pathways are: • Prostacyclin Analogues and IP Prostacyclin Receptor Agonists.
Current therapies approved by the FDA for PAH focus on four distinct molecular pathways: the prostacyclin pathway, the nitric oxide pathway, the endothelin pathway, and activin signaling pathway. The classes of drugs that target these pathways are: • Prostacyclin Analogues and IP Prostacyclin Receptor Agonists.
The inventory of MS-3 pu mps held by specialty pharmacy distributors (including the additional pumps we funded the manufacture of) is now exhausted. In June 2023, our third-party contract manufacturer, Gilero, LLC ( Gilero ), obtained FDA clearance for a cartridge to be used with the MS-3 pump for subcutaneous infusion of Remodulin.
The inventory of MS-3 pu mps held by specialty pharmacy distributors (including the additional pumps we funded the manufacture of) is now exhausted. In June 2023, our third-party contract manufacturer, Gilero LLC, which was recently acquired by Sanner GmbH, obtained FDA clearance for a cartridge to be used with the MS-3 pump for subcutaneous infusion of Remodulin.
The ULung is a development-stage engineered lung composed of a 3-D printed lung scaffold cellularized with either allogeneic human lung cells, or the patient’s own cells (known as “autologous” cells), with the goal of reducing or eliminating the need for immunosuppression.
The ULung is a development-stage engineered lung alternative composed of a 3D printed lung scaffold cellularized with either allogeneic human lung cells, or the patient’s own cells (known as “autologous” cells) with the goal of reducing or eliminating the need for immunosuppression.
Additionally, our license agreement 2023 Annual Report 13 with MannKind includes rights to a substantial portfolio of additional issued U.S. patents related to a component of the drug product and methods of making the drug product, which expire at various dates through 2035, and pending applications that, if issued, could extend protection to 2042 or beyond. • Nebulized Tyvaso.
Additionally, our license agreement with MannKind includes rights to a substantial portfolio of additional issued U.S. patents related to a component of the drug product and methods of making the drug product, which expire at various dates through 2035, and pending applications that, if issued, could provide protection to 2042 or beyond. • Nebulized Tyvaso.
The UThymoKidney™ is a development-stage kidney from a pig with a single genetic modification, together with tissue from the pig’s thymus. The pig’s thymus tissue is intended to condition the recipient’s immune system to recognize the UThymoKidney as “self” and reduce the likelihood of rejection.
The UThymoKidney™ is a development-stage kidney from a pig with a single gene edit, together with tissue from the pig’s thymus. The pig’s thymus tissue is intended to condition the recipient’s immune system to recognize the UThymoKidney as “self” and reduce the likelihood of rejection.
In 2023, Johnson & Johnson reported global sales of Uptravi of nearly $1.6 billion, including over $1.3 billion in U.S. sales, reflecting a growth rate of approximately 20% over 2022. Organ Manufacturing Each year, end-stage organ failure kills millions of people. A significant number of these patients could have benefited from an organ transplant.
In 2023, Johnson & Johnson reported global sales of Uptravi of nearly $1.6 billion, including over $1.3 billion in U.S. sales, reflecting a growth rate of approximately 20 percent over 2022. Manufactured Organs and Organ Alternatives Each year, end-stage organ failure kills millions of people. A significant number of these patients could have benefited from an organ transplant.
Tyvaso DPI is a drug-device combination product that incorporates the dry powder formulation technology and Dreamboat ® inhalation device technology used in MannKind’s Afrezza ® (insulin human) Inhalation Powder product which was approved by the FDA in 2014 to treat patients with diabetes.
Tyvaso DPI is a drug-device combination product that incorporates the dry powder formulation technology and Dreamboat ® inhalation device technology used in MannKind’s Afrezza ® (insulin human) Inhalation Powder product, which was approved by the FDA in 2014 to treat patients with diabetes. Tyvaso DPI is administered four times per day.
In particular, the preliminary results showed that Orenitram, when taken with an oral PAH background therapy, decreased the risk of a clinical worsening event versus 6 United Therapeutics, a public benefit corporation placebo by 25 percent (p=0.0391), driven by a 61 percent decrease in the risk of disease progression for patients taking Orenitram, when compared to placebo (p=0.0002).
In particular, the preliminary results showed that Orenitram, when taken with an oral PAH background therapy, decreased the risk of a clinical worsening event versus placebo by 25 percent (p=0.0391), driven by a 61 percent decrease in the risk of disease progression for patients taking Orenitram, when compared to placebo (p=0.0002).
The single gene that is inactivated in the pig is responsible for the synthesis of alpha-gal, a sugar on the surface of cells that can cause the immediate rejection of an organ when transplanted into the human body.
The single gene that is disrupted in the pig is responsible for the synthesis of alpha-gal, a sugar on the surface of cells that can cause immediate rejection of a porcine organ when transplanted into the human body.
We recognized $359.4 million, $325.1 million, and $306.1 million in Orenitram net product sales, representing 15 percent, 17 percent, and 18 percent of our total revenues for the years ended December 31, 2023, 2022, and 2021, respectively. In 2013, the FDA approved Orenitram for the treatment of PAH patients to improve exercise capacity.
We recognized $434.3 million, $359.4 million, and $325.1 million in Orenitram net product sales, representing 15 percent, 15 percent, and 17 percent of our total revenues for the years ended December 31, 2024, 2023, and 2022, respectively. In 2013, the FDA approved Orenitram for the treatment of PAH patients to improve exercise capacity.
Tyvaso DPI, Nebulized Tyvaso, Remodulin, and Orenitram Proprietary Rights We have a number of issued patents and pending patent applications covering our treprostinil-based products, Tyvaso DPI, nebulized Tyvaso, Remodulin, and Orenitram.
Tyvaso DPI, Nebulized Tyvaso, Remodulin, and Orenitram Proprietary Rights We have issued patents and pending patent applications covering our treprostinil-based products, Tyvaso DPI, nebulized Tyvaso, Remodulin, and Orenitram.
Failure to comply with the applicable federal or state requirements could result in, among other things: (1) fines, injunctions, and civil penalties; (2) recall or seizure of products; (3) operating restrictions, partial suspension, or total shutdown of manufacturing; (4) refusing requests for approval of new products; (5) withdrawing approvals already granted; and (6) criminal prosecution. 2023 Annual Report 27 Combination Products A combination product is a product composed of a combination of two or more FDA-regulated product components or products, e.g., drug-device or device-biologic.
Failure to comply with the applicable federal or state requirements could result in, among other things: (1) fines, injunctions, and civil penalties; (2) recall or seizure of products; (3) operating restrictions, partial suspension, or total shutdown of manufacturing; (4) refusing requests for approval of new products; (5) withdrawing approvals already granted; and (6) criminal prosecution. 26 United Therapeutics, a public benefit corporation Combination Products A combination product is a product composed of a combination of two or more FDA-regulated product components or products, e.g., drug-device or device-biologic.
Our drone delivery research efforts are focused on the development of piloted and autonomous electric vertical take-off and landing ( eVTOL ) aircraft systems to quickly, reliably, and sustainably deliver organs for transplant from manufacturing facilities to transplant centers.
Our organ delivery research efforts are focused on the development of piloted and autonomous electric vertical take-off and landing aircraft systems to quickly, reliably, and sustainably deliver organs and organ alternatives from manufacturing facilities to transplant centers.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIf these plans are not successfully and timely implemented, we could be unable to meet the growing demand for Tyvaso DPI, which would negatively impact our Tyvaso DPI revenues. 2023 Annual Report 37 • We may experience difficulty designing and implementing processes and procedures to ensure compliance with applicable regulations as we develop manufacturing operations for new products. • Natural and man-made disasters (such as fires, contamination, power loss, hurricanes, earthquakes, flooding, terrorist attacks, and acts of war), disease outbreaks, and pandemics such as COVID-19 impacting our internal and third-party manufacturing sites could cause a supply disruption. • The sterility and quality of our products could be substandard and such products could not be sold or used or could be subject to recalls. • The FDA and its international counterparts would require new testing and compliance inspections of new manufacturers of our products, or new manufacturing facilities we operate. • If we produce products that do not meet FDA-approved specifications and we fail to detect these issues prior to distribution of these products, our products may be the subject of safety alerts, product recalls, or other corrective actions, and we may be charged in product liability claims and lawsuits which, regardless of their ultimate outcome, could have a material adverse effect on our business and reputation and on our ability to attract and retain customers. • Regulatory agencies may not be able to timely inspect our facilities, or those of our third-party manufacturers, which could result in delays in obtaining necessary regulatory approvals for our products. • We may be unable to contract with needed manufacturers on satisfactory terms or at all. • The supply of materials and components necessary to manufacture and package our products may become scarce or unavailable, which could delay the manufacturing and subsequent sale of such products.
Biggest changeFurthermore, Unituxin has a limited shelf life, which impacts our ability to stockpile inventory at comparable levels to our other commercial products. • Natural and man-made disasters (such as fires, contamination, power loss, hurricanes, earthquakes, flooding, terrorist attacks, and acts of war), disease outbreaks, and pandemics such as COVID-19 impacting our internal and third-party manufacturing sites could cause a supply disruption. • The sterility and quality of our products could be substandard and such products could not be sold or used or could be subject to recalls. • The FDA and its international counterparts would require new testing and compliance inspections of new manufacturers of our products, or new manufacturing facilities we operate. • If we produce products that do not meet FDA-approved specifications and we fail to detect these issues prior to distribution of these products, our products may be the subject of safety alerts, product recalls, or other corrective actions, and we may be charged in product liability claims and lawsuits which, regardless of their ultimate outcome, could have a material adverse effect on our business and reputation and on our ability to attract and retain customers. • Regulatory agencies may not be able to timely inspect our facilities, or those of our third-party manufacturers, which could result in delays in obtaining necessary regulatory approvals for our products. • We may be unable to contract with needed manufacturers on satisfactory terms or at all. • The supply of materials and components necessary to manufacture and package our products may become scarce or unavailable, which in the past has delayed, and in the future could delay, the manufacturing and subsequent sale of such products.
Actions taken by the OIG, the DOJ or other agencies as a result of this industry-wide inquiry could reduce demand for our products and/or coverage of our products by federal and state health care. If any or all of these events occur, our business, prospects, and stock price could be materially and adversely affected.
Actions taken by the OIG, the DOJ, or other agencies as a result of this industry-wide inquiry could reduce demand for our products and/or coverage of our products by federal and state health care. If any or all these events occur, our business, prospects, and stock price could be materially and adversely affected.
If any of these systems require long-term repair or replacement, the impacted facility may not be able to manufacture product for a substantial period of time. • We and our third-party manufacturers rely upon local municipalities to supply our facilities with clean water, which is processed into high purity water and used as a key ingredient for several of our commercial drug products.
If any of these systems or equipment require long-term repair or replacement, the impacted facility may not be able to manufacture product for a substantial period of time. • We and our third-party manufacturers rely upon local municipalities to supply our facilities with clean water, which is processed into high purity water and used as a key ingredient for several of our commercial drug products.
Some of these competitors have substantially greater financial, marketing, manufacturing, sales, distribution, and technical resources, and a larger number of approved products, than we do. Some of these competitors also possess greater experience in areas critical to success such as research and development, clinical trials, sales and marketing, and regulatory matters. Numerous treatments currently compete with our commercial therapies.
Some of these competitors have substantially greater financial, marketing, manufacturing, sales, distribution, and technical resources, and a larger number of approved products, than we do. Some of these competitors also possess greater experience in areas critical to our success, such as research and development, clinical trials, sales and marketing, and regulatory matters. Numerous treatments compete with our commercial therapies.
If either of these two distributors places significantly larger or smaller orders in a given time period, our revenues can be materially impacted in a way that does not reflect patient demand. We rely entirely on third parties to supply pumps and other supplies necessary to administer Remodulin.
If either of these two distributors places significantly larger or smaller orders in a given time period, our revenues can be impacted in a way that does not reflect patient demand. We rely entirely on third parties to supply pumps and other supplies necessary to administer Remodulin.
As nebulized Tyvaso is a drug-device combination, we cannot sell nebulized Tyvaso without the Tyvaso Inhalation System. We also rely on various third parties to supply the monthly disposable device accessories that are used with the Tyvaso Inhalation System to administer nebulized Tyvaso. We currently rely entirely on MannKind to manufacture Tyvaso DPI finished drug product and inhalers for us.
As nebulized Tyvaso is a drug-device combination product, we cannot sell nebulized Tyvaso without the Tyvaso Inhalation System. We also rely on various third parties to supply the monthly disposable device accessories that are used with the Tyvaso Inhalation System. We currently rely entirely on MannKind to manufacture Tyvaso DPI finished drug product and inhalers for us.
Our xenotransplantation and regenerative medicine programs rely heavily on the use of animals to manufacture and test our products. Certain special interest groups categorically object to the use of animals for research purposes. Any negative attention, threats or acts of vandalism directed against our animal research activities could impede the operation of our business.
Our xenotransplantation and regenerative medicine programs rely heavily on the use of animals to manufacture and test our products. Certain special interest groups categorically object to the use of animals for research purposes. Any negative attention, threats, or acts of vandalism directed against our animal research or manufacturing activities could impede the operation of our business.
Such activities subject us to numerous federal, state, and local environmental and safety laws and regulations that govern the management, storage, and disposal of hazardous materials. Compliance with current and future environmental laws and regulations can require significant costs. The risk of accidental contamination or injury from these materials cannot be completely eliminated.
Such activities subject us to numerous federal, state, and local environmental and safety laws and regulations that govern the management, storage, and disposal of hazardous materials. Compliance with current and future environmental laws and regulations can require significant costs. The risk of accidental contamination or injury from these materials cannot be eliminated.
Historically, these were the pumps primarily used to administer Remodulin to patients in the United States. In 2021, we launched the Remunity Pump to administer subcutaneous Remodulin, and in 2022 ICU Medical made an alternative pump, the CADD-Solis, available for intravenous Remodulin. We rely entirely on DEKA and its affiliates to manufacture the Remunity Pump for Remodulin.
Historically, these were the pumps primarily used to administer Remodulin to patients in the United States. In 2021, we launched the Remunity Pump to administer subcutaneous Remodulin, and in 2022 ICU Medical made an alternative pump, the CADD-Solis, available for intravenous Remodulin. We rely entirely on DEKA and its affiliates to manufacture the Remunity and RemunityPRO Pumps.
We anticipate that the IRA and other healthcare reform measures that may be adopted in the future may result in additional downward pressure on the payment that we receive for any approved product, and adversely impact our business. Any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payment from commercial payers.
The IRA and other healthcare reform measures that may be adopted in the future may result in additional downward pressure on the payment that we receive for any approved product, and may adversely impact our business. Any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payment from commercial payers.
Any non-compliance, recall, or enforcement action issued against them could adversely impact our sales and operations. • The infrastructure of our internal manufacturing facilities, along with certain facilities of our third-party manufacturers, is aging. These facilities have highly sophisticated and complex utility systems.
Any non-compliance, recall, or enforcement action issued against them could adversely impact our sales and operations. • The infrastructure of our internal manufacturing facilities, along with certain facilities of our third-party manufacturers, is aging. These facilities have highly sophisticated and complex utility systems and manufacturing equipment.
Outside the United States, we rely substantially on our international distributors to obtain and maintain regulatory approvals for our products and to market and sell our products in compliance with applicable laws and regulations. In the United States, we derive substantially all of our treprostinil-based revenues from sales to two distributors, Accredo and CVS Specialty.
Outside the United States, we rely substantially on our international distributors to obtain and maintain regulatory approvals for our products and to market and sell our products in compliance with applicable laws and regulations. In the United States, we derive substantially all our treprostinil-based revenues from sales to two distributors, Accredo and CVS Specialty.
Actual or alleged cybersecurity incidents, including those caused by employee error, malfeasance, system failures, malware, ransomware, viruses, distributed denial of services attacks, credential harvesting, social engineering, and other forms of unauthorized access or disclosure to, or disrupting the operation of, our networks and systems or those of our customers, suppliers, vendors, and other service providers, can cause the loss, destruction, or unauthorized access or disclosure of data, including personal information of employees or confidential or proprietary information, disruption of our operations, and damage to our reputation, any of which could be costly to address and remediate and adversely affect our business, financial condition, or results of operations.
