UNITED THERAPEUTICS Corp (UTHR) Business

Item 1. Business

Overview

Founded by our Chairperson and Chief Executive Officer, Martine Rothblatt, to find a cure for her daughter’s life-threatening rare disease, pulmonary arterial hypertension (PAH), United Therapeutics advances therapies for people living with serious diseases with unmet medical needs. Our mission is to transform the treatment of rare diseases and expand the availability of transplantable organs through innovative organ manufacturing technologies.

As a public benefit corporation (PBC), we aim to deliver meaningful impacts for our patients, our people, our shareholders, and other stakeholders. Our public benefit purpose, as outlined in our charter and approved by our shareholders, is to provide a brighter future for patients through (a) the development of novel pharmaceutical therapies; and (b) technologies that expand the availability of transplantable organs.

We market and sell the following commercial therapies in the United States to treat PAH:

•Tyvaso DPI® (treprostinil) Inhalation Powder (Tyvaso DPI);

•Tyvaso® (treprostinil) Inhalation Solution (Nebulized Tyvaso), which includes the Tyvaso Inhalation System;

•Remodulin® (treprostinil) Injection (Remodulin); and the Remunity® and RemunityPRO™ Pumps for Remodulin (Remunity);

•Orenitram® (treprostinil) Extended-Release Tablets (Orenitram); and

•Adcirca® (tadalafil) Tablets (Adcirca).

Tyvaso DPI and Nebulized Tyvaso are also approved by the U.S. Food and Drug Administration (FDA) to treat pulmonary hypertension associated with interstitial lung disease (PH-ILD).

In the United States, we also market and sell an oncology product, Unituxin® (dinutuximab) Injection (Unituxin), which is approved by the FDA for the treatment of high-risk neuroblastoma. Outside the United States, we derive revenues from sales of Nebulized Tyvaso, Remodulin, and Unituxin.

We also have products in development for PAH, idiopathic pulmonary fibrosis (IPF), and progressive pulmonary fibrosis (PPF), and other diseases with unmet medical needs.

Our principal executive offices are located at 1000 Spring Street, Silver Spring, Maryland 20910 and at 55 T.W. Alexander Drive, Durham, North Carolina 27713. Unless the context requires otherwise or unless otherwise noted, all references in this Annual Report on Form 10-K (this Report) to “United Therapeutics” and to the “company”, “we”, “us” or “our” are to United Therapeutics Corporation and its subsidiaries.

Our Commercial Products

Our commercial product portfolio consists of the following:

*    Remodulin is marketed and sold in most of the major European markets other than the United Kingdom for both intravenous and subcutaneous administration. In the United Kingdom, Remodulin is sold on a named-patient basis only.

Products to Treat Pulmonary Hypertension

Pulmonary hypertension (PH) has been classified into five groups. PAH is designated as group 1 PH, which includes multiple etiologies such as idiopathic (meaning the cause is unknown) and heritable PAH, as well as PAH associated with connective tissue diseases. PH associated with lung disease, such as PH-ILD and pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD), has been classified as group 3 PH. In addition, patients with PAH are classified based on clinical severity, ranging from functional class I (no symptoms) through functional class IV (severe symptoms). Labeled indications for PAH therapies often note that clinical studies for the drug predominantly included patients in one or more functional classes.

Most of our PH products were initially approved to treat only PAH. 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. For further details, see Research and Development below.

PAH is a life-threatening disease that affects the blood vessels in the lungs and is characterized by increased pressure in the pulmonary arteries, which are the blood vessels leading from the heart to the lungs. The elevated pressure in the pulmonary arteries strains the right side of the heart as it pumps blood to the lungs. This eventually leads to right heart failure and, ultimately, death. PAH is characterized by structural changes in blood vessel walls, aggregation of platelets, and alteration of smooth muscle cell function. We believe that PAH affects about 500,000 individuals worldwide. We have seen increases in the number of people diagnosed with the disease, but due to the rarity of the disease and the complexity of diagnosing it, only a small fraction of patients with PAH are being treated.

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. Patients with PAH have been shown to have reduced levels of prostacyclin, a naturally occurring molecule that relaxes the pulmonary blood vessels, prevents platelet aggregation, and inhibits the proliferation of smooth muscle cells in the pulmonary vessels. Drugs that mimic the action of prostacyclin, known as prostacyclin analogues, are established PAH treatments. Another class of therapy, called IP prostacyclin receptor agonists, also addresses PAH through the prostacyclin pathway. As compared with prostacyclin analogues, which broadly mimic the effect of prostacyclin, IP prostacyclin receptor agonists bind selectively to (and activate) the IP receptor, one of several prostacyclin receptors.

•Phosphodiesterase Type 5 (PDE-5) Inhibitors and Soluble Guanylate Cyclase (sGC) Stimulators. Patients with PAH have also been shown to have reduced levels of the enzyme responsible for producing nitric oxide, a naturally occurring

substance in the body that causes relaxation of the pulmonary blood vessels. Nitric oxide produces this effect by increasing intracellular levels of cyclic guanosine monophosphate GMP (cyclic GMP). Therefore, another established therapeutic approach has been to inhibit the degradation of cyclic GMP using drugs known as PDE-5 inhibitors. In addition, sGC is an enzyme found in the endothelial cells and the receptor for nitric oxide. When nitric oxide binds to sGC, the enzyme enhances production of cyclic GMP. As a result, sGC stimulators are also approved to treat PAH.

•Endothelin Receptor Antagonists. PAH patients have also been shown to have elevated levels of endothelin-1, a naturally occurring peptide in the body that causes constriction of, and structural changes to, the pulmonary blood vessels. Therefore, another established therapeutic approach has been to block the action of endothelin with drugs that are known as endothelin receptor antagonists (ERAs).

•Activin Signaling Inhibitors. Activin signaling inhibitors aim to improve the balance between pro- and anti-proliferative signaling to regulate vascular cell proliferation underlying PAH. In March 2024, Merck & Co., Inc. (Merck) obtained FDA approval for the first activin signaling inhibitor, known as Winrevair® (sotatercept), to treat PAH, and launched sales of the product shortly thereafter.

Because any or all of these pathways may be therapeutic targets in a patient, these classes of drugs are used alone or in combination to treat patients with PAH. We currently market drugs in two of these classes. Tyvaso DPI, Nebulized Tyvaso, Remodulin, and Orenitram are all formulations of treprostinil, a prostacyclin analogue, and Adcirca is a PDE-5 inhibitor.

PH-ILD is also a rare condition, impacting at least 30,000 patients in the United States.

Tyvaso DPI and Nebulized Tyvaso

Tyvaso was initially approved as a nebulized product by the FDA to treat PAH and was launched commercially in the United States in 2009. 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. In May 2022, the FDA approved our dry powder formulation of inhaled treprostinil called Tyvaso DPI, for the treatment of both PAH and PH-ILD. We developed this product under an in-license from MannKind Corporation (MannKind) and launched this product commercially in the United States in June 2022.

We sell Tyvaso DPI and Nebulized Tyvaso to specialty pharmaceutical distributors in the United States. We recognized $1,878.2 million, $1,620.4 million, and $1,233.7 million in combined Tyvaso DPI and Nebulized Tyvaso net product sales, representing 59 percent, 56 percent, and 53 percent of our total revenues for the years ended December 31, 2025, 2024, and 2023, respectively. Nebulized Tyvaso is approved for PAH and PH-ILD in the United States and Japan, and it is also approved for PAH and/or PH-ILD in various countries in Asia, the Middle East, and Latin America. Tyvaso DPI is currently approved only in the United States.

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. 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.

Nebulized Tyvaso is administered four times a day using our proprietary Tyvaso Inhalation System, which consists of an ultrasonic nebulizer and related accessories. Dose titration is achieved by varying the number of breaths per treatment session typically starting at three breaths per session, and increasing the dose in three-breath increments during the titration process. A single ampule containing Nebulized Tyvaso solution is emptied into the Tyvaso Inhalation System once per day, so the Tyvaso Inhalation System only needs to be cleaned once daily. Nebulized Tyvaso is regulated by the FDA as a drug-device combination product approved under an NDA consisting of Tyvaso drug product and the Tyvaso Inhalation System.

Studies establishing the effectiveness of Nebulized Tyvaso to treat PAH included predominately PAH patients with functional class III symptoms (patients who may not have symptoms at rest but whose activities are greatly limited by shortness of breath, fatigue, or near fainting). Nebulized Tyvaso was generally well tolerated in these trials. The most common side effects were transient cough, headache, nausea, dizziness, and flushing. In January and June 2021, data from the INCREASE study of Nebulized Tyvaso for PH-ILD were published in the New England Journal of Medicine and The Lancet Respiratory Medicine, respectively.

Both Nebulized Tyvaso and Tyvaso DPI have no stated maximum dose; they may be titrated to an effective dose based on individual patient tolerability under the supervision of a health care provider.

Remodulin

Remodulin was approved by the FDA for subcutaneous and intravenous administration in 2002 and 2004, respectively, and has been sold commercially in the United States since 2002. We sell Remodulin to specialty pharmaceutical distributors in the United States and to pharmaceutical distributors internationally. We recognized $526.8 million, $538.1 million, and $494.8 million in Remodulin net product sales, representing 17 percent, 19 percent, and 21 percent of our total revenues for the years ended December 31, 2025, 2024, and 2023, respectively. Remodulin is indicated to treat patients with PAH to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with functional class II-IV (moderate to severe) symptoms. Outside of the United States, Remodulin is approved and commercialized for the treatment of PAH in most of Europe, Canada, Japan, and various other countries in Asia, the Middle East, and Latin America.

We believe that Remodulin has many qualities that make it an appealing alternative to competitive continuously infused PAH therapies. 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. 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. This profile contrasts favorably with non-treprostinil based, continuously infused prostacyclin therapies on the market: Veletri® and generic epoprostenol.

Generic epoprostenol is not stable at room temperature (and therefore requires refrigeration or the use of cooling packs), but Veletri may be stable at room temperature depending on its concentration. Generic epoprostenol and Veletri have shorter half-lives than Remodulin, requiring mixing prior to pump refills. Neither of these competitive products may be administered via subcutaneous infusion, and therefore may only be delivered intravenously which, unlike subcutaneous infusion, requires intravenous infusion line placement and carries the risk of serious bloodstream infection.

We also face competition from manufacturers of generic versions of Remodulin in the United States and abroad. See the section below entitled Patents and Other Proprietary Rights, Strategic Licenses, and Market Exclusivity—Generic Competition and Challenges to our Intellectual Property Rights.

Patients must use external pumps manufactured by third parties to deliver Remodulin. Historically, Smiths Medical, Inc. (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. In 2015, Smiths Medical notified us that it was planning to discontinue the manufacture of the MS-3 pumps and associated cartridges. In response, we funded Smiths Medical’s manufacture of several thousand additional MS-3 pumps and, in parallel, pursued development of the Remunity Pump so that PAH patients would not experience a delay or disruption in their Remodulin therapy. Our specialty pharmacy distributors informed us that supplies of new MS-3 pumps are fully exhausted, although a limited number of refurbished pumps may be available for use with generic treprostinil. In June 2023, our third-party contract manufacturer, Gilero LLC, which was later acquired by Sanner GmbH, obtained FDA clearance for a cartridge to be used with the MS-3 pump for subcutaneous infusion of Remodulin. As discussed below under Remunity and RemunityPRO Pumps, our Remunity and RemunityPRO Pumps are now the primary infusion systems used to deliver Remodulin subcutaneously. ICU Medical has also discontinued the CADD-Legacy system, and has made an alternative pump, the CADD-Solis™, available for intravenous infusion of Remodulin.

There are side effects associated with Remodulin. For example, when infused subcutaneously, Remodulin causes varying degrees of infusion site pain and reaction (redness and swelling) in most patients. Patients who cannot tolerate the infusion site pain related to the use of subcutaneous Remodulin may instead use intravenous Remodulin. Intravenous Remodulin is delivered continuously through a surgically implanted central venous catheter, similar to Veletri and generic epoprostenol. Patients who receive therapy through implanted venous catheters have a risk of developing bloodstream infections and a serious systemic infection known as sepsis. Other common side effects associated with both subcutaneous and intravenous Remodulin include headache, diarrhea, nausea, jaw pain, vasodilation, and edema.

Remodulin may require dilution prior to administration based on factors such as patient weight, desired dose, and desired infusion rate. Dilution may be performed with multiple approved sterile diluent solutions, as specified in the full prescribing information. To provide patients with a reliable supply of diluent solution, we manufacture and distribute Sterile Diluent for Remodulin, a high-pH glycine diluent.