Actual or alleged cybersecurity incidents, including those caused by employee error, malfeasance, system failures, malware, ransomware, viruses, distributed denial of services attacks, credential harvesting, social engineering, and other forms of unauthorized access or disclosure to, or disrupting the operation of, our networks and systems or those of our customers, suppliers, vendors, and other service providers, can cause the loss, destruction, or unauthorized access or disclosure of data, including personal information of employees or confidential or proprietary information, disruption of our operations, and damage to our reputation and competitive position, any of which could be costly to address and remediate and adversely affect our business, financial condition, or results of operations.
The approval of new therapies may negatively impact sales of our current and potential new products. Sales may decrease if any third party that manufactures, markets, distributes, or sells our commercial products cannot do so satisfactorily, or we cannot manage our internal manufacturing processes.
The approval and launch of new therapies may negatively impact sales of our current and potential new products. Sales may decrease if any third party that manufactures, markets, distributes, or sells our commercial products cannot do so satisfactorily, or we cannot manage our internal manufacturing processes.
Finally, if demand for Tyvaso DPI does not meet our expectations, the revenue opportunity for our treprostinil products could be significantly lower than we expect. If our products fail in clinical trials, we will be unable to sell those products.
Finally, if demand for our Tyvaso products does not meet our expectations, the revenue opportunity for our treprostinil products could be significantly lower than we expect. If our products fail in clinical trials, we will be unable to sell those products.
The price of our common stock could decline sharply due to general market conditions as well as the following factors, among others: • quarterly and annual financial results and any failure to meet our expectations or those of securities analysts; • timing of enrollment and results of our clinical trials; • announcements regarding generic or other challenges to the intellectual property related to our products, the launch of generic versions of our products or other competitive products, such as sotatercept or Yutrepia, and the impact of competition from generic and other products on our revenues; • announcements regarding litigation matters, including our ongoing litigation with Liquidia, among others; • announcements regarding our efforts to obtain regulatory approval of, and to launch commercial sales of, new products; • physician, patient, investor, or public concerns regarding the efficacy and/or safety of products marketed or being developed by us or by others; • changes in, or new laws and regulations affecting reimbursement of, our therapeutic products by government payers, changes in reimbursement policies of private insurance companies, including the implementation and impacts of the IRA, and negative publicity surrounding the cost of high-priced therapies; • announcements of technological innovations or new products or announcements regarding our existing products, including in particular the development of new, competing therapies; • substantial sales of our common stock by us or our existing shareholders, or concerns that such sales may occur; • future issuances of common stock by us or other activity which could be viewed as being dilutive to our shareholders; • rumors or incorrect statements by investors and/or analysts concerning our company, our products, or our operations; • failures or delays in our efforts to obtain or maintain domestic or international regulatory approvals; • discovery of previously unknown problems with our marketed products, or problems with our manufacturing, regulatory, compliance, promotional, marketing, or sales activities that result in regulatory penalties or restrictions on our products, up to the withdrawal of our products from the market; and • accumulation of significant short positions in our common stock by hedge funds or other investors or the significant accumulation of our common stock by hedge funds or other institutional investors with investment strategies that may lead to short-term holdings.
The price of our common stock could decline sharply due to general market conditions as well as the following factors, among others: • quarterly and annual financial results and any failure to meet our expectations or those of securities analysts; • timing of enrollment and results of our clinical trials; 46 United Therapeutics, a public benefit corporation • announcements regarding generic or other challenges to the intellectual property related to our products, the launch of generic versions of our products or other competitive products, such as Yutrepia, and the impact of competition from generic and other products on our revenues; • announcements regarding litigation matters, including our ongoing litigation with Liquidia, among others; • announcements regarding our efforts to obtain regulatory approval of, and to launch commercial sales of, new products; • physician, patient, investor, or public concerns regarding the efficacy and/or safety of products marketed or being developed by us or by others; • changes in, or new laws and regulations affecting reimbursement of, our therapeutic products by government payers, changes in reimbursement policies of private insurance companies, including the implementation and impacts of the IRA, and negative publicity surrounding the cost of high-priced therapies; • announcements of technological innovations or new products or announcements regarding our existing products, including in particular the development of new, competing therapies; • substantial sales of our common stock by us or our existing shareholders, or concerns that such sales may occur; • future issuances of common stock by us or other activity which could be viewed as being dilutive to our shareholders; • rumors or incorrect statements by investors and/or analysts concerning our company, our products, or our operations; • failures or delays in our efforts to obtain or maintain domestic or international regulatory approvals; • discovery of previously unknown problems with our marketed products, or problems with our manufacturing, regulatory, compliance, promotional, marketing, or sales activities that result in regulatory penalties or restrictions on our products, up to the withdrawal of our products from the market; and • accumulation of significant short positions in our common stock by hedge funds or other investors or the significant accumulation of our common stock by hedge funds or other institutional investors with investment strategies that may lead to short-term holdings.
Our clinical trials have been and in the future may be discontinued, delayed, canceled, or disqualified for various reasons, including: (1) pandemics such as the COVID-19 pandemic, which initially caused us to suspend enrollment of most of our clinical studies; (2) the drug is unsafe or ineffective, or physicians and/or patients believe that the drug is unsafe or ineffective, or that other therapies are safer, more effective, better tolerated, or more convenient; (3) patients do not enroll in or complete clinical trials at the rate we expect, due to the availability of alternative therapies, the enrollment of competing clinical trials, or other reasons; (4) we, or clinical trial sites or other third parties do not adhere to trial protocols and required quality controls under good clinical practices ( GCP ) regulations and similar regulations outside the United States; (5) patients experience severe side effects during treatment or die during our trials because of adverse events; and (6) the results of clinical trials conducted in a particular country are not acceptable to regulators in other countries.
Our clinical trials have been and in the future may be discontinued, delayed, canceled, or disqualified for various reasons, including: (1) pandemics such as the COVID-19 pandemic, which initially caused us to suspend enrollment of most of our clinical studies; (2) manufacturing and supply chain disruptions; (3) the drug is unsafe or ineffective, or physicians and/or patients believe that the drug is unsafe or ineffective, or that other therapies are safer, more effective, better tolerated, or more convenient; (4) patients do not enroll in or complete clinical trials at the rate we expect, due to the availability of alternative therapies, the enrollment of competing clinical trials, or other reasons; (5) we, or clinical trial sites or other third parties, do not adhere to trial protocols and required quality controls under good clinical practices ( GCP ) regulations and similar regulations outside the United States; (6) patients experience severe side effects during treatment or die during our trials because of adverse events; and (7) the results of clinical trials conducted in a particular country are not acceptable to regulators in other countries.
If granted, product approvals can be conditioned on the completion of post-marketing clinical studies, accompanied by significant restrictions on the use or marketing of a given product and withdrawn for failure to comply with regulatory requirements, such as post-marketing requirements and post-marketing commitments, or upon the occurrence of adverse events subsequent to commercial introduction.
If granted, product approvals can be conditioned on the completion of post-marketing clinical studies, accompanied by significant restrictions on the use or marketing of a given product and withdrawn for failure to comply with regulatory requirements, such as post-marketing requirements and post-marketing commitments, or upon the occurrence of adverse effects subsequent to commercial introduction.
We may not be able to effect any such alternative measures on commercially reasonable terms or at all and, even if successful, such actions may not enable us to meet any such debt service obligations. In addition, our ability to withstand competitive pressures and to react to changes in our industry could be impaired.
We may not be able to implement any such alternative measures on commercially reasonable terms or at all and, even if successful, such actions may not enable us to meet any such debt service obligations. In addition, our ability to withstand competitive pressures and to react to changes in our industry could be impaired.
Cybersecurity incidents and other disruptions impacting our networks, systems, or data may have a material adverse effect on our business. We are increasingly dependent on information technology systems and infrastructure, much of which is outsourced to third parties including in “cloud”-based platforms.
Cybersecurity incidents and other disruptions impacting our networks, systems, or data may have a material adverse effect on our business. We are increasingly dependent on information technology systems and infrastructure, much of which is outsourced to third parties including in cloud-based platforms.
When such disclosures occur, we may fail to monitor and comply with applicable adverse event reporting obligations or we may not be able to defend against political and market pressures generated by social media due to restrictions on what we may say about our products.
When such disclosures occur, we may fail to monitor and comply with applicable adverse effect reporting obligations or we may not be able to defend against political and market pressures generated by social media due to restrictions on what we may say about our products.
There are a limited number of pumps available in the market, and the discontinuation of any particular pump could have a material, adverse impact on our Remodulin revenues if a viable supply of an alternate pump is not available.
There are a limited number of pumps and other supplies available in the market, and the discontinuation of any particular pump could have a material, adverse impact on our Remodulin revenues if a viable supply of an alternate pump is not available.
These lawsuits, or other lawsuits in the future, could result in significant monetary judgements and the imposition of other penalties against us. Members of Congress have called upon the OIG to issue revised guidance about patient assistance programs.
These lawsuits, or other lawsuits in the future, could result in significant monetary judgments and the imposition of other penalties against us. Members of Congress have called upon the OIG to issue revised guidance about patient assistance programs.
Third parties assist us in activities critical to our operations, such as: (1) manufacturing our clinical and commercial products; (2) conducting clinical trials, preclinical studies, and other research and development activities; (3) obtaining regulatory approvals; (4) conducting pharmacovigilance and product complaint activities, including adverse event reporting, and handling product complaints; (5) obtaining medical device clearances and approvals for the devices used to administer our drugs; and (6) marketing and distributing our products.
Third parties assist us in activities critical to our operations, such as: (1) manufacturing our clinical and commercial products; (2) conducting clinical trials, preclinical studies, and other research and development activities; (3) obtaining regulatory approvals; (4) conducting pharmacovigilance and product complaint activities, including handling and reporting of adverse effects (including adverse events and product complaints); (5) obtaining medical device clearances and approvals for the devices used to administer our drugs; and (6) marketing and distributing our products.
Our bylaws provide that, to the fullest extent permitted by law, unless we agree in writing to an alternative forum, (1) the Delaware Court of Chancery (or, if such court does not have, or declines to accept, jurisdiction, another state court or a federal court located in Delaware) will be the exclusive forum for any complaint asserting any internal corporate claims, including claims in the right of the corporation based upon a violation of a duty by a current or former director, officer, employee, or stockholder in such capacity, or as to which the Delaware General Corporation Law confers jurisdiction upon the Court of Chancery, and (2) the federal district courts will be the exclusive forum for any complaint asserting a cause of action arising under the Securities Act of 1933, as amended.
Our bylaws provide that, to the fullest extent permitted by law, unless we agree in writing to an alternative forum, (1) the Delaware Court of Chancery (or, if such court does not have, or declines to accept, jurisdiction, another state court or a 2024 Annual Report 47 federal court located in Delaware) will be the exclusive forum for any complaint asserting any internal corporate claims, including claims in the right of the corporation based upon a violation of a duty by a current or former director, officer, employee, or shareholder in such capacity, or as to which the Delaware General Corporation Law confers jurisdiction upon the Court of Chancery, and (2) the federal district courts will be the exclusive forum for any complaint asserting a cause of action arising under the Securities Act of 1933, as amended.
External factors, such as compliance with law, may also impact the successful integration of an acquired business. Acquisitions could involve dilutive issuances of equity securities, the incurrence of debt, one-time write-offs of goodwill, and substantial amortization expenses of other intangible assets.
External factors, such as compliance with law, may also impact the successful integration of an acquired business. Acquisitions could involve dilutive issuances of equity securities, the incurrence of debt, one-time write-offs of goodwill (or IPR&D assets), and substantial amortization expenses of other intangible assets.
Our industry is highly regulated and changes in law or government health care programs may adversely impact our business, operations, or financial results. We cannot predict how future federal or state legislative or administrative changes related to healthcare reform will affect our business.
Our industry is highly regulated and changes in law or government health care programs, like Medicaid or Medicare, may adversely impact our business, operations, or financial results. We cannot predict how future federal or state legislative or administrative changes related to healthcare reform will affect our business.
The IRA permits the Secretary of the Department of Health and Human Services ( HHS ) to implement many of these provisions through guidance, as opposed to regulation, for the initial years. HHS has issued guidance, and is expected to continue to issue guidance, even while lawsuits challenging the IRA remain pending.
The IRA permits the Secretary of the Department of Health and Human Services ( HHS ) to implement many of these provisions through guidance, as opposed to regulation, for the initial years. HHS has issued guidance, and is expected to continue to issue guidance, even while multiple lawsuits challenging the IRA negotiation requirement remain pending.
In addition, some states have imposed restrictions on manufacturer co-pay programs when therapeutic 2023 Annual Report 43 equivalents are available. Growing use of such programs, or new laws limiting manufacturer ability to provide co-pay assistance, could affect patient access to our products and limit product utilization, which may, in turn, adversely affect our business, prospects, and stock price.
In addition, some states have imposed restrictions on manufacturer co-pay programs when therapeutic equivalents are available. Growing use of such programs, or new laws limiting manufacturer ability to provide co-pay assistance, could affect patient access to our products and limit product utilization, which may, in turn, adversely affect our business, prospects, and stock price.
There is also a risk of inappropriate disclosure of sensitive information or negative or inaccurate comments about us on any social networking website. If any of these events occur or we otherwise fail to comply with applicable regulations, we could incur liability, face overly restrictive regulatory actions, or incur other harm to our business.
There is also a risk of inappropriate disclosure of sensitive information or negative or inaccurate comments about us on any social networking website. If any of these events occur or we otherwise 2024 Annual Report 43 fail to comply with applicable regulations, we could incur liability, face overly restrictive regulatory actions, or incur other harm to our business.
We may not be able to generate sufficient cash to service or repay our indebtedness, which may have a material adverse effect on our financial position, results of operations, and cash flows. We may borrow up to $2.0 billion under our Credit Agreement, which matures in March 2028. Currently, our outstanding principal balance is $700.0 million.
We may not be able to generate sufficient cash to service or repay our indebtedness, which may have a material adverse effect on our financial position, results of operations, and cash flows. We may borrow up to $2.0 billion under our Credit Agreement, which matures in March 2029. Currently, our outstanding principal balance is $300.0 million.
Reports of actual or perceived side effects and adverse events associated with our products could cause our sales to decrease or regulatory approvals to be revoked.
Reports of actual or perceived side effects and other adverse effects associated with our products could cause our sales to decrease or regulatory approvals to be revoked.
Our ability to repay or refinance our debt obligations under our Credit Agreement and any future debt that we may incur will depend on our financial condition and operating performance, which are subject to a number of factors beyond our control.
Our ability to repay or refinance our debt obligations under our Credit Agreement and any future debt that we may incur will depend on our financial condition and operating performance, which are subject to factors beyond our control.
Department of Agriculture, and their international counterparts, as applicable. The process of obtaining and maintaining regulatory approvals for new drugs, biologics, and medical devices is lengthy, expensive, and uncertain. The regulatory approval process is particularly uncertain for our transplantation programs, which include the development of xenotransplantation, regenerative medicine, 3-D organ bioprinting, and cell-based products.
Department of Agriculture, and their international counterparts, as applicable. The process of obtaining and maintaining regulatory approvals for new drugs, biologics, and medical devices is lengthy, expensive, and uncertain. The regulatory approval process is particularly uncertain for our transplantation programs, which include the development of xenotransplantation, regenerative medicine, 3D bioprinting of organ alternatives, and cell-based products.
These restrictive change of control provisions could impede or prevent mergers or other transactions that could benefit our shareholders. 2023 Annual Report 47 Our shareholders must rely on stock appreciation for any return on their investment in us. We have never paid, and do not intend to pay, cash dividends.
These restrictive change of control provisions could impede or prevent mergers or other transactions that could benefit our shareholders. Our shareholders must rely on stock appreciation for any return on their investment in us. We have never paid, and do not intend to pay, cash dividends.
The increasing use of social media platforms presents new risks and challenges. Social media is increasingly being used to communicate information about our products and the diseases that our therapies are designed to treat. Social media practices in our industry continue to evolve and regulations related to such use are not always clear.
The increasing use of social media platforms and artificial intelligence-based software presents new risks and challenges. Social media is increasingly being used to communicate information about our products and the diseases that our therapies are designed to treat. Social media practices in our industry continue to evolve and regulations related to such use are not always clear.
If we fail to attract and retain such employees, we may not be successful in developing and commercializing new therapies. Risks Related to Legal Compliance We must comply with extensive laws and regulations in the United States and other countries.
If we fail to attract and retain such employees, we may not be successful in developing and commercializing new therapies. 2024 Annual Report 39 Risks Related to Legal Compliance We must comply with extensive laws and regulations in the United States and other countries.
The final rule allows certain prescription drugs to be imported from Canada, and the guidance describes procedures for drug manufacturers to facilitate the importation of FDA-approved drugs and biologics manufactured abroad and originally intended for sale in a foreign country into the United States. The FDA recently approved Florida’s drug importation plan.
The final rule allows certain prescription drugs to be imported from Canada, and the guidance 2024 Annual Report 41 describes procedures for drug manufacturers to facilitate the importation of FDA-approved drugs and biologics manufactured abroad and originally intended for sale in a foreign country into the United States. In January 2024, the FDA approved Florida’s drug importation plan.
The price of common stock can be highly volatile within the pharmaceutical and biotechnology sector. Consequently, significant price and volume fluctuations in the market may not relate to operating performance.
Risks Related to Our Common Stock The price of our common stock can be highly volatile and may decline. The price of common stock can be highly volatile within the pharmaceutical and biotechnology sector. Consequently, significant price and volume fluctuations in the market may not relate to operating performance.
Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things: bring more transparency to drug pricing; reduce the cost of prescription drugs under government payer programs; review the relationship between pricing and manufacturer patient programs; and reform government program reimbursement methodologies for drugs.
Among other things, there have been several U.S. Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things: bring more transparency to drug pricing; reduce the cost of prescription drugs under government payer programs; review the relationship between pricing and manufacturer patient programs; and reform government program reimbursement methodologies for drugs.
Because the tools and methods used by threat actors to damage or obtain unauthorized access to networks, systems, and data change frequently, and are often not known until used against a target, we may be unable to anticipate these tools or methods or implement adequate preventative measures.
Because the tools and methods — including those deploying artificial intelligence technology — used by threat actors to damage or obtain unauthorized access to networks, systems, and data change frequently, and are often not known until used against a target, we may be unable to anticipate these tools or methods or implement adequate preventative measures.
We also rely entirely on Gilero to manufacture cartridges that were recently cleared by the FDA for use with the MS-3 pump to administer Remodulin. For a further discussion of risks created by the use of third-party contract manufacturers, see the risk factor above entitled, Our manufacturing strategy exposes us to significant risks .
Finally, we rely entirely on Sanner GmbH (which recently acquired Gilero LLC) to manufacture cartridges that were cleared by the FDA for use with the MS-3 pump to administer Remodulin. For a further discussion of risks created by the use of third-party contract manufacturers, see the risk factor above entitled, Our manufacturing strategy exposes us to significant risks .
If MannKind is unable to manufacture Tyvaso DPI in sufficient quantities for us for any reason, our commercial sales of Tyvaso DPI could be materially and adversely impacted. Finally, we also rely on various sole-source suppliers for manufacturing activities related to ralinepag and other pumps we are developing for Remodulin.
If MannKind is unable to manufacture Tyvaso DPI in sufficient quantities for us for any reason, our commercial sales of Tyvaso DPI could be materially and adversely impacted. We also rely on various sole-source suppliers for manufacturing activities related to ralinepag.
Sanctions under these federal and state laws may include treble civil monetary penalties, payment of damages, fines, exclusion of our products from reimbursement under federal health care programs, imprisonment, and the curtailment or restructuring of our operations. Government healthcare reform and other reforms could adversely affect our revenue, costs, and results of operations.
Sanctions under these federal and state laws may include treble civil monetary penalties, payment of damages, fines, exclusion of our products from reimbursement under federal health care programs, imprisonment, and the curtailment or restructuring of our operations. 40 United Therapeutics, a public benefit corporation Government healthcare reform and other reforms could adversely affect our revenue, costs, and results of operations.
In November 2021, the court granted our motion for summary judgment, ruling that the letters threatening enforcement action “contain legal reasoning that rests upon an erroneous reading of Section 340B.” HRSA has appealed, and the appellate court’s decision is pending.
In November 2021, the court granted our motion for summary judgment, ruling that the letters threatening enforcement action “contain legal reasoning that rests upon an erroneous reading of Section 340B.” HRSA appealed, and the appellate court affirmed the lower court’s decision in our favor.
In addition, there is currently limited case law involving PBCs (including case law interpreting and applying the balancing obligation of PBC directors), which may expose us to additional litigation risk generally until additional case law develops or additional legislative action is taken.
In addition, there is currently limited case law involving PBCs (including case law interpreting and applying the balancing obligation of PBC directors), which may expose us to additional litigation risk generally until additional case law develops or additional legislative action is taken. Item 1B. Unresolved Staff Comments None.
It is difficult to predict the impact, if any, of any such legislation or executive actions on the use of and reimbursement for our products in the United States, including the potential for the importation of generic versions of our products.
It is difficult to predict the impact, if any, that future legislation or executive actions might have on the use of and reimbursement for our products in the United States, including the potential for the importation of generic versions of our products.
Nonetheless, certain 340B covered entities and HHS, in a non-binding (and now-retracted) Advisory Opinion, stated that, in their view, manufacturers in the 340B program are obligated to sell 340B drugs at the 340B ceiling prices to all contract pharmacies acting as agents of a covered entity.
Nonetheless, the HHS, in a non-binding (and now-retracted) Advisory Opinion, stated that manufacturers in the 340B program are obligated to sell their covered outpatient drugs at the 340B ceiling price to all contract pharmacies acting as agents of a covered entity.
If Lilly is unable to manufacture or supply Adcirca or its distribution network is disrupted, it could delay, disrupt, or prevent us from selling Adcirca. We rely on two contract manufacturers — Minnetronix Inc. and Phillips-Medisize Corp. — to manufacture the Tyvaso Inhalation System for nebulized Tyvaso.
If Lilly is unable to manufacture or supply Adcirca or its distribution network is disrupted, it could delay, disrupt, or prevent us from selling Adcirca. 38 United Therapeutics, a public benefit corporation We rely on two contract manufacturers — Minnetronix Inc. and Phillips-Medisize Corp. — to manufacture the Tyvaso Inhalation System for nebulized Tyvaso.
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap; imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023); and replaces the Medicare Part D coverage gap discount program with a new discounting program (beginning in 2025).
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare, with prices that can be negotiated subject to a cap (with resulting prices for the initial ten drugs first effective in 2026); imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023); redesigns the Medicare Part D benefit (beginning in 2024); and replaces the Medicare Part D coverage gap discount program with a new manufacturer discounting program (beginning in 2025).
Although we do not directly source any raw materials or consumables from Ukraine, Russia, Belarus, Gaza, or Israel, our European- and Middle East-based suppliers and service providers could be impacted by extended conflicts or an escalation of these conflicts into neighboring countries. • The cost of many key raw materials and consumables used in the manufacture of our products has increased due to significant inflationary pressure.
Although we do not directly source any raw materials or consumables from Ukraine, Russia, Belarus, Gaza, Lebanon, or Israel, our European- and Middle East-based suppliers and service providers could be impacted by extended conflicts or an escalation of these conflicts into neighboring countries. • The cost of many key raw materials and consumables used in the manufacture of our products has increased due to significant inflationary pressure, and could increase further as a result of tariffs enacted by the Trump administration.
Reports of side effects and adverse events associated with our products could affect a physician’s decision to prescribe or a patient’s willingness to use our products, which may have a significant adverse impact on sales of our products.
Reports of adverse effects (including side effects and other adverse events, as well as product complaints) associated with our products could affect a physician’s decision to prescribe or a patient’s willingness to use our products, which may have a significant adverse impact on sales of our products.
Once approved, the manufacture, distribution, advertising, and marketing of our products are subject to extensive regulation, including requirements related to product labeling, pharmacovigilance and adverse event and medical device reporting, complaint processing, storage, distribution, and record-keeping. Our product candidates have in the past and may in the future fail to receive regulatory approval.
Once approved, the manufacture, distribution, advertising, and marketing of our products are subject to extensive regulation, including requirements related to product labeling, pharmacovigilance and adverse effect reporting and processing (including both adverse events and product complaints), storage, distribution, and record-keeping. Our product candidates have in the past and may in the future fail to receive regulatory approval.
Patients and doctors may discontinue use of our products if they perceive competing products as safer, more effective, less invasive, more convenient, and/or less expensive than ours. Doctors may reduce the prescribed doses of our products if they 36 United Therapeutics, a public benefit corporation prescribe them in combination with competing products.
Patients and doctors may discontinue use of our products if they perceive competing products as safer, more effective, less invasive, more convenient, and/or less expensive than ours. Doctors may reduce the prescribed doses of our products if they prescribe them in combination with competing products.
We are required to report certain adverse events to the FDA and its international counterparts. Development of new products, and 2023 Annual Report 39 new formulations and indications for existing products, could result in new side effects and adverse events which may be serious in nature.
We are required to report certain adverse effects to the FDA and its international counterparts. Development of new products, and new formulations, indications, and delivery devices for existing products, could result in new side effects and other adverse effects which may be serious in nature.
This evolution creates uncertainty and risk of noncompliance. For example, patients and others may use social media channels to comment on the effectiveness of a product or to report an alleged adverse event.
This evolution creates uncertainty and risk of noncompliance. For example, patients and others may use social media channels to comment on the effectiveness of a product or to report alleged adverse effects, such as adverse events and product complaints.
When our patents expire, competitors may develop generic versions of our products and market them at a lower price. Competitors may also seek to design around our patents or exclude patented methods of treatment, such as patent-protected indications, from the label for generic versions of our products in an effort to develop competing products that do not infringe our patents.
Competitors may also seek to design around our patents or exclude patented methods of treatment, such as patent-protected indications, from the label for generic versions of our products in an effort to develop competing products that do not infringe our patents.
District Court for the District of Columbia. In September 2021, HRSA sent to us, along with the other manufacturers challenging HRSA’s 340B interpretation, letters stating that HRSA was referring this issue to the OIG for potential enforcement action. We have not had any communication from the OIG regarding our 340B contract pharmacy policy.
In September 2021, HRSA sent to us, along with the other manufacturers challenging HRSA’s 340B interpretation, letters stating that HRSA was referring this issue to the OIG for potential enforcement action. We have not had any communication from the OIG regarding our 340B 42 United Therapeutics, a public benefit corporation contract pharmacy policy.
For example, we are engaged in significant efforts to expand MannKind’s capacity to manufacture Tyvaso DPI in the near term, at our expense. Longer-term, we are constructing our own facility to manufacture Tyvaso DPI.
For 36 United Therapeutics, a public benefit corporation example, we are engaged in significant efforts to expand MannKind’s capacity to manufacture Tyvaso DPI in the near term, at our expense. Longer-term, we are constructing our own facility to manufacture Tyvaso DPI.
We must comply with various laws in jurisdictions around the world that restrict certain marketing practices. Our business activities may be subject to challenge under laws in jurisdictions around the world restricting particular marketing practices, such as: • Anti-kickback and false claim statutes, the Foreign Corrupt Practices Act, and the United Kingdom Bribery Act.
Our business activities may be subject to challenge under laws in jurisdictions around the world restricting marketing practices, such as: • Anti-kickback and false claim statutes, the Foreign Corrupt Practices Act, and the United Kingdom Bribery Act.
The IRA discounting program that will replace the coverage gap discount program will also increase financial obligations of Part D prescription drug plans with respect to beneficiaries in the catastrophic coverage phase. This may incentivize Part D prescription drug plans to seek greater price concessions from us in order to include our products on their formularies.
The manner in which CMS has implemented the manufacturer discounting program will also increase financial obligations of Part D prescription drug plans with respect to beneficiaries in the catastrophic coverage phase. This may incentivize Part D prescription drug plans to seek greater price concessions from us in order to include our products on their formularies.
Due to the nature of our products, alternative suppliers may not be readily available, causing us to rely solely on internal capabilities to meet future demand. • In 2024, we plan to begin operating a clinical scale, designated pathogen-free facility ( DPF ) to produce our xenotransplantation products for human clinical studies.
Due to the nature of our products, alternative suppliers may not be readily available, causing us to rely solely on internal capabilities to meet future demand. • In 2024, we began operating a clinical-scale, designated pathogen-free facility ( DPF ) to produce our xenotransplantation products for human clinical studies. This facility houses gene-edited pigs in a highly controlled containment environment.
Third parties have challenged, and may in the future challenge, the validity of our patents, through patent litigation and/or initiating proceedings, including re-examinations, IPRs, post-grant reviews, and interference proceedings, before the USPTO or other applicable patent filing offices, or other means. For example, Liquidia is challenging various patents related to nebulized Tyvaso and our other treprostinil-related patents.
Third parties have challenged, and may in the future challenge, the validity of our patents, through patent litigation and/or initiating proceedings, including re-examinations, IPRs, post-grant reviews, and interference proceedings, before the USPTO or other applicable patent filing offices, or other means.
Our net revenues could also be negatively impacted by pricing pressure as a result of competitive challenges, the IRA, and other drug price reduction initiatives. The current and expected availability of generic versions of our products has decreased, and may continue to decrease, our revenues.
Our net revenues could also be negatively impacted by pricing pressure as a result of competitive challenges, the IRA, and other drug price reduction initiatives. The availability of generic versions of our products has negatively impacted our revenues, and these and additional generic products launched in the future may continue to do so.
The availability of generic treprostinil injection in the United States could materially impact our revenues, and generic competition has materially impacted our Remodulin revenues outside the United States. Our competitors are also developing new products that may compete with ours.
The availability of generic treprostinil injection in the United States could materially impact our revenues, and generic competition materially impacted our Remodulin revenues outside the United States. Our competitors are also developing numerous new products that may compete with ours, including products intended to treat PAH and/or PH-ILD.
In addition to continuing pressure on prices and cost containment measures, legislative developments at the European Union ( EU ) or member state level may result in significant additional requirements or obstacles that may increase operating costs.
Similar political, economic, and regulatory developments are occurring in other countries and may affect our profitability. In addition to continuing pressure on prices and cost containment measures, legislative developments at the European Union ( EU ) or member state level may result in significant additional requirements or obstacles that may increase operating costs.
There are also two therapies approved for the treatment of IPF, and a significant number of additional therapies being developed for the treatment of IPF, which would compete with Tyvaso DPI and nebulized Tyvaso if they are ultimately approved for that indication.
There are also two therapies approved for the treatment of IPF, and we are aware of a 2024 Annual Report 35 significant number of additional therapies being developed for the treatment of IPF, which would compete with Tyvaso DPI and nebulized Tyvaso if either of them is ultimately approved for that indication.
In December 2017, we entered into a civil Settlement Agreement with the U.S. Government to resolve a DOJ investigation of our support of non-profit patient assistance programs and paid $210.0 million, plus interest, to the U.S. Government upon settlement.
Government to resolve a DOJ investigation of our support of non-profit patient assistance programs and paid $210.0 million, plus interest, to the U.S. Government upon settlement.
Changes in suppliers and/or service providers could interrupt the manufacturing of our commercial products and impede the progress of our commercial launch plans and clinical trials. Our internal manufacturing process subjects us to risks as we engage in increasingly complex manufacturing processes.
Changes in suppliers and/or service providers could interrupt the manufacturing of our commercial products and impede the progress of our commercial launch plans and clinical trials. Our internal manufacturing process subjects us to risks as we engage in increasingly complex manufacturing processes. We manufacture our entire supply of Orenitram and Unituxin without an FDA-approved back-up manufacturing site.
Under the new program, manufacturers must give a 10 percent discount on Part D drugs in the initial coverage phase, and a 20 percent discount on Part D drugs in the so-called “catastrophic phase” (the phase after the patient incurs costs above the initial phase out-of-pocket threshold, which will be $2,000 beginning in 2025).
Under the Medicare Part D manufacturer discounting program that became effective January 1, 2025 pursuant to the IRA, manufacturers must give a 10 percent discount on Part D drugs in the initial coverage phase, and a 20 percent discount on Part D drugs in the so-called “catastrophic phase” (the phase after the patient incurs costs above the initial phase out-of-pocket threshold, which is $2,000 beginning in 2025).
We and certain other manufacturers initiated litigation challenging the Advisory Opinion and HRSA’s position on contract pharmacies generally. HHS subsequently withdrew the Advisory Opinion, but HRSA issued letters to manufacturers, including us, threatening enforcement action if the manufacturers do not abandon their 340B contract pharmacy policies. We filed suit against HHS and HRSA in June 2021 in the U.S.
HHS subsequently withdrew the Advisory Opinion, but HRSA issued letters to manufacturers, including us, threatening enforcement action if the manufacturers do not abandon their 340B contract pharmacy policies. We filed suit against HHS and HRSA in June 2021 in the U.S. District Court for the District of Columbia.
Further, certain acquisitions may be subject to regulatory approval, which can be time consuming and costly to obtain or may be denied, and if obtained, the terms of such regulatory approvals may limit our ongoing operations or require us to divest assets. 46 United Therapeutics, a public benefit corporation Risks Related to Our Common Stock The price of our common stock can be highly volatile and may decline.