Remunity and RemunityPRO Pumps

In February 2021, we launched commercial sales of the Remunity Pump, which is a semi-disposable system for subcutaneous delivery of treprostinil that we developed in collaboration with DEKA Research & Development Corp. (DEKA) under an exclusive development and license agreement. The Remunity Pump consists of a small, lightweight, durable pump and controller designed to have a service life of at least three years. The Remunity Pump uses disposable cassettes filled with Remodulin, which can be connected to the pump with less patient manipulation than is typically involved in filling other currently available subcutaneous pumps. In November 2019, we entered into a supply agreement with an affiliate of DEKA to manufacture and supply the Remunity Pump to us. Under the terms of the agreement, we reimburse all of DEKA’s and its affiliates’ costs to manufacture the Remunity Pump.

In January 2025, DEKA obtained FDA clearance of a new version of the Remunity Pump, which is intended to improve the patient experience by making the pump easier to use and will be offered only as a patient-filled device. We launched this new system, called RemunityPRO, in September 2025.

The majority of patients being treated with subcutaneous Remodulin in the United States are now using the Remunity or RemunityPRO Pump, and we believe that it is the only subcutaneous infusion system widely available in the United States for newly prescribed treprostinil patients, although a limited number of refurbished MS-3 pumps may be available for use with generic treprostinil. The Remunity and RemunityPRO Pumps are classified by the U.S. Centers for Medicare & Medicaid Services (CMS) as durable medical equipment. Net product sales of Remodulin include sales of the Remunity and RemunityPRO Pumps.

Orenitram

Orenitram is the only FDA-approved, orally-administered prostacyclin analogue, and is the only oral PAH prostacyclin class therapy approved in the United States that is titratable to a maximum tolerated dose without a dose ceiling. We sell Orenitram to the same specialty pharmaceutical distributors in the United States that distribute Tyvaso DPI, Nebulized Tyvaso, and Remodulin. We recognized $496.9 million, $434.3 million, and $359.4 million in Orenitram net product sales, representing 16 percent, 15 percent, and 15 percent of our total revenues for the years ended December 31, 2025, 2024, and 2023, respectively. In 2013, the FDA approved Orenitram for the treatment of PAH patients to improve exercise capacity. The primary study that supported efficacy of Orenitram was a 12-week monotherapy study in which PAH patients were not on any approved background PAH therapy. In August 2018, we announced that our clinical study of Orenitram called FREEDOM-EV had met its primary endpoint of delayed time to first clinical worsening event. 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). In October 2019, the FDA approved a supplement to the Orenitram NDA to update the product’s label to reflect the FREEDOM-EV results. As a result, Orenitram is indicated to delay disease progression and improve exercise capacity.

Secondary endpoints in the FREEDOM-EV study included changes from baseline in six-minute walk distance (6MWD), Borg dyspnea score (shortness of breath test), functional class, NT-proBNP levels, and combined 6MWD and Borg dyspnea score. Secondary endpoint data, which are not included in the updated FDA-approved labeling, are summarized below:

•Change in 6MWD: The median 6MWD trended toward improvement at week 24 (Hodges-Lehmann treatment estimate: seven meters). Median 6MWD improved with Orenitram at weeks 36 (13 meters) and 48 (21 meters) compared to placebo.

•Change in Borg dyspnea score and WHO functional class: When classified categorically as “improved,” “no change,” or “deteriorated,” participants in the Orenitram group exhibited a significantly positive shift in Borg dyspnea score and WHO functional class compared to placebo at weeks 24, 36, and 48.

•Change in NT-proBNP levels: NT-proBNP levels were significantly improved with Orenitram at weeks 24 and 36. Per the study protocol, NT-proBNP was not assessed at week 48.

•Change in combined 6MWD and Borg dyspnea score: Combined 6MWD and Borg dyspnea score was significantly improved with Orenitram when assessed at week 24 compared to placebo.

Sixty-eight percent of the initial FREEDOM-EV participants enrolled in an open-label extension (OLE) study to further assess Orenitram’s tolerability, efficacy, and survival. Participants randomized to placebo in the initial FREEDOM-EV study who initiated Orenitram therapy after clinical worsening and tolerated treatment through week 48 demonstrated 6MWD improvement of 84 meters (p0.0001), favorable shifts in functional class (p0.0001), and a reduction in NT-proBNP of 778 pg/mL (p=0.03), compared to OLE baseline. Modest trends toward benefit were also measured at week 48 for those initially assigned placebo who did not have clinical worsening. Patients initially assigned to the active Orenitram group who did not have clinical worsening and who continued Orenitram during the OLE study were stable at week 48. Mortality rates were similar between Orenitram and placebo groups at the end of randomized treatment. However, in participants for whom data are available (89 percent), Orenitram was associated with a 36 percent decreased risk of mortality compared with placebo at study closure (p=0.013). These mortality data are not reflected in the FDA-approved labeling because they include data accrued in the OLE study.

In 2020, we published the results of a retrospective study in which a competing therapy, selexipag, was associated with 67 percent higher PAH-associated healthcare costs on average, during the first six months of therapy, compared to Orenitram. Selexipag and Orenitram are the only FDA-approved oral prostacyclin-class therapies.

The studies that established efficacy included predominately patients with functional class II-III symptoms and etiologies of idiopathic or heritable PAH (66 percent) or PAH associated with connective tissue disease (26 percent). The most common side effects observed in our clinical studies were headache, nausea, and diarrhea. Orenitram is currently only approved in the United States.

Adcirca

Adcirca is a PDE-5 inhibitor, the active pharmaceutical ingredient of which is tadalafil. Tadalafil is also the active pharmaceutical ingredient in Cialis®, which is marketed by Eli Lilly and Company (Lilly) for the treatment of erectile dysfunction. We acquired the commercial rights to Adcirca for the treatment of PAH in the United States from Lilly in 2008. We sell Adcirca at prices established by Lilly. We recognized $30.0 million, $23.8 million, and $28.9 million in Adcirca net product sales, representing one percent of our total revenues for each of the years ended December 31, 2025, 2024, and 2023.

In 2009, the FDA approved Adcirca with a recommended dose of 40 mg, making it the only once-daily PDE-5 inhibitor for the treatment of PAH. Adcirca is indicated to improve exercise ability in patients with PAH. Studies establishing effectiveness included predominately patients with functional class II-III symptoms. Headaches were the most commonly reported side effect.

The current term of our Adcirca license agreement expires December 31, 2026.

Product to Treat Cancer — Unituxin

In March 2015, the FDA approved our biologics license application (BLA) for Unituxin, in combination with granulocyte-macrophage colony-stimulating factor, interleukin-2, and 13-cis-retinoic acid, for the treatment of patients with high-risk neuroblastoma (a rare form of pediatric cancer) who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Unituxin is a chimeric monoclonal antibody composed of a combination of mouse and human DNA that induces antibody-dependent cell-mediated cytotoxicity, a mechanism of cell-mediated immunity whereby the immune system actively targets a cell that has been bound by specific antibodies. Unituxin therapy is associated with severe side effects, including infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome. Unituxin has also been approved in Canada and Japan.

We recognized $226.8 million, $238.7 million, and $198.9 million in Unituxin net product sales, representing seven percent, eight percent, and nine percent of our total revenues for the years ended December 31, 2025, 2024, and 2023, respectively.

Research and Development

We focus our research and development efforts on the following pipeline programs. We also engage in a variety of additional research and development efforts, including efforts to develop new and improved devices to deliver our current commercial products and other small molecule therapies, some of which are intended for once-daily or as-needed administration, for a variety of pulmonary indications. In addition, we are developing technologies designed to increase the supply of transplantable organs and organ alternatives and improve outcomes for transplant recipients through xenotransplantation, regenerative medicine, and ex vivo lung perfusion.

Select Pipeline Programs

Nebulized Tyvaso — TETON studies

On September 2, 2025, we announced that the TETON 2 phase 3 study of Nebulized Tyvaso in patients with IPF met its primary efficacy endpoint of demonstrating improvement in absolute forced vital capacity (FVC) relative to placebo. Nebulized Tyvaso demonstrated superiority over placebo for the change in absolute FVC by 95.6 mL (Hodges-Lehmann estimate, p 0.0001) from baseline to week 52 in patients with IPF. Benefits of Nebulized Tyvaso were observed across all subgroups, such as use of background therapy (nintedanib, pirfenidone, or no background therapy), smoking status, and supplemental oxygen use.

Statistically significant improvements relative to placebo were also observed in most secondary endpoints, including time to first clinical worsening event, as well as changes from baseline to week 52 in percent predicted FVC, King’s Brief Interstitial Lung Disease quality of life questionnaire, and diffusion capacity of lungs for carbon monoxide. While not statistically significant, both time to first acute exacerbation of IPF and overall survival at week 52 trended in favor of Nebulized Tyvaso.

Treatment with Nebulized Tyvaso was well-tolerated, and the safety profile was consistent with previous Nebulized Tyvaso studies and known prostacyclin-related adverse events. No new safety signal was seen.

The TETON 2 study enrolled 597 patients and was conducted outside the United States and Canada. A second phase 3 study of Nebulized Tyvaso in IPF patients, called TETON 1, enrolled 598 patients in the United States and Canada. We intend to use the data from both the TETON 2 study and the ongoing TETON 1 study to support a supplemental NDA to the FDA to add IPF to the labeled indications for Nebulized Tyvaso. Data readout from TETON 1 is expected late in the first quarter, or early in the second quarter, of 2026.

The TETON 1 and TETON 2 studies were prompted by data from the INCREASE study of Nebulized Tyvaso for the treatment of PH-ILD, which demonstrated in a post-hoc analysis that treatment with Nebulized Tyvaso resulted in significant improvements in percent predicted FVC at weeks 8 and 16, with subjects having an underlying etiology of IPF showing the greatest improvement (week 8: 2.5 percent; p=0.038 and week 16: 3.5 percent; p=0.015). Further, OLE data published in 2023 showed that these improvements in FVC were sustained for at least 64 weeks. For those patients who received placebo during the INCREASE study, marked improvements in FVC were observed following transition to Nebulized Tyvaso during the OLE study. These data points, combined with substantial preclinical evidence of antifibrotic activity of treprostinil and the results of the TETON 2 study, 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.

We are also conducting a phase 3 study of Nebulized Tyvaso called TETON PPF for the treatment of progressive pulmonary fibrosis (PPF); we enrolled the first patient in TETON PPF in October 2023. The primary endpoint of the TETON PPF study is the change in absolute FVC from baseline to week 52. The TETON PPF study was also prompted by a post-hoc analysis of data from the INCREASE study. PPF is a group of ILD conditions that exhibit progressive, self-sustaining fibrosis, and a similar disease course to IPF. PPF includes idiopathic interstitial pneumonias, autoimmune ILDs, chronic fibrosing hypersensitivity pneumonitis, and fibrotic ILDs related to environmental/occupational exposure. We are targeting enrollment of 698 patients in the TETON PPF study. We believe the U.S. PPF population is similar in size to the IPF population, although it could be larger as some estimates indicate the U.S. population exceeds 180,000 patients.

We and our distributors will also consider seeking amendments to the marketing authorizations for Nebulized Tyvaso in other countries where it is approved, to include IPF and/or PPF indications, and we will also consider seeking approval of Nebulized Tyvaso for these indications in countries where it is not yet approved. Both the FDA and the European Medicines Agency have granted orphan designation for treprostinil to treat IPF, but not for PPF.

Treprostinil SMI

We are developing a version of inhaled treprostinil that will be a drug-device combination consisting of treprostinil solution and a device known as a soft mist inhaler (SMI). SMI devices are propellant-free, hand-held mechanical devices that deliver an aerosol cloud of medication via a single breath. SMI devices would be more convenient for our patients than the current Tyvaso nebulizer, which requires several breaths using a much larger device that needs electricity. SMI devices are pocket-sized and disposable, and would be delivered pre-filled with drug product, ready to use, without the need to fill it every day like a nebulizer. SMI devices could also provide a favorable adverse event profile compared to dry powder inhalers. We are targeting the same indications for which Nebulized Tyvaso is already approved (PAH and PH-ILD), as well as those for which we plan to seek FDA approval in the future (IPF and PPF). Additionally, we are planning a phase 2 study of treprostinil SMI to treat patients with PH-COPD.

Ralinepag

Ralinepag is a next-generation, once-daily, oral, extended-release, titratable, selective, and potent prostacyclin receptor agonist that we are developing for the treatment of PAH. A phase 2 study of an immediate-release formulation of ralinepag in 61 PAH patients (40 patients on active ralinepag, 21 on placebo) met its primary endpoint, showing a 29.8 percent reduction (p=0.03) in median pulmonary vascular resistance (PVR, the force or resistance that blood encounters as it flows through the blood vessels in the lungs) after 22 weeks of treatment with ralinepag compared with placebo. 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. Moreover, two years after entering the OLE study, the study showed that ralinepag improved the ability to exercise as the 6MWD significantly increased by a mean of 36.3 meters (p=0.004), and over 85 percent of patients remained stable in their functional class. Additionally, hemodynamic measures (metrics to measure how well the heart is working) taken either one or two years after entering the OLE study demonstrated significant improvements (p=0.05) in both median PVR and mean pulmonary arterial pressure (the pressure in the blood vessels connecting the heart).