Further, certain acquisitions may be subject to regulatory approval, which can be time consuming and costly to obtain or may be denied, and if obtained, the terms of such regulatory approvals may limit our ongoing operations or require us to divest assets.
Our manufacturing strategy exposes us to significant risks. We must be able to manufacture sufficient quantities of our commercial products to satisfy demand. We manufacture nebulized Tyvaso drug product, Remodulin, Orenitram, and Unituxin, including the active ingredient in each of these products, at our own facilities and rely on third parties for additional manufacturing capacity for nebulized Tyvaso and Remodulin.
We manufacture nebulized Tyvaso drug product, Remodulin, Orenitram, and Unituxin, including the active ingredient in each of these products (and in Tyvaso DPI), at our own facilities and rely on third parties for additional manufacturing capacity for nebulized Tyvaso and Remodulin.
The impact on Tyvaso DPI and Orenitram revenues could be offset by an increase in the number of patients able to afford these therapies, but the amount of offset, if any, is inherently uncertain and difficult to predict.
The impact on Tyvaso DPI and Orenitram revenues could be offset because the IRA’s redesign of certain Part D components, some of which went into effect in 2024, resulted in an increase in the number of patients able to afford these therapies. The amount of the offset, if any, is inherently uncertain and difficult to predict.
Failure to follow applicable 40 United Therapeutics, a public benefit corporation rules and guidelines related to promotion and advertising can result in the adverse regulatory actions by the FDA and its international counterparts — such as warning letters, enforcement actions, civil lawsuits, or criminal prosecution.
Failure to follow applicable rules and guidelines related to promotion and advertising can result in the adverse regulatory actions by the FDA and its international counterparts — such as warning letters, enforcement actions, civil lawsuits, or criminal prosecution. We must comply with various laws in jurisdictions around the world that restrict certain marketing practices.
Patent litigation can be time consuming, distracting, and costly, and the outcome may be difficult to predict and unfavorable to us. If we are unsuccessful in the defense of our patents, our business could be negatively impacted. We also rely on trade secrets to protect our proprietary know-how and other confidential technological advances.
If we are unsuccessful in the defense of our patents, our business could be negatively impacted. 44 United Therapeutics, a public benefit corporation We also rely on trade secrets to protect our proprietary know-how and other confidential technological advances.
The period under which our commercial and developmental therapies are protected by our patent rights is limited. Three of our U.S. patents covering our current methods of synthesizing and producing treprostinil expired in October 2017, and three more will expire in 2028. Our patents related to our individual treprostinil-based products expire at various times between 2024 and 2042.
The period under which our commercial and developmental therapies are protected by our patent rights is limited. Our patents related to our individual treprostinil-based products expire at various times through 2042.
It is impossible to eliminate all cybersecurity threats and exposure to cybersecurity incidents, and thus our networks and systems, as well as those of our service providers, suppliers, customers and other third parties, remain potentially vulnerable to known or unknown threats. 2023 Annual Report 45 Risks Related to Our Financing Capacity, Indebtedness, and Investments If we need additional financing and cannot obtain it, our product development and sales efforts may be limited.
It is impossible to eliminate all cybersecurity threats and exposure to cybersecurity incidents, and thus our networks and systems, as well as those of our service providers, suppliers, customers and other third parties, remain potentially vulnerable to known or unknown threats.
A U.S. patent for Adcirca for the treatment of pulmonary hypertension expired in November 2017, and FDA-conferred regulatory exclusivity expired in May 2018, leading to the launch of a generic version of Adcirca in August 2018. We have no issued patents or pending patent applications covering Unituxin.
Other actions against us in the future could result in significant monetary judgments and the imposition of other penalties against us. A U.S. patent for Adcirca for the treatment of pulmonary hypertension expired in November 2017, and FDA-conferred regulatory exclusivity expired in May 2018, leading to the launch of a generic version of Adcirca in August 2018.
The IRA allows the 10 and 20 percent discounts to be 2023 Annual Report 41 phased in over time for certain drugs for “specified small manufacturers.” In January 2024, CMS provided a preliminary, non-binding notification that we were deemed a specified small manufacturer. We are still evaluating the potential impact of this status on our revenues.
The IRA allows the 10 and 20 percent discounts to be phased in over time for certain drugs for “specified small manufacturers.” In April 2024, CMS informed us that we are deemed to be a specified small manufacturer.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeItem 1C. Cybersecurity We have implemented a cybersecurity program consistent with industry practices to assess, identify, and manage risks from cybersecurity threats that may result in adverse effects on the confidentiality, integrity, and availability of our networks, systems, and data.
Biggest changeCybersecurity We have implemented a cybersecurity program consistent with industry practices to assess, identify, and manage risks from cybersecurity threats that may result in adverse effects on the confidentiality, integrity, and availability of our networks, systems, and data. 48 United Therapeutics, a public benefit corporation Governance Board of Directors Our board of directors exercises its oversight role through its Audit Committee, which has primary responsibility for overseeing risks related to cybersecurity matters.
These plans outline a coordinated approach for protecting information security, managing vulnerabilities, and assessing, identifying, and managing risks from cybersecurity threats, including identifying and responding to cybersecurity incidents, and processes for 2023 Annual Report 49 categorizing incidents, reporting findings, and keeping senior management, our Audit Committee, and other key stakeholders informed and involved as appropriate.
These plans outline a coordinated approach for protecting information security, managing vulnerabilities, and assessing, identifying, and managing risks from cybersecurity threats, including 2024 Annual Report 49 identifying and responding to cybersecurity incidents, and processes for categorizing incidents, reporting findings, and keeping senior management, our Audit Committee, and other key stakeholders informed and involved as appropriate.
A number of internal teams, including our Operations Infrastructure Team, Operations End User Computer Team, Operations Engineering Team, Security, Risk and Compliance Team, Operational Technology Team, and Application Administrators and certain external vendors (together, the Incident Response Team Members ), collectively with the IMT, form the Incident Response Team ( IRT ), which investigates and responds to privacy or cybersecurity incidents.
Internal teams, including our Operations Infrastructure Team, Operations End User Computer Team, Operations Engineering Team, Security, Risk and Compliance Team, Operational Technology Team, and Application Administrators and certain external vendors (together, the Incident Response Team Members ), collectively with the IMT, form the Incident Response Team ( IRT ), which investigates and responds to privacy or cybersecurity incidents.
We do not have reason to believe that risks from cybersecurity threats, including as a result of any previous cybersecurity incidents, are reasonably likely to materially affect our business, reputation, operations, or revenue over the long term.
However, we do not have reason to believe that risks from cybersecurity threats, including as a result of any previous cybersecurity incidents, are reasonably likely to materially affect our business, reputation, operations, or revenue over the long term. 50 United Therapeutics, a public benefit corporation
Our SRC Director has technical leadership experience and cybersecurity expertise gained from over 25 years of experience, including security leadership, program development, strategy formulation, data protection, and IT risk management within the health care, pharmaceutical, and biotechnology industries. The security professionals in the IMT have cybersecurity backgrounds and expertise relevant to their roles, including, in certain circumstances, relevant industry certifications.
Our SRC Director has technical leadership experience and cybersecurity expertise gained from over 25 years of experience, including security leadership, program development, strategy formulation, data protection, and IT risk management within the health care, pharmaceutical, and biotechnology industries.
Management At the management level, our Corporate Crisis Management Team ( CCMT ) is comprised of senior representatives from all key business functions, including finance, operations, and legal, and has broad oversight of our risk management processes. The CCMT has global responsibility for corporate crisis management, policy guidance, and training for employees involved in crisis management at all levels.
Management At the management level, our Corporate Crisis Management Team ( CCMT ) is comprised of senior representatives from all key business functions, including finance, operations, and legal, and has broad oversight of our risk management processes, including management of cybersecurity risks.
We have protocols by which the IMT escalates certain cybersecurity incidents within our Company and, where appropriate, the IMT will notify appropriate stakeholders and our Audit Committee and provide updates on the status of the incident.
We have protocols by which the IMT escalates certain cybersecurity incidents within our company and, where appropriate, the IMT will notify appropriate stakeholders and our Audit Committee and provide updates on the status of the incident. Experienced employees responsible for various parts of our business and a team of trained cybersecurity professionals assist our SRC Director and the IMT.
Additional information on cybersecurity risks we face is discussed in Part I, Item 1A—Risk Factors , which should be read in conjunction with this Item 1C—Cybersecurity .
The CCMT has global responsibility for corporate crisis management, policy guidance, and training for employees involved in crisis management at all levels. Additional information on cybersecurity risks we face is discussed in Part I, Item 1A—Risk Factors , which should be read in conjunction with this Item 1C—Cybersecurity .
Risk Management and Strategy We manage cybersecurity risks through a robust enterprise risk management process. These policies and practices follow the National Institute of Standards and Technology ( NIST ) cybersecurity framework.
We have implemented a risk-based approach to identify and assess the cybersecurity threats that could affect our business and information systems, and we manage cybersecurity risks through a robust enterprise risk management process. These policies and practices are aligned with industry best practices and standards, such as the National Institute of Standards and Technology ( NIST ) cybersecurity framework.
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Governance Board of Directors Our board of directors has delegated the primary responsibility to oversee risks related to cybersecurity matters to our Audit Committee.
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Our Chief Information Officer has nearly ten years of experience with our company, and an extensive background in security technology and operations, compliance, data privacy, business continuity, and disaster recovery. The security professionals in the IMT have cybersecurity backgrounds and expertise relevant to their roles, including, in certain circumstances, relevant industry certifications.
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A number of experienced employees responsible for various parts of our business and a team of trained cybersecurity professionals assist our SRC Director and the IMT.
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Risk Management and Strategy We operate in the biotechnology sector, which is subject to various cybersecurity risks that could adversely impact our business, financial condition, and results of operations, including intellectual property theft; fraud; extortion; harm to employees, patients, or healthcare providers; violation of privacy laws and other litigation and legal risk; and reputational risk.
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Our business depends on the availability, reliability, and security of our information systems, networks, data, and intellectual property.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeIn 2023, we demolished a 47,000 square foot administrative building near 50 United Therapeutics, a public benefit corporation the RTP facility and have commenced construction of a new Tyvaso DPI manufacturing facility on this site.
Biggest changeWe lease approximately 21,000 square feet of office space in Morrisville, North Carolina to house representatives from our United Therapeutics Cares patient support program. In 2023, we demolished a 47,000 square foot administrative building near the RTP facility and have commenced construction of a new Tyvaso DPI manufacturing facility on this site.
We manufacture Orenitram drug product and we package, warehouse, and distribute nebulized Tyvaso, Remodulin, Orenitram, and Unituxin at this location.
We manufacture Orenitram drug product and we package, warehouse, and distribute nebulized Tyvaso, Tyvaso DPI, Remodulin, Orenitram, and Unituxin at this location.
We also own a 170-acre site containing approximately 225,000 square feet of building space adjacent to our RTP facility, which we use for our research, development, warehousing and logistics hub and manufacturing facilities related to our lung regeneration program, office space, and for future expansion.
We also own a 170-acre site containing approximately 225,000 square feet of building space in RTP, which we use for our research, development, warehousing and logistics hub and manufacturing facilities related to our lung regeneration program, office space, and for future expansion.
Item 2. Properties Maryland—We own a 415,000 square foot combination laboratory and office building campus in Silver Spring, Maryland that serves as our co-headquarters, is used to manufacture our products, and houses one of our ex vivo lung perfusion centers.
Maryland—We own a 415,000 square foot combination laboratory and office building campus in Silver Spring, Maryland that serves as our co-headquarters, is used to manufacture our products, and houses one of our ex vivo lung perfusion centers.
We also plan to produce manufactured lungs for clinical studies at our Silver Spring campus. North Carolina—We own a 380,000 square foot combination manufacturing facility and office building in Research Triangle Park, North Carolina ( RTP facility ), which serves as our co-headquarters and is occupied by our clinical research and development, commercialization, and our logistics and manufacturing personnel.
Item 2. Properties North Carolina—We own a 380,000 square foot combination manufacturing facility and office building in Research Triangle Park, North Carolina ( RTP ), which serves as our co-headquarters and is occupied by our clinical research and development, commercialization, and logistics and manufacturing personnel.
We also lease a laboratory and farm in southwestern Virginia that support our xenotransplantation research and development efforts. Minnesota—Our Miromatrix subsidiary leases a 42,300 square foot office and laboratory facility in Eden Prairie, Minnesota, where it produces manufactured kidney and liver products for research and development purposes and clinical trials.
We also plan to produce manufactured lung alternatives for clinical studies at our Silver Spring campus. Minnesota—Our Miromatrix subsidiary leases a 42,300 square foot office and laboratory facility in Eden Prairie, Minnesota, where it produces manufactured kidney and liver products for research and development purposes and clinical trials.
Additionally, in 2023, we completed construction of a new warehouse and logistics hub near our RTP facility to serve as the storage and distribution facility for Tyvaso DPI. Virginia—We recently completed a 65,000 square foot designated pathogen-free facility in southwestern Virginia intended to produce porcine hearts and kidneys for use in xenotransplantation clinical trials.
Additionally, in 2023, we completed construction of a new warehouse and logistics hub near our RTP facility to serve as the storage and distribution facility for Tyvaso DPI.
New Hampshire—We lease a 74,500 square foot office and laboratory facility in Manchester, New Hampshire, where we conduct our 3-D organ bioprinting research and development activities. We believe that these facilities, along with various other owned and leased facilities, are adequate for our current operations and that additional land and facilities for future expansion are reasonably available.
Quebec—We own a 23,000 square foot facility in Bromont, Quebec, Canada, which is dedicated to the development of sustainable aircraft for the delivery of manufactured organs and organ alternatives. We believe that these facilities, along with various other owned and leased facilities, are adequate for our current operations and that additional land and facilities for future expansion are reasonably available.
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We recently commenced construction of a 55,000 square foot clinical-scale designated pathogen-free ( DPF ) facility in Stewartville, Minnesota intended to produce porcine hearts and kidneys for use in xenotransplantation clinical trials, and to support eventual commercial production of our xeno-organs following FDA approval.
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Florida—We own a 75,000 square foot building on land we lease on the Mayo Clinic campus in Jacksonville, Florida, which houses one of our ex vivo lung perfusion centers. We also own a 14,000 square foot building in Melbourne, Florida, which houses a call center.
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New Hampshire—We lease a 74,500 square foot office and laboratory facility in Manchester, New Hampshire, where we conduct our 3D organ alternative bioprinting research and development activities.
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Texas—We have entered into an agreement to acquire 22 acres of land in Houston, Texas, where we intend to construct a clinical scale DPF facility intended to produce porcine hearts and kidneys for use in xenotransplantation clinical trials, and to support eventual commercial production of our xeno-organs following FDA approval.
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Virginia—We own and operate a 65,000 square foot clinical-scale DPF facility in Christiansburg, Virginia intended to produce porcine hearts and kidneys for use in xenotransplantation clinical trials, and to support eventual commercial production of our xeno-organs following FDA approval. We also lease a laboratory and farm in Blacksburg, Virginia that support our xenotransplantation research and development efforts.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeSee Note 14— Litigation , to our consolidated financial statements, which is incorporated herein by reference. Item 4. Mine Safety Disclosures Not applicable. PART II
Biggest changeSee Note 14— Litigation , to our consolidated financial statements, which is incorporated herein by reference. Item 4. Mine Safety Disclosures Not applicable. 2024 Annual Report 51 PART II
While we presently believe that the ultimate outcome of these proceedings, individually and in the aggregate, will not materially harm our financial position, cash flows or results of operations, legal proceedings are inherently uncertain, and unfavorable rulings could, individually or in aggregate, have a material adverse effect on our business, financial condition, or operating results.
While we presently believe that the ultimate outcome of these proceedings, individually and in the aggregate, will not materially harm our financial position, cash flows, or results of operations, legal proceedings are inherently uncertain, and unfavorable rulings could, individually or in the aggregate, have a material adverse effect on our business, financial condition, or operating results.

Item 4. Mine Safety Disclosures

Mine Safety Disclosures — required of mining issuers

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Biggest changeItem 4. Mine Safety Disclosures 51 PART II 51 Item 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 51 Item 6. [Reserved] 52 Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations 53 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 64 Item 8.
Biggest changeItem 4. Mine Safety Disclosures 51 PART II 52 Item 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 52 Item 6. [Reserved] 53 Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations 54 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 65 Item 8.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeIssuer Purchases of Equity Securities We did not repurchase any of our outstanding equity securities during the year ended December 31, 2023. 2023 Annual Report 51 Comparison of Five-Year Total Cumulative Shareholder Return The following chart shows the performance from December 31, 2018 through December 31, 2023 of our common stock, compared with an investment in the stocks represented in each of the Nasdaq U.S.
Biggest changeIssuer Purchases of Equity Securities We did not repurchase any of our outstanding equity securities during the three months ended December 31, 2024, as our most recent share repurchase program was completed in September 2024. 52 United Therapeutics, a public benefit corporation Comparison of Five-Year Total Cumulative Shareholder Return The following chart shows the performance from December 31, 2019 through December 31, 2024 of our common stock, compared with an investment in the stocks represented in each of the Nasdaq U.S.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock trades on the Nasdaq Global Select Market under the symbol “UTHR”. Number of Holders As of February 14, 2024, there were 31 holders of record of our common stock.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock trades on the Nasdaq Global Select Market under the symbol “UTHR”. Number of Holders As of February 19, 2025, there were 26 holders of record of our common stock.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeThe tables below include a reconciliation of the liability accounts associated with these deductions (in millions): 2023 Annual Report 57 Year Ended December 31, 2023 Rebates & Chargebacks Prompt Pay Discounts Allowance for Sales Returns Distributor Fees Total Balance, January 1, 2023 $ 81.3 $ 4.4 $ 3.3 $ 10.9 $ 99.9 Provisions attributed to sales in: Current period 278.0 52.5 1.3 40.7 372.5 Prior periods (2.5) (0.1) (1.9) (0.9) (5.4) Payments or credits attributed to sales in: Current period (169.8) (47.3) — (30.3) (247.4) Prior periods (78.6) (4.2) (0.8) (10.0) (93.6) Balance, December 31, 2023 $ 108.4 $ 5.3 $ 1.9 $ 10.4 $ 126.0 Year Ended December 31, 2022 Rebates & Chargebacks Prompt Pay Discounts Allowance for Sales Returns Distributor Fees Total Balance, January 1, 2022 $ 67.8 $ 3.8 $ 6.3 $ 7.9 $ 85.8 Provisions attributed to sales in: Current period 202.8 43.2 2.3 34.5 282.8 Prior periods (4.3) (0.5) (3.1) 0.5 (7.4) Payments or credits attributed to sales in: Current period (121.1) (38.9) (0.7) (23.6) (184.3) Prior periods (63.9) (3.2) (1.5) (8.4) (77.0) Balance, December 31, 2022 $ 81.3 $ 4.4 $ 3.3 $ 10.9 $ 99.9 Year Ended December 31, 2021 Rebates & Chargebacks Prompt Pay Discounts Allowance for Sales Returns Distributor Fees Total Balance, January 1, 2021 $ 65.3 $ 3.0 $ 12.5 $ 3.7 $ 84.5 Provisions attributed to sales in: Current period 217.0 38.5 — 31.3 286.8 Prior periods 1.6 — (3.9) 0.2 (2.1) Payments or credits attributed to sales in: Current period (151.8) (34.7) — (22.4) (208.9) Prior periods (64.3) (3.0) (2.3) (4.9) (74.5) Balance, December 31, 2021 $ 67.8 $ 3.8 $ 6.3 $ 7.9 $ 85.8 Cost of Sales The table below summarizes cost of sales by major category (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2023 2022 2021 2023 v. 2022 2022 v. 2021 2023 v. 2022 2022 v. 2021 Category: Cost of sales $ 255.1 $ 146.7 $ 116.7 $ 108.4 $ 30.0 74 % 26 % Share-based compensation expense (1) 2.4 4.9 5.8 (2.5) (0.9) (51) % (16) % Total cost of sales $ 257.5 $ 151.6 $ 122.5 $ 105.9 $ 29.1 70 % 24 % (1) See Share-Based Compensation section below for discussion.
Biggest changeThe tables below present a reconciliation of the liability accounts associated with these deductions (in millions): Year Ended December 31, 2024 Rebates & Chargebacks Prompt Pay Discounts Allowance for Sales Returns Distributor Fees Total Balance, January 1, 2024 $ 108.4 $ 5.3 $ 1.9 $ 10.4 $ 126.0 Provisions attributed to sales in: Current period 356.0 64.4 1.9 41.8 464.1 Prior periods (10.6) — (1.0) (0.9) (12.5) Payments or credits attributed to sales in: Current period (215.8) (59.3) — (30.4) (305.5) Prior periods (97.2) (5.3) (0.6) (9.3) (112.4) Balance, December 31, 2024 $ 140.8 $ 5.1 $ 2.2 $ 11.6 $ 159.7 Year Ended December 31, 2023 Rebates & Chargebacks Prompt Pay Discounts Allowance for Sales Returns Distributor Fees Total Balance, January 1, 2023 $ 81.3 $ 4.4 $ 3.3 $ 10.9 $ 99.9 Provisions attributed to sales in: Current period 278.0 52.5 1.3 40.7 372.5 Prior periods (2.5) (0.1) (1.9) (0.9) (5.4) Payments or credits attributed to sales in: Current period (169.8) (47.3) — (30.3) (247.4) Prior periods (78.6) (4.2) (0.8) (10.0) (93.6) Balance, December 31, 2023 $ 108.4 $ 5.3 $ 1.9 $ 10.4 $ 126.0 2024 Annual Report 59 Year Ended December 31, 2022 Rebates & Chargebacks Prompt Pay Discounts Allowance for Sales Returns Distributor Fees Total Balance, January 1, 2022 $ 67.8 $ 3.8 $ 6.3 $ 7.9 $ 85.8 Provisions attributed to sales in: Current period 202.8 43.2 2.3 34.5 282.8 Prior periods (4.3) (0.5) (3.1) 0.5 (7.4) Payments or credits attributed to sales in: Current period (121.1) (38.9) (0.7) (23.6) (184.3) Prior periods (63.9) (3.2) (1.5) (8.4) (77.0) Balance, December 31, 2022 $ 81.3 $ 4.4 $ 3.3 $ 10.9 $ 99.9 Cost of Sales The table below summarizes cost of sales by major category (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2024 2023 2022 2024 v. 2023 2023 v. 2022 2024 v. 2023 2023 v. 2022 Category: Cost of sales $ 304.3 $ 255.1 $ 146.7 $ 49.2 $ 108.4 19 % 74 % Share-based compensation expense (1) 5.4 2.4 4.9 3.0 (2.5) 125 % (51) % Total cost of sales $ 309.7 $ 257.5 $ 151.6 $ 52.2 $ 105.9 20 % 70 % (1) See Share-Based Compensation section below for discussion.
Obligations Under License Agreements and Acquisition Agreements We pay a ten percent royalty on our net sales of Tyvaso DPI under our license agreement with MannKind. Under our agreement with Arena, we will owe a low double-digit, tiered royalty on net product sales of ralinepag (any route of administration), plus certain milestone payments upon defined regulatory events.
Obligations Under License Agreements and Acquisition Agreements We pay a ten percent royalty on our net sales of Tyvaso DPI under our license agreement with MannKind. Under our agreement with Arena, we will owe a low double-digit, tiered royalty on net product sales of ralinepag (for any route of administration), plus certain milestone payments upon defined regulatory events.
Unsecured Revolving Credit Facilities In March 2022, we entered into the 2022 Credit Agreement, which provides for unsecured revolving credit facilities of up to $2.0 billion in the aggregate. On March 31, 2022, we borrowed $800.0 million under the facilities and used the funds to repay outstanding indebtedness under our then-existing credit agreement (the 2018 Credit Agreement ).
Unsecured Revolving Credit Facilities In March 2022, we entered into the 2022 Credit Agreement, which provides for unsecured revolving credit facilities of up to $2.0 billion in the aggregate. On March 31, 2022, we borrowed $800.0 million under the facilities and used the funds to repay outstanding indebtedness under our then-existing credit agreement.
Our ability to achieve our objectives, grow our business, and maintain profitability will depend on many factors, including among others: (1) the timing and outcome of preclinical research, clinical trials, and regulatory approval applications for products we develop; (2) the timing and degree of our success in commercially launching new products; (3) the demand for our products; (4) the price of our products and the reimbursement of our products by public and private health insurance organizations, including the impact on such prices and reimbursement amounts as a result of the IRA; (5) the competition we face within our industry, including competition from generic companies and the anticipated launch of new PAH and PH-ILD therapies; (6) our ability to effectively manage our business in an increasingly complex legal and regulatory environment; (7) our ability to defend against challenges to our patents; and (8) the risks identified in Part I, Item 1A—Risk Factors , included in this Report.
Our ability to achieve our objectives, grow our business, and maintain profitability will depend on many factors, including among others: (1) the timing and outcome of preclinical research, clinical trials, and regulatory approval applications for products we develop; (2) the timing and degree of our success in commercially launching new products; (3) the demand for our products; (4) the net price of our products and the reimbursement of our products by public and private health insurance organizations, including the impact on such net prices and reimbursement amounts as a result of the IRA, and as a result of additional payer rebates; (5) the competition we face within our industry, including competition from generic companies and the anticipated launch of new PAH and PH-ILD therapies; (6) our ability to effectively manage our business in an increasingly complex legal and regulatory environment; (7) our ability to defend against challenges to our patents; and (8) the risks identified in Part I, Item 1A—Risk Factors , included in this Report.
We do not have any other off-balance sheet arrangements within the meaning of Item 303(a)(4) of Regulation S-K. 62 United Therapeutics, a public benefit corporation Summary of Critical Accounting Policies and Estimates We prepare our consolidated financial statements in conformity with generally accepted accounting principles in the United States ( GAAP ).
We do not have any other off-balance sheet arrangements within the meaning of Item 303(a)(4) of Regulation S-K. 64 United Therapeutics, a public benefit corporation Summary of Critical Accounting Policies and Estimates We prepare our consolidated financial statements in conformity with generally accepted accounting principles in the United States ( GAAP ).
See Note 12— Commitments and Contingencies to our consolidated financial statements for further details. In addition, we may owe additional earn-out consideration to the former securityholders of IVIVA and Miromatrix, as described in Note 16— Acquisitions to our consolidated financial statements. Off-Balance Sheet Arrangements We hold an interest in an unconsolidated variable interest entity ( VIE ).
See Note 12— Commitments and Contingencies to our consolidated financial statements for further details. In addition, we may owe additional earn-out consideration to the former securityholders of IVIVA and Miromatrix, as described in Note 15 — Acquisitions to our consolidated financial statements. Off-Balance Sheet Arrangements We hold an interest in an unconsolidated variable interest entity ( VIE ).
Provisions attributed to sales in prior periods have been less than one percent of our total revenues for each of the years ended December 31, 2023, 2022, and 2021. For a roll-forward of the liability accounts associated with our gross-to-net deductions, see the section above entitled Results of Operations—Gross-to-Net Deductions .
Provisions attributed to sales in prior periods have been less than one percent of our total revenues for each of the years ended December 31, 2024, 2023, and 2022. For a roll-forward of the liability accounts associated with our gross-to-net deductions, see the section above entitled Results of Operations—Gross-to-Net Deductions .
During the year ended December 31, 2023, we recorded $46.0 million in IPR&D expense in connection with the acquisition of IVIVA Medical, Inc. ( IVIVA ). (6) Calculation is not meaningful. Research and development, excluding share-based compensation.
During the year ended December 31, 2023, we recorded $46.0 million in IPR&D expense in connection with the acquisition of IVIVA Medical, Inc. ( IVIVA ). (5) Calculation is not meaningful. Research and development, excluding share-based compensation.
(4) Purchase obligations primarily include: (1) commitments related to research and development (including clinical trials) for new and existing products; (2) open purchase orders for capital expenditures primarily related to our continued investment in construction of additional facilities to support the development and commercialization of our products and technologies; and (3) open purchase orders for the acquisition of goods and services in the ordinary course of business.
(4) Purchase obligations primarily include: commitments related to research and development (including clinical trials) for new and existing products; open purchase orders for capital expenditures primarily related to our continued investment in construction of additional facilities to support the development and commercialization of our products and technologies; and open purchase orders for the acquisition of goods and services in the ordinary course of business.
The increase in sales and marketing expense for the year ended December 31, 2023, as compared to the same period in 2022, was primarily due to increases in: (1) personnel expense due to growth in headcount; and (2) consulting expenses.
The increase in sales and marketing expense for the year ended December 31, 2024, as compared to the same period in 2023, was primarily due to increases in: (1) personnel expense due to growth in headcount; (2) marketing expenses; and (3) consulting expenses.
Discussions of year-to-year comparisons between 2022 and 2021 that are not included in this Report can be found in Part II, Item 7—Management’s Discussion and Analysis of Financial Condition and Results of Operations—Results of Operations of our Form 10-K filed on February 22, 2023 (our 2022 Annual Report ).
Discussions of year-to-year comparisons between 2023 and 2022 that are not included in this Report can be found in Part II, Item 7—Management’s Discussion and Analysis of Financial Condition and Results of Operations—Results of Operations of our Form 10-K filed on February 21, 2024 (our 2023 Annual Report ).
See Note 12— Commitments and Contingencies to our consolidated financial statements for further details. (6) As of December 31, 2023, our other non-current liabilities in our consolidated balance sheets includes a liability of $7.0 million for unrecognized tax benefits, including related interest and penalties.
See Note 12— Commitments and Contingencies to our consolidated financial statements for further details. (6) As of December 31, 2024, our other non-current liabilities in our consolidated balance sheets includes a liability of $20.0 million for unrecognized tax benefits, including related interest and penalties.
See Note 8 —Share-Based Compensation , to our consolidated financial statements for more information. Other (Expense) Income, Net The change in other (expense) income, net for the year ended December 31, 2023, as compared to the same period in 2022, was primarily due to net unrealized and realized gains and losses on equity securities.
See Note 8 —Share-Based Compensation , to our consolidated financial statements for more information. Other Income (Expense), Net The change in other income (expense), net for the year ended December 31, 2024, as compared to the same period in 2023, was primarily due to net unrealized gains on equity securities.
Selling, General, and Administrative Our selling, general, and administrative expenses primarily include costs associated with the commercialization of approved products and general and administrative costs to support our operations. Selling expenses also include share-based compensation, salary-related expenses, product marketing and sales operations costs, and other costs incurred to support our sales efforts.
Selling, General, and Administrative Our selling, general, and administrative expenses primarily include costs associated with the commercialization of approved products and general and administrative costs to support our operations, including share-based compensation and salary-related expenses. Selling expenses include product marketing and sales operations costs, as well as other costs incurred to support our sales efforts.
These statements, which are based on our beliefs and expectations about future outcomes and on information available to us through the date this Report on Form 10-K is filed with the SEC, include, among others, statements related to the following: • Expectations of revenues, expenses, profitability, cash flows, and growth in the number of patients being treated with our products, including anticipated growth in the number of nebulized Tyvaso patients as a result of the expansion of its label to include pulmonary hypertension associated with interstitial lung disease ( PH-ILD ) and anticipated growth in Tyvaso DPI revenues; • The sufficiency of our cash on hand to support operations; • Our ability to obtain and maintain domestic and international regulatory approvals; • Our ability to maintain attractive pricing and reimbursement levels for our products, in light of increasing competition, including from generic products and pressure from government and other payers to decrease the costs associated with healthcare, including the potential impact of the Inflation Reduction Act of 2022 ( IRA ) on our business; • The expected volume and timing of sales of our commercial products, as well as potential future commercial products, including the anticipated effect of various research and development efforts on sales of these products; • The timing and outcome of clinical studies, other research and development efforts, and related regulatory filings and approval s; • The outcome of pending and potential future legal and regulatory actions by the U.S.
These statements, which are based on our beliefs and expectations about future outcomes and on information available to us through the date this Report on Form 10-K is filed with the SEC, include, among others, statements related to the following: • Expectations of revenues, expenses, profitability, cash flows, and growth in the number of patients being treated with our products, including continued growth in sales of our newest product, Tyvaso DPI, and anticipated growth in the number of patients with pulmonary hypertension associated with interstitial lung disease ( PH-ILD ) being treated with our Tyvaso products; • The sufficiency of our cash on hand to support operations; • Our ability to obtain and maintain domestic and international regulatory approvals; • Our ability to maintain attractive pricing and reimbursement levels for our products, in light of increasing competition, including from generic products, and pressure from government and other payers to decrease the costs associated with healthcare, including the potential impact of the Inflation Reduction Act of 2022 ( IRA ) on our business; • The anticipated impact our rebate agreements with pharmacy benefit managers will have on our net revenues; • The expected volume and timing of sales of our commercial products, as well as potential future commercial products, including the anticipated effect of various research and development efforts on sales of these products; • The timing and outcome of clinical studies, other research and development efforts, and related regulatory filings and approval s; • The outcome of pending and potential future legal and regulatory actions by the U.S.