In June 2025, we concluded enrollment of the ADVANCE OUTCOMES study, which is a phase 3, event-driven clinical trial 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. We continued accruing clinical worsening events in this study through the end of 2025, and plan to release topline data from the study late in the first quarter, or early in the second quarter, of 2026.

If approved and launched, we expect ralinepag’s once-daily dosing profile to position it favorably compared with Uptravi (selexipag), which is a twice-daily IP-receptor agonist marketed by Johnson & Johnson for the treatment of PAH. In 2025, Johnson & Johnson reported global sales of Uptravi of over $1.9 billion, including over $1.5 billion in U.S. sales, reflecting a growth rate of approximately 5 percent over 2024.

Assuming the ADVANCE OUTCOMES study is successful, we plan to develop an oral triple-combination therapy consisting of ralinepag, an endothelin receptor antagonist, and a PDE-5 inhibitor.

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. Unfortunately, the number of usable, donated organs available for transplantation has not grown significantly over the past half century, while the need has soared. Our long-term goals are aimed at addressing this shortage. 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. 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, and ex vivo lung perfusion.

While we continue to develop and commercialize therapies for rare and life-threatening conditions, we view manufactured organs and organ alternatives as complementary solutions for a broad array of diseases, many of which (such as PAH and PH-ILD) have proven incurable to date despite the availability of pharmaceutical and biologic therapies. For this reason, we included the development of “technologies that expand the availability of transplantable organs” as part of our express public benefit purpose when we converted United Therapeutics to a PBC in 2021.

Xenotransplantation

Our xenotransplantation program includes three development-stage organ products known as “xenografts”, which are intended to be transplanted from gene-edited pigs into humans.

The UKidney™ is a development-stage kidney from a pig with ten gene edits to support organ functioning in the human body. Six human genes were added to the pig genome to facilitate immune acceptance of the organ, while four genes were inactivated: three that contribute to porcine organ rejection in humans and one that can cause organ growth beyond what is normal for humans. The UHeart™ is a heart from the same pig with ten gene edits.

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. 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. 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. Meat from GalSafe pigs is currently being provided to 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.

Johns Hopkins University (JHU), New York University (NYU), the University of Alabama at Birmingham (UAB), and the University of Maryland, Baltimore (UMB) performed preclinical testing of our porcine xenografts in animal models. In addition, we worked with NYU and UAB to employ innovative preclinical human models to obtain insights into how xenografts function inside the human body.

In January 2025, the FDA cleared our Investigational New Drug application (IND) related to the EXPAND study of our UKidney product. This study is expected to enroll an initial cohort of six end-stage renal disease (ESRD) patients, expanding to up to 50 participants, and we intend to use the results of this study to support a BLA with the FDA. This study is designed as a combination phase 1/2/3 trial (sometimes referred to as a “phaseless” study) to evaluate safety and efficacy seamlessly without moving through separate phase 1, phase 2, and phase 3 studies that are typically associated with conventional drug approvals. The first transplant in this study occurred in the fourth quarter of 2025, and the study is ongoing.

In July 2025, we submitted an IND to the FDA related to our anticipated EXTEND clinical study of our UThymoKidney product. In August 2025, the FDA cleared this IND, enabling us to commence this study, which we expect will be similar in size and scope to the EXPAND study described above.

In February 2024, we completed a designated pathogen-free (DPF) facility in Virginia. We expect this DPF facility to supply xenografts compliant with FDA current Good Manufacturing Practices (cGMP) for human clinical trials, with a target capacity of up to 125 organs per year. We are constructing two additional DPF facilities in Minnesota and Texas. While we believe these DPF facilities will be capable of producing organs for commercial use, we are also planning to build additional and potentially larger cGMP DPF facilities for commercial use. 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.

Additional key accomplishments in our xenotransplantation program include the following:

•First Successful Xenotransplants of Porcine Hearts. University of Maryland School of Medicine (UMSOM) surgeons transplanted UHearts into two living human patients. Each of these procedures were authorized by the FDA on a single-patient, expanded access (also called “compassionate use”) basis, and marked the first known examples of transplanting whole organs from gene-edited pigs to humans. 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 2022, data from this procedure were published in the New England Journal of Medicine. The second patient, who received a xenotransplant in September 2023, survived for approximately six weeks with the UHeart. We and our collaborators continue to evaluate data from these human transplants.

•First Successful Transplantation of Porcine Thymokidney. In April 2024, surgeons at NYU Langone Health transplanted a UThymoKidney into a living patient under an FDA authorization for compassionate use. The patient was suffering from heart and kidney failure, and received a left ventricular assist device to stabilize heart function prior to the UThymoKidney transplant. The procedure marked the first known transplantation of a thymokidney into a human, the first known transplantation of a gene-edited porcine kidney into a human using only FDA-cleared immunosuppression drugs, and the first known procedure combining the use of a heart pump with a transplanted porcine xenokidney. After 47 days, surgeons electively removed the UThymoKidney and returned the patient to dialysis. According to NYU Langone Health, the UThymoKidney had sustained significant injury from episodes of insufficient blood flow due to reduced blood pressure generated by the heart pump and, on balance, was no longer contributing enough to justify continuing the patient’s immunosuppression regimen. NYU Langone Health noted that a biopsy of the UThymoKidney did not show signs of rejection.

•Second Successful Transplantation of a Porcine Kidney. In November 2024, surgeons at NYU Langone Health transplanted a UKidney into a living patient under an FDA authorization for compassionate use. In March 2025, the patient developed an infection unrelated to the transplant that led to the reduction of immunosuppression drugs and the rejection of the organ. As a result, the UKidney was removed and the patient returned to dialysis. The UKidney performed well for over four months.

•Successful UKidney and UHeart Tests in Preclinical Human Models. In 2021, surgeons at NYU and UAB tested UThymoKidneys and UKidneys from our gene-edited pigs in brain-dead organ donors maintained on artificial support, providing preclinical evidence that gene-edited pig organs could transcend the most proximate immunological barriers to xenotransplantation. 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. Results of the UAB experiments were published in the American Journal of Transplantation in January 2022 and the Journal of Clinical Investigation in January 2024, and results of the NYU experiments were published in the New England Journal of Medicine in May 2022.

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.

In September 2023, NYU surgeons completed a 61-day study of a UThymoKidney in a brain-dead organ donor maintained on artificial support. At the time, this experiment marked the longest documented case of a xenotransplanted organ functioning in a human body.

Regenerative Medicine

•Miromatrix. In December 2023, we acquired Miromatrix Medical Inc. (Miromatrix), a company based in Minnesota focused on the development of new technologies for generating manufactured kidneys and liver alternatives composed of human primary cells. The development-stage Miromatrix external liver assist product, called miroliverELAP®, uses a decellularized porcine liver matrix that has been seeded with human-derived cells and an extracorporeal blood circuit to maintain liver support in patients experiencing acute liver failure. Miromatrix first used its decellularization technology to successfully develop two acellular products, MiroMesh® and MiroDerm®, which received FDA 510(k) clearance for hernia repair and wound care applications, respectively, and which were later spun off by Miromatrix. In January 2026 we announced that Miromatrix completed a phase 1 study of miroliverELAP in patients with acute liver failure. This study, which was the first human clinical trial of a manufactured organ alternative, met its primary endpoint. Miromatrix is planning to commence a phase 2 study. 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 made with cells from a human donor other than the recipient (also called “allogeneic” cells), requiring the use of standard immunosuppression protocols. Future versions may be based on the patient’s own cells (known as “autologous” cells), reducing or eliminating the need for immunosuppression drugs.

•ULobe™. The ULobe is a development-stage engineered lung lobe alternative made using a porcine lung scaffold that is decellularized and then re-cellularized with allogeneic human cells. In 2025, our Regenerative Medicine Laboratory in Research Triangle Park, North Carolina (RTP) produced 830 decellularized lung scaffolds, 345 recellularized lungs, and 1.65 trillion human cells for use in recellularization.

•ULung™. The ULung is a development-stage engineered lung alternative composed of a three-dimensional (3D) printed lung scaffold cellularized with either allogeneic or autologous human lung cells, with the goal of reducing or eliminating the need for immunosuppression. 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. 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. In October 2023, we completed the acquisition of IVIVA Medical, Inc. (IVIVA), a preclinical stage company based in Massachusetts, focused on bio-artificial manufactured kidney alternative products. IVIVA’s preclinical implantable kidney alternative product uses autologous cells to mimic important physiological functions of native kidneys in recipients to support their native kidney function without the need for immunosuppression. The product is designed to replace the need for external kidney dialysis.

Ex Vivo Lung Perfusion

Our ex vivo lung perfusion (EVLP) program uses the first FDA-approved acellular EVLP technology on the market, the XVIVO Perfusion System (XPS™) with Steen Solution™ Perfusate, to offer the only commercially-available centralized EVLP service in the United States. EVLP technology increases the number of transplantable lungs by giving surgeons the ability to assess the function of donor lungs to determine if the lungs are suitable for transplantation. This allows for the transplantation of lungs that would have otherwise not been transplanted. Centralized EVLP services make EVLP available to small and large transplant centers and remove barriers to the transplantation process to optimize organ utilization and increase the supply of transplantable lungs.

Our wholly-owned subsidiary, Lung Bioengineering Inc., provides commercial EVLP services on a fee-for-service basis to transplant centers through dedicated facilities located in Silver Spring, Maryland and Jacksonville, Florida, using the XPS System. In 2024, Lung Bioengineering completed a registrational study of another centralized EVLP technology called the Centralized Lung Evaluation System (CLES) and submitted a premarket approval application to the FDA in September 2024 for commercial approval of CLES, which is under review by the FDA.

Over 730 patients have received lung transplants following use of our centralized EVLP service.

Sustainable Delivery of Organs and Organ Alternatives

Together with our work on therapeutic interventions, we are working with third parties to develop scalable technologies to efficiently deliver an unlimited supply of manufactured organs and organ alternatives to transplant centers and waiting patients, while minimizing environmental impact. 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.

Beginning in 2017, we entered into a series of agreements with BETA Technologies, Inc. to support the development of all-electric aircraft to help us meet our future distribution requirements for manufactured organs and organ alternatives. In October 2021, we successfully completed the first-ever drone delivery of a human lung for transplant at Toronto General Hospital, demonstrating the feasibility of our goal of delivering our manufactured organs and organ alternatives with zero carbon footprint aircraft. In October 2024, we entered into a collaboration agreement with Robinson Helicopter Company to support our efforts to develop and certify zero-emission, hydrogen-electric powered helicopters based on Robinson’s R44 and R66 helicopter models. In March 2025, we completed what we believe was the world’s first successful test flight of a piloted hydrogen-electric powered helicopter at our test and development facility located in Quebec.

Sales and Marketing

Our marketing strategy for our commercial PAH and PH-ILD products is to use our sales and marketing teams to reach out to the prescriber community to: (1) increase PAH and PH-ILD awareness; (2) increase understanding of the progressive nature of PAH and the importance of early treatment; (3) communicate the increased risks when ILD patients develop PH-ILD; and (4) increase awareness of our commercial products and how they fit into the various stages of disease progression and treatment.

Distribution of Commercial Products

United States Distribution of Tyvaso DPI, Nebulized Tyvaso, Remodulin, Remunity and RemunityPRO Pumps, Orenitram, and Unituxin

We distribute Tyvaso DPI, Nebulized Tyvaso, Remodulin, the Remunity and RemunityPRO Pumps, and Orenitram in the United States through two contracted specialty pharmaceutical distributors: Accredo Health Group, Inc. and its affiliates (Accredo) and Caremark, L.L.C. (CVS Specialty). These 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. If any of our distribution agreements expire or terminate, we may, under certain circumstances, be required to repurchase any unsold inventory held by our distributors.

These specialty pharmaceutical distributors are responsible for assisting patients with obtaining reimbursement for the cost of our treprostinil-based products and providing other support services. Under our distribution agreements, we sell each of our treprostinil-based products to these distributors at a transfer price that we establish. We have also established patient assistance programs in the United States, which provide our treprostinil-based products to eligible uninsured or under-insured patients at no charge. Accredo and CVS Specialty assist us with the administration of these programs.

We distribute Unituxin in the United States through an exclusive distribution agreement with Cencora Global Procurement Ltd (Cencora). Under this agreement, we sell Unituxin to Cencora at a transfer price that we establish, and we pay Cencora fees for services provided in connection with the distribution and support of Unituxin.

To the extent we increase the price of any of these products, increases are typically in the single-digit percentages per year.