In addition, there are a number of investigational products in late-stage development that, if approved, may erode the market share of our existing commercial therapies and make market acceptance more difficult to achieve for any therapies we attempt to market in the future.
In addition, there are investigational products in late-stage development that, if approved, may erode the market share or net prices of our existing commercial therapies and make market acceptance more difficult to achieve for any therapies we attempt to market in the future.
Although we no longer grant STAP awards, we had approximat ely 0 .4 million STAP awards outstanding as of December 31, 2023. We account for STAP awards as liabilities because they are settled in cash.
Although we no longer grant STAP awards, we had approximat ely 0 .1 million STAP awards outstanding as of December 31, 2024. We account for STAP awards as liabilities because they are settled in cash.
Currently, we grant stock options and restricted stock units under the United Therapeutics Corporation Amended and Restated 2015 Stock Incentive Plan (as amended to date, the 2015 Plan ), which provides for the issuance of up to 12,500,000 shares of our common stock, including the 1,000,000 shares added pursuant to an amendment and restatement of the 2015 Plan approved by our shareholders in June 2023.
Currently, we grant stock options and restricted stock units under the United Therapeutics Corporation Amended and Restated 2015 Stock Incentive Plan (as amended to date, the 2015 Plan ), which provides for the issuance of up to 13,820,000 shares of our common stock, including the 1,320,000 shares added pursuant to an amendment and restatement of the 2015 Plan approved by our shareholders in June 2024.
Nebulized Tyvaso was also approved by the FDA in March 2021 and by regulators in Israel in December 2022 to improve exercise ability in patients with PH-ILD.
Nebulized Tyvaso was also approved by the FDA in March 2021 and by regulators in Israel and Japan in December 2022 and September 2024, respectively, to improve exercise ability in patients with PH-ILD.
For additional detail regarding our research and development programs, see Part I, Item 1 — Business — Research and Development. Revenues Our total revenues consist primarily of sales of the commercial products noted above, together with associated sales of administration devices (in the case of Tyvaso DPI, nebulized Tyvaso, and Remodulin).
For additional detail regarding our research and development programs, see Part I, Item 1 — Business — Research and Development. Revenues Our total revenues consist primarily of sales of the commercial products noted above, including the delivery devices (in the case of Tyvaso DPI, nebulized Tyvaso, and Remodulin).
See Note 4 —Investments and Note 5— Fair Value Measurements, to our consolidated financial statements for more information. Income Tax Expense Income tax expense was $289.5 million for the year ended December 31, 2023, compared to $223.3 million for the same period in 2022.
See Note 4 —Investments and Note 5— Fair Value Measurements, to our consolidated financial statements for more information. Income Tax Expense Income tax expense was $343.9 million for the year ended December 31, 2024, compared to $289.5 million for the same period in 2023.
Due to this time lag, we must estimate the amount of rebates and chargebacks to accrue. As of December 31, 2023 and 2022, we had a liability of $108.4 million and $81.3 million, respectively, related to rebates and chargebacks.
Due to this time lag, we must estimate the amount of rebates and chargebacks to accrue. As of December 31, 2024 and 2023, we had a liability of $140.8 million and $108.4 million, respectively, related to rebates and chargebacks.
The information we have about patient demand, the number of patients using our products, and inventory held by our distributors is based upon our review of patient utilization and inventory data provided to us by our specialty pharmaceutical distributors. 54 United Therapeutics, a public benefit corporation Operating Expenses We devote substantial resources to our various clinical trials and other research and development efforts, which are conducted both internally and through third parties.
The information we have about patient demand, the number of patients using our products, and inventory held by our distributors, is based upon our review of patient utilization and inventory data provided to us by our specialty pharmaceutical distributors. 2024 Annual Report 55 Operating Expenses We devote substantial resources to our various clinical trials and other research and development efforts, which are conducted both internally and through third parties.
Although our credit facility matures in 2028, we reclassified $400.0 million of the outstanding balance as a current liability on our consolidated balance sheet as of December 31, 2023 as we intend to repay this amount within one year. See Unsecured Revolving Credit Facilities below for further details.
Although our credit facility matures in 2029, we reclassified the outstanding balance of $300.0 million as a current liability in our consolidated balance sheets as of December 31, 2024, as we intend to repay this amount within one year. See Unsecured Revolving Credit Facilities below for further details.
Unituxin net product sales increased in 2023, as compared to 2022, primarily due to a price increase. The table below presents the breakdown of total revenues between the United States and rest-of-world ( ROW ) (in millions): Year Ended December 31, 2023 2022 2021 U.S. ROW Total U.S. ROW Total U.S.
Unituxin net product sales increased in 2024, as compared to 2023, primarily due to a price increase and an increase in quantities sold. 58 United Therapeutics, a public benefit corporation The table below presents the breakdown of total revenues between the United States and rest-of-world ( ROW ) (in millions): Year Ended December 31, 2024 2023 2022 U.S.
We paid down $100.0 million of our balance under the 2022 Credit Agreement during the year ended December 31, 2023. The aggregate balance of $700.0 million under our 2022 Credit Agreement remained outstanding as of both December 31, 2023 and February 21, 2024.
We paid down $400.0 million of our balance under the 2022 Credit Agreement during the year ended December 31, 2024. The aggregate balance of $300.0 million under our 2022 Credit Agreement remained outstanding as of both December 31, 2024 and February 26, 2025.
See Note 7— Debt to our consolidated financial statements for further details. (2) Estimated based on the intrinsic value of exercisable outstanding STAP awards as of December 31, 2023. See Note 8 —Share-Based Compensation—STAP Awards to our consolidated financial statements for further details. (3) Consists of actuarially derived, undiscounted, estimated future payouts of benefits.
(2) Estimated based on the intrinsic value of exercisable outstanding STAP awards as of December 31, 2024. See Note 8 —Share-Based Compensation—STAP Awards to our consolidated financial statements for further details. (3) Consists of actuarially derived, undiscounted, estimated future payouts of benefits. See Note 11— Employee Benefit Plans—Supplemental Executive Retirement Plan to our consolidated financial statements for further details.
Share-Based Compensation The table below summarizes share-based compensation expense by major category (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2023 2022 2021 2023 v. 2022 2022 v. 2021 2023 v. 2022 2022 v. 2021 Category: Stock options $ 15.4 $ 22.6 $ 25.4 $ (7.2) $ (2.8) (32) % (11) % Restricted stock units 52.4 35.7 24.7 16.7 11.0 47 % 45 % STAP awards (30.7) 46.7 86.6 (77.4) (39.9) (166) % (46) % Employee stock purchase plan 2.0 1.8 1.8 0.2 — 11 % — % Total share-based compensation expense $ 39.1 $ 106.8 $ 138.5 $ (67.7) $ (31.7) (63) % (23) % The table below summarizes share-based compensation expense by line item in our consolidated statements of operations (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2023 2022 2021 2023 v. 2022 2022 v. 2021 2023 v. 2022 2022 v. 2021 Cost of sales $ 2.4 $ 4.9 $ 5.8 $ (2.5) $ (0.9) (51) % (16) % Research and development 15.6 23.8 24.4 (8.2) (0.6) (34) % (2) % Selling, general, and administrative 21.1 78.1 108.3 (57.0) (30.2) (73) % (28) % Total share-based compensation expense $ 39.1 $ 106.8 $ 138.5 $ (67.7) $ (31.7) (63) % (23) % The decrease in share-based compensation expense for the year ended December 31, 2023, as compared to the same period in 2022, was primarily due to: (1) an increase in STAP benefit driven by a 21 percent decrease in our stock price during 2023, as compared to a 29 percent increase in our stock price during 2022; and (2) a decrease in stock option expense due to fewer awards remaining outstanding in 2023, as compared to the same period in 2022, partially offset by an increase in restricted stock unit expense.
Share-Based Compensation The table below summarizes share-based compensation expense by major category (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2024 2023 2022 2024 v. 2023 2023 v. 2022 2024 v. 2023 2023 v. 2022 Category: Stock options $ 29.8 $ 15.4 $ 22.6 $ 14.4 $ (7.2) 94 % (32) % Restricted stock units 79.7 52.4 35.7 27.3 16.7 52 % 47 % STAP awards 32.3 (30.7) 46.7 63.0 (77.4) 205 % (166) % Employee stock purchase plan 2.2 2.0 1.8 0.2 0.2 10 % 11 % Total share-based compensation expense $ 144.0 $ 39.1 $ 106.8 $ 104.9 $ (67.7) 268 % (63) % 2024 Annual Report 61 The table below summarizes share-based compensation expense by line item in our consolidated statements of operations (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2024 2023 2022 2024 v. 2023 2023 v. 2022 2024 v. 2023 2023 v. 2022 Cost of sales $ 5.4 $ 2.4 $ 4.9 $ 3.0 $ (2.5) 125 % (51) % Research and development 29.1 15.6 23.8 13.5 (8.2) 87 % (34) % Selling, general, and administrative 109.5 21.1 78.1 88.4 (57.0) 419 % (73) % Total share-based compensation expense $ 144.0 $ 39.1 $ 106.8 $ 104.9 $ (67.7) 268 % (63) % The increase in share-based compensation expense for the year ended December 31, 2024, as compared to the same period in 2023, was primarily due to: (1) an increase in STAP expense driven by a 60 percent increase in our stock price during 2024, as compared to a 21 percent decrease in our stock price during 2023; (2) an increase in restricted stock unit expense due to a greater number of awards granted and remaining outstanding in 2024, as compared to the same period in 2023; and (3) an increase in stock option expense due to a greater number of awards granted in 2024, as compared to the same period in 2023.
The following factors, among others, have a significant impact on the amount of share-based compensation expense (benefit) recognized in connection with STAP awards from period to period: (1) volatility in the price of our common stock (specifically, increases in the price of our common stock will generally result in an increase in our liability and related compensation expense, while decreases in our stock price will generally result in a reduction in our liability and related compensation expense); and (2) decreases in the number of outstanding awards. 2023 Annual Report 55 Future Prospects We anticipate that overall revenue growth over the near-term will be driven primarily by: (1) growth in sales of the recently-launched Tyvaso DPI, and growth in sales of nebulized Tyvaso as a result of the expansion of its label to include PH-ILD; (2) continued growth in the number of patients prescribed Orenitram following our expansion of the Orenitram label to reflect the results of the FREEDOM-EV study; and (3) modest price increases for some of our products.
The following factors, among others, impact the amount of share-based compensation expense (benefit) recognized in connection with STAP awards from period to period: (1) volatility in the price of our common stock (specifically, increases in the price of our common stock will generally result in an increase in our liability and related compensation expense, while decreases in our stock price will generally result in a reduction in our liability and related compensation expense); and (2) decreases in the number of outstanding awards. 56 United Therapeutics, a public benefit corporation Future Prospects We anticipate that revenue growth over the near-term will be driven primarily by: (1) continued growth in sales of Tyvaso DPI; (2) continued growth in the number of PH-ILD patients prescribed Tyvaso DPI and nebulized Tyvaso; (3) continued growth in the number of patients prescribed Orenitram; and (4) modest price increases for some of our products.
For example, if Yutrepia is commercially launched, our Tyvaso revenues could potentially be materially adversely affected, and the impact may be more material if Yutrepia is approved for the treatment of PH-ILD. Results of Operations This section of this Report generally discusses 2023, 2022, and 2021 items and year-to-year comparisons between 2023 and 2022.
If Yutrepia receives final approval and is commercially launched, our revenues from Tyvaso DPI could be materially adversely affected, and the impact may be greater if Yutrepia is ultimately approved for the treatment of PH-ILD. 2024 Annual Report 57 Results of Operations This section of this Report generally discusses 2024, 2023, and 2022 items and year-to-year comparisons between 2024 and 2023.
ROW Total Net product sales: Tyvaso DPI (1) $ 731.1 $ — $ 731.1 $ 158.3 $ — $ 158.3 $ — $ — $ — Nebulized Tyvaso (1) 477.1 25.5 502.6 708.6 6.1 714.7 600.7 6.8 607.5 Total Tyvaso 1,208.2 25.5 1,233.7 866.9 6.1 873.0 600.7 6.8 607.5 Remodulin (2) 414.6 80.2 494.8 407.5 92.7 500.2 423.4 90.3 513.7 Orenitram 359.4 — 359.4 325.1 — 325.1 306.1 — 306.1 Unituxin 181.3 17.6 198.9 170.5 12.4 182.9 178.1 24.2 202.3 Adcirca 28.9 — 28.9 41.3 — 41.3 55.9 — 55.9 Other 9.8 2.0 11.8 2.8 11.0 13.8 — — — Total revenues $ 2,202.2 $ 125.3 $ 2,327.5 $ 1,814.1 $ 122.2 $ 1,936.3 $ 1,564.2 $ 121.3 $ 1,685.5 (1) Net product sales include both the drug product and the respective inhalation device.
ROW Total Net product sales: Tyvaso DPI (1) $ 1,033.2 $ 0.4 $ 1,033.6 $ 731.1 $ — $ 731.1 $ 158.3 $ — $ 158.3 Nebulized Tyvaso (1) 545.5 41.3 586.8 477.1 25.5 502.6 708.6 6.1 714.7 Total Tyvaso 1,578.7 41.7 1,620.4 1,208.2 25.5 1,233.7 866.9 6.1 873.0 Remodulin (2) 464.2 73.9 538.1 414.6 80.2 494.8 407.5 92.7 500.2 Orenitram 434.3 — 434.3 359.4 — 359.4 325.1 — 325.1 Unituxin 219.6 19.1 238.7 181.3 17.6 198.9 170.5 12.4 182.9 Adcirca 23.8 — 23.8 28.9 — 28.9 41.3 — 41.3 Other 19.1 3.0 22.1 9.8 2.0 11.8 2.8 11.0 13.8 Total revenues $ 2,739.7 $ 137.7 $ 2,877.4 $ 2,202.2 $ 125.3 $ 2,327.5 $ 1,814.1 $ 122.2 $ 1,936.3 (1) Net product sales include both the drug product and the respective inhalation device.
The 2022 Credit Agreement will mature in March 2028. As of December 31, 2023, we have classified $300.0 million of the outstanding balance as a non-current liability and $400.0 million as a current liability on our consolidated balance sheet, as we intend to repay this amount within one year.
The 2022 Credit Agreement will mature in March 2029. As of December 31, 2024, we have classified the outstanding balance of $300.0 million as a current liability on our consolidated balance sheet, as we intend to repay this amount within one year. See Note 7— Debt to our consolidated financial statements for further details.
Investing Activities The decrease of $91.9 million in net cash used in investing activities for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily due to a $306.3 million decrease in cash used for total purchases, sales, and maturities of marketable investments; partially offset by: (1) a $91.6 million increase in cash paid to purchase property, plant, and equipment; (2) $89.2 million in net cash paid related to the acquisitions of IVIVA and Miromatrix; and (3) $23.0 million in deposits.
Investing Activities The increase of $1,136.8 million in net cash provided by investing activities for the year ended December 31, 2024, as compared to the same period in 2023, was primarily due to: (1) a $1,099.7 million decrease in cash used for total purchases, sales, and maturities of marketable investments; and (2) an $89.2 million decrease in net cash paid related to the acquisitions of IVIVA and Miromatrix in 2023; partially offset by: (1) a $30.5 million increase in cash paid to purchase investments in privately-held companies; (2) a $16.1 million increase in cash paid to purchase property, plant, and equipment; and (3) a $5.5 million increase in deposits.
Health Resource Services Administration ( HRSA ) related to the Public Health Service’s 340B drug pricing program (the 340B program ); • The impact of competing therapies on sales of our commercial products, including the impact of generic versions of Remodulin; established therapies such as Uptravi; and newly-developed therapies such as Merck’s sotatercept and Liquidia’s Yutrepia; • The expectation that we will be able to manufacture sufficient quantities and maintain adequate inventories of our commercial products, through both our in-house manufacturing capabilities and third-party manufacturing sites (including our plans to expand manufacturing capacity for Tyvaso DPI), and our ability to obtain and maintain related approvals by the FDA and its international counterparts; • Expectations regarding the amount and timing of capital expenditures to construct new facilities to support our product development and commercialization efforts; • Expectations regarding the timing and impact of our business development efforts; • The adequacy of our intellectual property protection and the validity and expiration dates of the patents we own or license, as well as the regulatory exclusivity periods for our products; • The effect of our conversion to a Delaware public benefit corporation ( PBC ); • Any statements that include the words “believe,” “seek,” “expect,” “anticipate,” “forecast,” “project,” “intend,” “estimate,” “should,” “could,” “may,” “will,” “plan,” or similar expressions; and • Other statements contained or incorporated by reference in this Report that are not historical facts.
( Liquidia ) related to its new drug application ( NDA ) for Yutrepia; Liquidia’s lawsuit against the FDA related to the FDA’s decision to grant us a period of exclusivity and our cross-claims against the FDA related to Liquidia’s efforts to add an indication for PH-ILD to the NDA for Yutrepia; and our litigation with Humana Inc., United Healthcare Services, Inc., MSP Recovery Claims, Series LLC, and related entities; • The impact of competing therapies on sales of our commercial products, including the impact of generic versions of Remodulin; established therapies such as Uptravi; and therapies such as Merck’s recently-approved Winrevair and Liquidia’s Yutrepia, if it is approved by the FDA; • The expectation that we will be able to manufacture sufficient quantities and maintain adequate inventories of our commercial products, through both our in-house manufacturing capabilities and third-party manufacturing sites (including our plans to expand manufacturing capacity for Tyvaso DPI); • Expectations regarding the amount and timing of capital expenditures to construct new facilities to support our product development and commercialization efforts; • Expectations regarding the timing and impact of our business development efforts; • The adequacy of our intellectual property protection and the validity and expiration dates of the patents we own or license, as well as the regulatory exclusivity periods for our products; • Any statements that include the words “believe,” “seek,” “expect,” “anticipate,” “forecast,” “project,” “intend,” “estimate,” “should,” “could,” “may,” “will,” “plan,” or similar expressions; and • Other statements contained or incorporated by reference in this Report that are not historical facts.
We caution you that these statements are not guarantees of future performance and are subject to numerous evolving risks and uncertainties that we may not be able to accurately predict or assess, and that may cause our actual results to differ materially from anticipated results, including the risks and uncertainties we describe in Part I, Item 1A—Risk Factors of this Report and risks and uncertainties described in other cautionary statements, cautionary language, and risk factors set forth in our other filings with the SEC. 2023 Annual Report 53 Overview of Marketed Products We market and sell the following commercial products: • Tyvaso DPI and Nebulized Tyvaso.
We caution you that these statements are not guarantees of future performance and are subject to numerous evolving risks and uncertainties that we may not be able to accurately predict or assess, and that may cause our actual results to differ materially from anticipated results, including the risks and uncertainties we describe in Part I, Item 1A—Risk Factors of this Report and risks and uncertainties described in other cautionary statements, cautionary language, and risk factors set forth in our other filings with the SEC. 54 United Therapeutics, a public benefit corporation Overview of Marketed Products We market and sell the following commercial products: • Tyvaso DPI , a dry powder inhaled formulation of the prostacyclin analogue treprostinil, approved by the FDA in May 2022 to improve exercise ability in patients with pulmonary arterial hypertension ( PAH ) and PH-ILD.
(5) Other primarily includes upfront fees and milestone payments to third parties under license agreements related to development-stage products, adjustments to the fair value of our contingent consideration obligations, costs to acquire certain IPR&D assets, and a one-time expense associated with the redemption of a pediatric disease priority review voucher in 2021.
(4) Other primarily includes upfront fees and milestone payments to third parties under license agreements related to development-stage products, adjustments to the fair value of our contingent consideration obligations, and costs to acquire certain in-process research and development ( IPR&D ) assets.
Revenues The table below presents the components of total revenues (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2023 2022 2021 2023 v. 2022 2022 v. 2021 2023 v. 2022 2022 v. 2021 Net product sales: Tyvaso DPI (1) $ 731.1 $ 158.3 $ — $ 572.8 $ 158.3 362 % NM (3) Nebulized Tyvaso (1) 502.6 714.7 607.5 (212.1) 107.2 (30) % 18 % Total Tyvaso 1,233.7 873.0 607.5 360.7 265.5 41 % 44 % Remodulin (2) 494.8 500.2 513.7 (5.4) (13.5) (1) % (3) % Orenitram 359.4 325.1 306.1 34.3 19.0 11 % 6 % Unituxin 198.9 182.9 202.3 16.0 (19.4) 9 % (10) % Adcirca 28.9 41.3 55.9 (12.4) (14.6) (30) % (26) % Other 11.8 13.8 — (2.0) 13.8 (14) % NM (3) Total revenues $ 2,327.5 $ 1,936.3 $ 1,685.5 $ 391.2 $ 250.8 20 % 15 % 56 United Therapeutics, a public benefit corporation (1) Net product sales include both the drug product and the respective inhalation device.
Revenues The table below presents the components of total revenues (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2024 2023 2022 2024 v. 2023 2023 v. 2022 2024 v. 2023 2023 v. 2022 Net product sales: Tyvaso DPI (1) $ 1,033.6 $ 731.1 $ 158.3 $ 302.5 $ 572.8 41 % 362 % Nebulized Tyvaso (1) 586.8 502.6 714.7 84.2 (212.1) 17 % (30) % Total Tyvaso 1,620.4 1,233.7 873.0 386.7 360.7 31 % 41 % Remodulin (2) 538.1 494.8 500.2 43.3 (5.4) 9 % (1) % Orenitram 434.3 359.4 325.1 74.9 34.3 21 % 11 % Unituxin 238.7 198.9 182.9 39.8 16.0 20 % 9 % Adcirca 23.8 28.9 41.3 (5.1) (12.4) (18) % (30) % Other 22.1 11.8 13.8 10.3 (2.0) 87 % (14) % Total revenues $ 2,877.4 $ 2,327.5 $ 1,936.3 $ 549.9 $ 391.2 24 % 20 % (1) Net product sales include both the drug product and the respective inhalation device.
See Note 7— Debt, to our consolidated financial statements. 2023 Annual Report 61 Contractual Obligations As of December 31, 2023, we had the following contractual obligations (in millions): Payments Due by Period Total Less than 1 year 2-3 Years 4-5 Years More than 5 Years Operating lease obligations $ 32.8 $ 4.7 $ 8.5 $ 8.1 $ 11.5 Long-term debt obligations (1) 822.3 441.5 49.7 331.1 — Obligations under the STAP (2) 31.3 31.3 — — — Obligations under the SERP (3) 61.0 30.5 — 11.2 19.3 Purchase obligations (4) 772.2 586.6 150.8 26.1 8.7 Total (5) (6) $ 1,719.6 $ 1,094.6 $ 209.0 $ 376.5 $ 39.5 (1) Long-term debt obligations include future principal and interest payments on our adjusted variable rate obligations under the 2022 Credit Agreement.
See Note 7— Debt, to our consolidated financial statements. 2024 Annual Report 63 Contractual Obligations As of December 31, 2024, we had the following contractual obligations (in millions): Payments Due by Period Total Less than 1 year 2-3 Years 4-5 Years More than 5 Years Operating lease obligations $ 38.6 $ 6.1 $ 12.1 $ 10.8 $ 9.6 Long-term debt obligations (1) 341.3 314.6 16.4 10.3 — Obligations under the STAP (2) 10.5 10.5 — — — Obligations under the SERP (3) 63.2 30.8 — 12.2 20.2 Purchase obligations (4) 1,139.4 829.1 277.0 28.3 5.0 Total (5) (6) $ 1,593.0 $ 1,191.1 $ 305.5 $ 61.6 $ 34.8 (1) Long-term debt obligations include future principal and interest payments on our adjusted variable rate obligations under the 2022 Credit Agreement.
We are studying nebulized Tyvaso in patients with idiopathic pulmonary fibrosis and progressive pulmonary fibrosis (the TETON studies). In addition, we are developing a new product to treat PAH, ralinepag. We are also heavily engaged in research and development of a number of organ transplantation-related technologies including xenotransplantation, regenerative medicine, bio-artificial organs, 3-D organ bioprinting, and ex vivo lung perfusion.
In addition, we are developing a new product to treat PAH, ralinepag. We are also heavily engaged in research and development of organ transplantation-related technologies including xenotransplantation, regenerative medicine, bio-artificial organ alternatives, 3D organ alternative bioprinting, and ex vivo lung perfusion.
(2) Net product sales include sales of infusion devices including the Remunity Pump. (3) Calculation is not meaningful. Total Tyvaso net product sales grew 41% to $1,233.7 million in 2023, compared to $873.0 million for 2022.
(2) Net product sales include sales of infusion devices, including the Remunity Pump. Total Tyvaso net product sales grew 31 percent to $1,620.4 million in 2024, compared to $1,233.7 million for 2023.
The increase in cost of sales for the year ended December 31, 2023, as compared to the same period in 2022, was primarily due to an increase in Tyvaso DPI royalty expense and product costs, following its commercial launch in June 2022, and an increase in Remunity product sales. 58 United Therapeutics, a public benefit corporation Research and Development The table below summarizes the nature of research and development expense by major expense category (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2023 2022 2021 2023 v. 2022 2022 v. 2021 2023 v. 2022 2022 v. 2021 Category: External research and development (1) $ 192.0 $ 168.8 $ 156.7 $ 23.2 $ 12.1 14 % 8 % Internal research and development (2) 146.6 131.4 117.2 15.2 14.2 12 % 12 % Share-based compensation expense (3) 15.6 23.8 24.4 (8.2) (0.6) (34) % (2) % Impairments (4) — — 130.0 — (130.0) — % (100) % Other (5) 53.8 (1.1) 111.8 54.9 (112.9) NM (6) (101) % Total research and development expense $ 408.0 $ 322.9 $ 540.1 $ 85.1 $ (217.2) 26 % (40) % (1) External research and development primarily includes fees paid to third parties (such as clinical trial sites, contract research organizations, and contract laboratories) for preclinical and clinical studies and payments to third-party contract manufacturers before FDA approval of the relevant product.
Research and Development The table below summarizes the nature of research and development expense by major expense category (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2024 2023 2022 2024 v. 2023 2023 v. 2022 2024 v. 2023 2023 v. 2022 Category: External research and development (1) $ 217.5 $ 192.0 $ 168.8 $ 25.5 $ 23.2 13 % 14 % Internal research and development (2) 183.6 146.6 131.4 37.0 15.2 25 % 12 % Share-based compensation expense (3) 29.1 15.6 23.8 13.5 (8.2) 87 % (34) % Other (4) 50.8 53.8 (1.1) (3.0) 54.9 (6) % NM (5) Total research and development expense $ 481.0 $ 408.0 $ 322.9 $ 73.0 $ 85.1 18 % 26 % (1) External research and development primarily includes fees paid to third parties (such as clinical trial sites, contract research organizations, and contract laboratories) for preclinical and clinical studies and payments to third-party contract manufacturers before FDA approval of the relevant product.
As a result, sales of our treprostinil-based therapies can vary depending on the timing and magnitude of these orders and do not precisely reflect changes in patient demand.
Our specialty pharmaceutical distributors typically place monthly or semi-monthly orders based on current utilization trends and contractual minimum and maximum inventory requirements. As a result, sales of our treprostinil-based therapies can vary depending on the timing and magnitude of these orders and do not precisely reflect changes in patient demand.
Selling, General, and Administrative The table below summarizes selling, general, and administrative expense by major category (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2023 2022 2021 2023 v. 2022 2022 v. 2021 2023 v. 2022 2022 v. 2021 Category: General and administrative $ 374.2 $ 333.2 $ 294.3 $ 41.0 $ 38.9 12 % 13 % Sales and marketing 81.8 70.8 64.4 11.0 6.4 16 % 10 % Share-based compensation expense (1) 21.1 78.1 108.3 (57.0) (30.2) (73) % (28) % Total selling, general, and administrative expense $ 477.1 $ 482.1 $ 467.0 $ (5.0) $ 15.1 (1) % 3 % (1) See Share-Based Compensation section below for discussion.
Selling, General, and Administrative The table below summarizes selling, general, and administrative expense by major category (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2024 2023 2022 2024 v. 2023 2023 v. 2022 2024 v. 2023 2023 v. 2022 Category: General and administrative (1) $ 432.8 $ 374.2 $ 333.2 $ 58.6 $ 41.0 16 % 12 % Litigation accrual 71.1 — — 71.1 — NM (3) — % Sales and marketing 96.3 81.8 70.8 14.5 11.0 18 % 16 % Share-based compensation expense (2) 109.5 21.1 78.1 88.4 (57.0) 419 % (73) % Total selling, general, and administrative expense $ 709.7 $ 477.1 $ 482.1 $ 232.6 $ (5.0) 49 % (1) % (1) Excluding litigation accrual.
Remodulin net product sales decreased in 2023, as compared to 2022, due to a decrease in international net product sales, partially offset by an increase in U.S. Remodulin net product sales, as shown in the table below. Orenitram net product sales increased in 2023, as compared to 2022, due to a price increase and an increase in quantities sold.
Remodulin net product sales increased in 2024, as compared to 2023, primarily due to an increase in U.S. Remodulin net product sales, driven by an increase in quantities sold. Orenitram net product sales increased in 2024, as compared to 2023, primarily due to an increase in quantities sold and, to a lesser extent, a price increase.
These pharmaceutical companies are well established in the market and possess greater financial, technical, and marketing resources than we do.
We operate in a highly competitive market in which several large pharmaceutical companies control many of the available PAH therapies. These pharmaceutical companies are well established in the market and possess greater financial, technical, and marketing resources than we do.
The increase in general and administrative expense for the year ended December 31, 2023, as compared to the same period in 2022, was primarily due to increases in: (1) office expenses; (2) personnel expense due to growth in headcount; and (3) sponsorships and grants. 2023 Annual Report 59 Sales and marketing, excluding share-based compensation .
The increase in general and administrative expense for the year ended December 31, 2024, as compared to the same period in 2023, was primarily due to increases in: (1) personnel expense due to growth in headcount; (2) legal expenses related to litigation matters; and (3) consulting expenses. Litigation accrual.
In June 2023, our contract manufacturer obtained FDA clearance for a cartridge to be used with the CADD-MS3 ambulatory infusion pump for subcutaneous infusion of Remodulin. • Orenitram , an extended-release tablet dosage form of treprostinil, approved by the FDA to delay disease progression and improve exercise capacity in PAH patients. • Unituxin , a monoclonal antibody approved in the United States, Canada, and Japan for the treatment of high-risk neuroblastoma. • Adcirca , an oral PDE-5 inhibitor approved by the FDA to improve exercise ability in PAH patients.
In February 2021, we launched U.S. sales of the Remunity Pump, a next-generation subcutaneous infusion system for Remodulin. • Orenitram , an oral extended-release tablet form of treprostinil, approved by the FDA to delay disease progression and improve exercise capacity in PAH patients. • Unituxin , an infused monoclonal antibody approved in the United States and Canada for the treatment of high-risk neuroblastoma and approved in Japan for the treatment of neuroblastoma after high-dose chemotherapy. • Adcirca , an oral immediate-release tablet form of the PDE-5 inhibitor tadalafil, approved by the FDA to improve exercise ability in PAH patients.
The increase in research and development expense for the year ended December 31, 2023, as compared to the same period in 2022, was due to: (1) an increase in IPR&D expense in connection with the acquisition of IVIVA; (2) increased expenditures related to the TETON 1 and TETON 2 clinical studies of nebulized Tyvaso in patients with IPF; and (3) increased expenditures related to organ manufacturing projects.
The increase in research and development expense for the year ended December 31, 2024, as compared to the same period in 2023, was due to: (1) increased expenditures related to manufactured organ and organ alternative projects; (2) non-refundable licensing payments for drug delivery device technologies and ex vivo lung perfusion technology; and (3) increased expenditures related to the TETON studies of nebulized Tyvaso in patients with IPF and PPF.
Financing Activities The increase of $87.3 million in net cash used in financing activities for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily due to a $100.0 million repayment on our line of credit; partially offset by: (1) a $9.6 million increase in proceeds from the exercise of stock options; and (2) a $4.8 million decrease in payments of debt issuance costs related to the 2022 Credit Agreement.
Financing Activities The increase of $1,242.9 million in net cash used in financing activities for the year ended December 31, 2024, as compared to the same period in 2023, was primarily due to: (1) a $1.0 billion payment in 2024 to repurchase shares of our common stock; and (2) a $300.0 million increase in cash paid for repayments on our line of credit; partially offset by a $54.5 million increase in proceeds from the exercise of stock options.