United States Distribution of Adcirca

Under our manufacturing and supply agreement with Lilly, Lilly manufactures and distributes Adcirca on our behalf through its wholesaler network in the same manner that it distributes its own pharmaceutical products. Under the terms of this agreement, we take title to Adcirca upon completion of its manufacture by Lilly. Adcirca is shipped to customers in accordance with purchase orders received by Lilly. Upon shipment, Lilly sends an invoice and collects the amount due from the customer subject to customary discounts and rebates, if any. Although Lilly provides these services on our behalf, we maintain the risk of loss as it pertains to inventory, product returns, and non-payment of invoices. The manufacturing and supply agreement will continue in effect until the December 31, 2026 expiration or earlier termination of our license agreement for Adcirca. Lilly retains authority under the license agreement for all regulatory activities with respect to Adcirca as well as its retail pricing.

International Distribution of Tyvaso DPI, Nebulized Tyvaso, Remodulin, Orenitram, and Unituxin

We currently sell Remodulin outside the United States to various distributors, each of which has exclusive distribution rights in one or more countries within Europe, the Middle East, Asia, and South and Central America. Our primary distributor outside the United States is Grupo Ferrer Internacional, S.A. (Ferrer), which holds Remodulin marketing authorization rights in many of these territories. We also sell Nebulized Tyvaso exclusively through Mochida Pharmaceutical Co., Ltd. (Mochida), in Japan, where the product was approved to treat PAH in late 2022, and to treat PH-ILD in 2024. In addition, we sell Nebulized Tyvaso commercially to distributors that have exclusive distribution rights in various countries in Asia, the Middle East, and Latin America, where it is approved for PAH and/or PH-ILD. We also distribute Remodulin and Unituxin in Canada through a specialty pharmaceutical wholesaler. In some of the markets where we are not licensed to market Remodulin, Remodulin is available, but not marketed, on a named patient basis in which therapies are approved for individual patients by a national medical review board, hospital, or health plan on a case-by-case basis. Similar named-patient programs are also available for Nebulized Tyvaso in certain countries. We entered into exclusive agreements with Ferrer to distribute Orenitram and Nebulized Tyvaso in the territories where it also has distribution rights for Remodulin. Feedback from the EMA indicated that approval of either Orenitram or Nebulized Tyvaso would require another large clinical trial of the applicable product. As a result, we have terminated our contract with Ferrer concerning Orenitram. We plan to revisit seeking EMA approval for Nebulized Tyvaso if the TETON program is successful. In 2025, Ferrer submitted a marketing authorisation application (MAA) to the U.K. Medicines and Healthcare products Regulatory Authority (MHRA) seeking approval for Nebulized Tyvaso to treat PH-ILD. We distribute Unituxin in Japan exclusively through Ohara Pharmaceutical Co., Ltd., which obtained Japanese marketing authorization during the second quarter of 2021. Tyvaso DPI is not yet approved or distributed in any countries outside the United States.

Patents and Other Proprietary Rights, Strategic Licenses, and Market Exclusivity

Our success depends in part on our ability to obtain and maintain patent protection for our products, preserve trade secrets, prevent third parties from infringing upon our proprietary rights, and operate without infringing upon the proprietary rights of others in the United States and worldwide. Many of these proprietary rights stem from licenses and other strategic relationships with third parties. In addition to intellectual property rights, U.S. and international regulatory authorities often provide periods of market exclusivity for manufacturers of biopharmaceutical products.

Patents provide the owner with a right to exclude others from practicing an invention. Patents may cover the active ingredients, uses, formulations, doses, administrations, delivery mechanisms, manufacturing processes, and other aspects of a product. The period of patent protection for any given product generally depends on the expiration date of various patents and may differ from country to country according to the type of patents, the scope of coverage, and the remedies for infringement available in a country. Most of our commercial products and investigational products are protected by patents that expire on varying dates.

Significant legal questions exist concerning the extent and scope of patent protection for biopharmaceutical products and processes in the United States and elsewhere. Accordingly, there is no certainty that patent applications owned or licensed by us will be issued as patents, or that our issued patents will afford meaningful protection against competitors. Once issued, patents are subject to challenge through both administrative and judicial proceedings in the United States and other countries. Such proceedings include re-examinations, inter partes reviews (IPR), post-grant reviews, and interference proceedings before the U.S. Patent and Trademark Office, as well as opposition proceedings before the European Patent Office. Litigation may be required to enforce, defend, or obtain our patent and other intellectual property rights. Any administrative proceeding or litigation could require a significant commitment of our resources and, depending on outcome, could adversely affect the scope, validity, or enforceability of certain of our patent or other proprietary rights.

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. 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.

In addition to the treprostinil patents noted above, we have other patents specific to our individual treprostinil-based products, including the following:

•Tyvaso DPI. We have two Orange Book-listed U.S. patents that we license from MannKind directed to the composition of Tyvaso DPI drug product, which expire in 2030 and 2035. We have another issued U.S. patent listed in the Orange Book directed to a method of improving exercise capacity in patients with PH-ILD expiring in 2042. We also have an issued U.S. patent listed in the Orange Book directed to a method of treating pulmonary hypertension using inhaled treprostinil expiring in 2027. 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. 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. This patent is also listed in the Orange Book. Additionally, we have been granted a patent directed to a method of improving exercise capacity in PH-ILD patients, which expires in 2042.

•Remodulin. We have been granted three U.S. patents covering an improved diluent for Remodulin, which expire in 2028 and 2029. All three of these patents are listed in the Orange Book.

•Orenitram. Our U.S. patents for Orenitram orally administered formulations, controlled moisture storage and manufacturing methods, as well as those covering controlled release formulations licensed to us by Supernus Pharmaceuticals Inc. (Supernus). These patents will expire in the United States between 2026 and 2031.

We have international counterparts to many of the patents discussed above and additional pending U.S. and international patent applications related to Tyvaso DPI, Nebulized Tyvaso, Remodulin, and Orenitram.

Orange Book

In seeking approval of a drug through an NDA or upon issuance of new patents following approval of an NDA, applicants are required to submit to the FDA each patent that has claims covering the applicant’s product or a method of using the product. Each of the patents submitted is then published in the Orange Book. 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 2027 to 2042. Nebulized Tyvaso currently has six unexpired Orange Book-listed patents expiring at various dates from 2027 to 2042. 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. 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 exclusivity period covered both Nebulized Tyvaso and Tyvaso DPI for PH-ILD, and expired in March 2024. Additionally, the FDA determined in August 2024 that we were entitled to a period of exclusivity for Nebulized Tyvaso and Tyvaso DPI based on a clinical trial conducted to obtain approval for a PH-ILD indication; this exclusivity expired on May 23, 2025. In 2004, the European Commission designated Nebulized Tyvaso an orphan medicinal product for the treatment of both PAH and chronic thromboembolic pulmonary hypertension, which would confer a ten-year exclusivity period commencing if and when we obtain marketing approval. In December 2020, the FDA granted orphan designation for treprostinil for the treatment of IPF. Thus, if we obtain FDA approval to update the Tyvaso DPI and/or Nebulized Tyvaso labeling to include an IPF indication, then the FDA should grant seven-year orphan drug exclusivity for this new indication. The EMA has also granted orphan drug designation for treprostinil to treat IPF.