Nebulized Tyvaso was also approved in Argentina to treat PH-ILD in February 2023. • Remodulin , a continuously-infused formulation of treprostinil, approved by the FDA for subcutaneous and intravenous administration to diminish symptoms associated with exercise in PAH patients. Remodulin has also been approved in various countries outside of the United States.
In addition, marketing authorization applications for nebulized Tyvaso to treat PAH and/or PH-ILD have also been approved, and others are pending, in various other countries in Latin America, Asia, and the Middle East. • Remodulin , a continuously-infused formulation of treprostinil, approved by the FDA for subcutaneous and intravenous delivery to diminish symptoms associated with exercise in patients with PAH.
Nebulized Tyvaso is an inhaled formulation of the prostacyclin analogue treprostinil, approved by the FDA and regulatory authorities in Argentina, Israel, and Japan to improve exercise ability in patients with pulmonary arterial hypertension ( PAH ).
We initiated commercial shipments of Tyvaso DPI to our U.S. distributors in June 2022. • Nebulized Tyvaso, a liquid inhaled formulation of treprostinil, approved by the FDA and regulatory authorities in Argentina, Israel, and Japan to improve exercise ability in patients with PAH.
This growth was primarily due to an increase in quantities sold, driven by the commercial launch of Tyvaso DPI in June 2022 and continued growth in utilization by PH-ILD patients. Tyvaso DPI net product sales increased in 2023, as compared to 2022, primarily due to an increase in quantities sold.
Nebulized Tyvaso net product sales increased in 2024, as compared to 2023, primarily due to higher quantities sold of $51.9 million and, to a lesser extent, a price increase. Growth in nebulized Tyvaso was also driven by continued growth in use by PH-ILD patients.
For information regarding the fluctuation explanations between 2022 and 2021 , see our 2022 Annual Report. 60 United Therapeutics, a public benefit corporation Cash and Cash Equivalents and Marketable Investments Cash and cash equivalents and marketable investments comprise the following (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2023 2022 2023 v. 2022 2023 v. 2022 Cash and cash equivalents $ 1,207.7 $ 961.2 $ 246.5 26 % Marketable investments—current 1,786.4 1,877.5 (91.1) (5) % Marketable investments—non-current 1,909.8 1,316.2 593.6 45 % Total cash and cash equivalents and marketable investments $ 4,903.9 $ 4,154.9 $ 749.0 18 % Cash Flows Cash flows comprise the following (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2023 2022 2021 2023 v. 2022 2022 v. 2021 2023 v. 2022 2022 v. 2021 Net cash provided by operating activities $ 978.0 $ 802.5 $ 598.2 $ 175.5 $ 204.3 22 % 34 % Net cash used in investing activities $ (719.6) $ (811.5) $ (486.9) $ 91.9 $ (324.6) 11 % (67) % Net cash (used in) provided by financing activities $ (11.9) $ 75.4 $ 44.8 $ (87.3) $ 30.6 (116) % 68 % Operating Activities Our operating assets and liabilities consist primarily of accounts receivable, inventories, accounts payable, accrued expenses, liabilities for our STAP awards, and tax-related payables and receivables.
For information regarding the fluctuation explanations between 2023 and 2022 , see our 2023 Annual Report. 62 United Therapeutics, a public benefit corporation Cash and Cash Equivalents and Marketable Investments Cash and cash equivalents and marketable investments comprise the following (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2024 2023 2024 v. 2023 2024 v. 2023 Cash and cash equivalents $ 1,697.2 $ 1,207.7 $ 489.5 41 % Marketable investments—current 1,569.8 1,786.4 (216.6) (12) % Marketable investments—non-current 1,475.3 1,909.8 (434.5) (23) % Total cash and cash equivalents and marketable investments $ 4,742.3 $ 4,903.9 $ (161.6) (3) % Cash Flows Cash flows comprise the following (dollars in millions): Year Ended December 31, Dollar Change Percentage Change 2024 2023 2022 2024 v. 2023 2023 v. 2022 2024 v. 2023 2023 v. 2022 Net cash provided by operating activities $ 1,327.1 $ 978.0 $ 802.5 $ 349.1 $ 175.5 36 % 22 % Net cash provided by (used in) investing activities $ 417.2 $ (719.6) $ (811.5) $ 1,136.8 $ 91.9 158 % 11 % Net cash (used in) provided by financing activities $ (1,254.8) $ (11.9) $ 75.4 $ (1,242.9) $ (87.3) NM (1) (116) % (1) Calculation is not meaningful.
We believe that our current sources of liquidity are sufficient to fund ongoing operations and future business plans as we expect aggregate growth in revenues from our commercial products. Furthermore, our customer base remains stable and we believe that it presents minimal credit risk.
Financial Condition, Liquidity, and Capital Resources We have funded our operations principally through sales of our commercial products and, from time-to-time, third-party financing arrangements. We believe that our current sources of liquidity are sufficient to fund ongoing operations and future business plans as we expect aggregate growth in revenues from our commercial products.
Our aggregate outstanding balance under the 2022 Credit Agreement was $700.0 million and $800.0 million as of December 31, 2023 and 2022, respectively .
In March 2022, we entered into a credit agreement (the 2022 Credit Agreement ), which provides for unsecured revolving credit facilities of up to $2.0 billion in the aggregate. Our aggregate outstanding balance under the 2022 Credit Agreement was $300.0 million and $700.0 million as of December 31, 2024 and 2023, respectively .
For additional information on the assumptions used in the Black-Scholes-Merton valuation model, see Note 8— Share-Based Compensation, to our consolidated financial statements. Recently Issued Accounting Standards See Note 3— Recently Issued Accounting Standards , to our consolidated financial statements for information on our anticipated adoption of recently issued accounting standards. 2023 Annual Report 63
Recently Issued Accounting Standards See Note 3— Recently Issued Accounting Standards , to our consolidated financial statements for information on our adoption and anticipated adoption of recently issued accounting standards.
The increase of $175.5 million in net cash provided by operating activities for the year ended December 31, 2023, as compared to the year ended December 31, 2022, was primarily due to: (1) a $53.5 million decrease in cash paid to settle STAP awards; and (2) changes in other assets and liabilities.
The increase of $349.1 million in net cash provided by operating activities for the year ended December 31, 2024, as compared to the same period in 2023, was primarily due to an increase in net cash received due to the growth in sales of our commercial products.
Share-Based Compensation Historically, we granted stock options under our Amended and Restated Equity Incentive Plan and awards under our Share Tracking Awards Plan (the STAP ). Issuance of awards under both of these plans was discontinued in 2015.
Issuance of awards under both of these plans was discontinued in 2015, and as of December 31, 2024, there were no longer any awards outstanding under our Amended and Restated Equity Incentive Plan.
We have budgeted for capital expenditures of approximately $500 million during 2024-2026 in order to construct additional facilities to support the development and commercialization of our products and technologies. We plan to dedicate the majority of this budget to constructing a new Tyvaso DPI manufacturing facility in Research Triangle Park, North Carolina.
We have budgeted approximately $750 million for capital expenditures during 2025 through the end of 2027 to construct additional facilities to support the development and commercialization of our products and technologies.
General and administrative expenses also include our core corporate support functions such as human resources, finance, and legal, and external costs to support our core business such as insurance premiums, legal fees, and other professional service fees.
General and administrative expenses include the core corporate support functions such as human resources, finance, and legal, and associated external costs to support those functions. Share-Based Compensation Historically, we granted stock options under our Amended and Restated Equity Incentive Plan and awards under our Share Tracking Awards Plan (the STAP ).
However, any projections of future cash flows are inherently subject to uncertainty and we may seek other forms of financing. In March 2022, we entered into a credit agreement (the 2022 Credit Agreement ), which provides for unsecured revolving credit facilities of up to $2.0 billion in the aggregate.
Furthermore, our customer base remains stable, and we believe that it presents minimal credit risk. However, any projections of future cash flows are inherently subject to uncertainty and we may seek other forms of financing.
Nebulized Tyvaso net product sales decreased in 2023, as compared to 2022, driven by a decrease in U.S. nebulized Tyvaso net product sales, primarily due to a decrease in quantities sold following the commercial launch of Tyvaso DPI, partially offset by an increase in international nebulized Tyvaso net product sales, primarily due to the commercial launch of nebulized Tyvaso in Japan in December 2022, as shown in the table below.
Tyvaso DPI net product sales increased in 2024, as compared to 2023, due to an increase in quantities sold of $269.2 million and, to a lesser extent, price increases, partially offset by higher gross-to-net revenue deductions.
In 2021, we launched a new pump for subcutaneous delivery of Remodulin, called the Remunity Pump, and are currently developing a new version of the Remunity Pump. We are also working with a medical device manufacturer to develop new delivery systems for Remodulin.
In 2021, we launched a new pump for subcutaneous delivery of Remodulin, called the Remunity Pump, and recently completed development of a new version of the Remunity Pump, called RemunityPRO, which was cleared by the FDA in January 2025. We are studying nebulized Tyvaso in patients with idiopathic pulmonary fibrosis and progressive pulmonary fibrosis (the TETON studies).
We require our specialty pharmaceutical distributors to maintain reasonable levels of inventory reserves for our treprostinil-based therapies because the interruption of these therapies can be life threatening. Our specialty pharmaceutical distributors typically place monthly or semi-monthly orders based on current utilization trends and contractual minimum and maximum inventory requirements.
We also derive revenues from the sale of commercial ex vivo lung perfusion services, which are presented under Other within Note 13— Segment Information to our consolidated financial statements included in this Report. We require our specialty pharmaceutical distributors to maintain reasonable levels of inventory reserves for our treprostinil-based therapies because the interruption of these therapies can be life threatening.
Removed
( Liquidia ) related to its new drug application ( NDA ) for Yutrepia; our lawsuit against the FDA related to Liquidia’s efforts to add PH-ILD to the NDA for Yutrepia; our litigation with Humana Inc., United Healthcare Services, Inc., MSP Recovery Claims, Series LLC, and related entities; and our litigation with the U.S.
Added
Remodulin has also been approved in various countries outside of the United States.
Removed
Department of Health and Human Services ( HHS ) and the U.S.
Added
This amount is primarily dedicated to construction of a new Tyvaso DPI manufacturing facility in Research Triangle Park, North Carolina ( RTP ); construction of a clinical-scale designated pathogen-free ( DPF ) facility in Stewartville, Minnesota; and initial pre-construction activities for a commercial-scale DPF facility. We plan to fund these capital expenditures using cash on hand.
Removed
In May 2022, we also obtained FDA approval of a dry powder formulation of treprostinil for inhalation known as Tyvaso DPI to treat PAH and PH-ILD, and we initiated commercial shipments of Tyvaso DPI to our distributors in June 2022.
Added
We anticipate our first commercial-scale DPF facility will provide an initial commercial supply of our xeno-organ products if and when they are approved by the FDA.
Removed
Nebulized Tyvaso was also approved to treat PAH in Japan in late 2022, and our Japanese distributor launched commercial sales in Japan during the second quarter of 2023, and submitted an application in December 2023 to add a PH-ILD indication.
Added
Our commercial-scale DPF facilities will be very capital-intensive, but they will be executed in stages with the ability to adjust the schedule (and anticipated cost) depending on the progress of our clinical and regulatory activities.
Removed
In February 2021, we launched U.S. sales of the Remunity Pump, a new subcutaneous infusion system for Remodulin.
Added
In addition to the production capacity of our commercial-scale DPF facility, we anticipate additional commercial capacity stemming from at least three clinical-scale facilities: our existing DPF facility in Virginia; a DPF facility we are building in Minnesota, as noted above; and a third clinical-scale DPF facility we plan to build in Houston, Texas.
Removed
We plan to fund these capital expenditures using cash on hand. If and when we commence construction of commercial-scale designated pathogen-free facilities to produce porcine organs for xenotransplantation, the rate of our capital expenditures will increase substantially. We operate in a highly competitive market in which a small number of large pharmaceutical companies control a majority of available PAH therapies.
Added
For example, Yutrepia has been tentatively approved by the FDA for the treatment of PAH and PH-ILD, with final approval potentially occurring after expiration of an exclusivity period ending in May 2025.
Removed
(4) Impairments primarily includes impairment charges to write down the carrying value of in-process research and development ( IPR&D ) and of certain property, plant, and equipment as a result of research and development activities. During the years ended December 31, 2023, 2022, and 2021, we recorded impairment charges of zero, zero, and $130.0 million, respectively.
Added
The increase in Tyvaso DPI quantities sold was primarily due to continued growth in the number of patients following the product’s launch (including by PH-ILD patients) and, to a lesser extent, increased commercial utilization following implementation of the Part D redesign under the Inflation Reduction Act.
Removed
Our effective income tax rate was approximately 23 percent for the years ended December 31, 2023 and 2022. For additional details, see Note 10— Income Taxes to our consolidated financial statements. Financial Condition, Liquidity, and Capital Resources We have funded our operations principally through sales of our commercial products and, from time-to-time, third-party financing arrangements.
Added
The increase in quantities sold was driven, at least in part, by increased commercial utilization following the implementation of the Part D redesign under the Inflation Reduction Act.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

6 edited+0 added−0 removed2 unchanged
Biggest changeThe following table summarizes the expected maturities and weighted average interest rates as of December 31, 2023 (dollars in millions): Expected Maturity 2024 2025 2026 Available-for-sale investments $ 1,886.2 $ 1,477.7 $ 393.2 Weighted average interest rate 1.7 % 3.1 % 4.2 % During sustained periods of instability and uncertainty in the financial markets, we may be subjected to additional investment-related risks that could materially affect the value and liquidity of our investments.
Biggest changeMany of our investments may be called by their respective issuers prior to maturity. 2024 Annual Report 65 The following table summarizes the expected maturities and weighted average interest rates as of December 31, 2024 (dollars in millions): Expected Maturity 2025 2026 2027 Available-for-sale investments $ 1,567.4 $ 1,071.7 $ 403.6 Weighted average interest rate 3.3 % 4.1 % 4.1 % During sustained periods of instability and uncertainty in the financial markets, we may be subjected to additional investment-related risks that could materially affect the value and liquidity of our investments.
Interest Rate Risk As of December 31, 2023 and 2022, we had $700.0 million and $800.0 million aggregate principal amounts, respectively, outstanding under our 2022 Credit Agreement which bears interest at a variable rate. As a result, we are subject to interest rate risk with respect to such floating-rate debt.
Interest Rate Risk As of December 31, 2024 and 2023, we had $300.0 million and $700.0 million aggregate principal amounts, respectively, outstanding under our 2022 Credit Agreement which bears interest at a variable rate. As a result, we are subject to interest rate risk with respect to such floating-rate debt.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk Investment Risk As of December 31, 2023, we have invested $3.8 billion in corporate debt securities and U.S. government and agency securities. The market value of these investments varies inversely with changes in prevailing market interest rates.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk Investment Risk As of December 31, 2024, we have invested $3.0 billion in corporate debt securities and U.S. government and agency securities. The market value of these investments varies inversely with changes in prevailing market interest rates.
A 100-basis point increase in the variable interest rate component of our borrowings would increase our annual interest expense by approximately $7.0 million or 12 percent, and $8.0 million or 25 percent, for the years ended December 31, 2023 and 2022, respectively. See Note 7— Debt, to our consolidated financial statements. 64 United Therapeutics, a public benefit corporation
A 100-basis point increase in the variable interest rate component of our borrowings would increase our annual interest expense by approximately $1.3 million or three percent, and $7.0 million or 12 percent, for the years ended December 31, 2024 and 2023, respectively. See Note 7— Debt, to our consolidated financial statements. 66 United Therapeutics, a public benefit corporation
To address market risk, we invest in debt securities with terms no longer than three years and typically hold these investments to maturity so that they can be redeemed at their stated or face value. Many of our investments may be called by their respective issuers prior to maturity.
To address market risk, we invest in debt securities with terms no longer than three years and typically hold these investments to maturity so that they can be redeemed at their stated or face value.
In general, as interest rates increase, the market value of a debt investment would be expected to decrease. Conversely, as interest rates decrease, the market value of a debt investment would be expected to increase. During 2023, we experienced significant volatility in the value of these investments as a direct result of the current interest rate environment.
In general, as interest rates increase, the market value of a debt investment would be expected to decrease. Conversely, as interest rates decrease, the market value of a debt investment would be expected to increase. During the year ended December 31, 2024, we did not experience significant volatility in the value of these investments.

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