•Remodulin. Regulatory exclusivity for Remodulin in the United States and Europe has expired.

•Orenitram. In November 2019, following approval of our supplemental NDA to reflect the FREEDOM-EV results in the Orenitram label, the FDA granted orphan exclusivity for the new indication that Orenitram delays disease progression in PAH patients. This exclusivity expires in October 2026.

Supernus License

In 2006, we entered into an exclusive license agreement with Supernus to use certain of its technologies in manufacturing Orenitram. Under the agreement, we paid Supernus certain amounts upon the achievement of specified milestones based on the development and commercial launch of Orenitram for PAH, and we would be obligated to make additional milestone payments if we develop Orenitram for a second indication. In addition, the agreement provides that we will pay a single-digit percentage royalty based on net worldwide sales. The term of this royalty expires during the fourth quarter of 2026.

Manufactured Organ and Organ Alternative Proprietary Rights

We have a large portfolio of pending patent applications and issued patents that could protect our proprietary rights in our manufactured organs and organ alternative products. We own patents, and have licensed rights under third-party patents, covering various aspects of these products; we do not view any one patent or group of patents as critical. For example, we have over 150 pending patent applications and multiple issued patents covering various aspects of our 3D organ alternative bioprinting program, and we have exclusively licensed an extensive 3D printing patent portfolio from 3D Systems for use in the field of manufacturing solid organ alternatives. Our xenotransplantation patent portfolio includes over 150 pending applications and issued patents, including nearly one hundred issued patents in the U.S. and abroad. Our regenerative medicine patent portfolio includes over 300 pending applications and issued patents.

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. In addition, we may rely on trade secret protection for certain aspects of our manufactured organ and organ alternative programs.

Generic Competition and Challenges to our Intellectual Property Rights

Remodulin—Generic Competition

We settled litigation with Sandoz Inc. (Sandoz) related to its abbreviated new drug application (ANDA) seeking FDA approval to market a generic version of Remodulin and in March 2019, Sandoz announced the availability of its generic product in the United States. We have also entered into similar settlement agreements with other generic companies, some of which have also launched sales of generic versions of Remodulin. Through December 31, 2025, we have seen limited erosion of Remodulin sales as a result of generic treprostinil competition in the United States. We are currently engaged in litigation with

Sandoz and its marketing partner, RareGen, LLC (RareGen) (now a subsidiary of Liquidia Corporation, the parent company of Liquidia Technologies, Inc. (Liquidia)), related to the infusion devices used to administer Remodulin subcutaneously. We understand that generic treprostinil was initially launched by Sandoz/RareGen for use only by intravenous infusion. In May 2021, Sandoz/Liquidia Corporation announced that Sandoz’s generic treprostinil was made available for subcutaneous use, following FDA clearance of a cartridge that can administer the product via the MS-3 pump. In addition, Liquidia has announced it is developing a new subcutaneous infusion system for its generic treprostinil product. See Note 14—Litigation, to our consolidated financial statements included in this Report.

Regulatory authorities in various European countries began approving generic versions of Remodulin in 2018, followed by pricing approvals and commercial launches in most of these countries in 2019 and 2020. As a result, our international Remodulin revenues have decreased compared to the period prior to generic launch, due to increased competition and a reduction in our contractual transfer price for Remodulin sold by certain international distributors for sales in countries in which the pricing of Remodulin is impacted by the generic competition.

Nebulized Tyvaso and Orenitram—Potential Future Generic Competition

We settled litigation with Watson Laboratories, Inc. (Watson) related to its ANDA seeking FDA approval to market a generic version of Nebulized Tyvaso before the expiration of certain of our U.S. patents. Under the settlement, Watson was permitted to market its generic version of Nebulized Tyvaso in the United States as early as January 2026, although, to date, they have not received FDA approval to do so.

We also settled litigation with Actavis Laboratories FL, Inc. (Actavis) and ANI Pharmaceuticals, Inc. (ANI) related to their ANDAs seeking FDA approval to market generic versions of Orenitram before the expiration of certain of our U.S. patents. Under the settlement agreements, Actavis and ANI can market their generic versions of Orenitram in the United States beginning in June 2027 and December 2027, respectively, although either or both of them may be permitted to enter the market earlier under certain circumstances.

Competition from these generic companies could reduce our net product sales and profits. See Note 14—Litigation, to our consolidated financial statements included in this Report.

Liquidia—Yutrepia

In May 2025, Liquidia obtained final FDA approval to market Yutrepia®, a dry powder formulation of treprostinil for inhalation, to treat PAH and PH-ILD. Liquidia announced that it launched sales of Yutrepia in June 2025. The Yutrepia NDA was submitted under the 505(b)(2) regulatory pathway with Nebulized Tyvaso as the reference listed drug. Yutrepia competes directly with Tyvaso DPI, Nebulized Tyvaso, and our other treprostinil-based products.

We are engaged in patent litigation with Liquidia concerning Yutrepia. Specifically, we allege that Yutrepia infringes a patent we own covering the treatment of PH-ILD to improve exercise capacity in patients suffering from PH-ILD by inhaling treprostinil at specific dosages. If we are successful in this litigation, we believe Liquidia will be required to remove PH-ILD as a labeled indication for Yutrepia until the expiration of our patent in February 2042. We are also engaged in litigation with Liquidia alleging trade secret misappropriation. In this case, we allege that a former executive of ours misappropriated trade secrets related to Tyvaso when he utilized them as an executive of Liquidia to aid in the development of Yutrepia. Finally, we are engaged in separate litigation against Liquidia alleging that Yutrepia infringes a patent that claims a method of treating pulmonary hypertension using inhaled treprostinil delivered in a specified dosage using a specified dosage regimen. This patent expires in May 2027.

Liquidia has also sued us, alleging infringement of a patent with claims directed to the treatment of pulmonary hypertension by administering specified amounts of treprostinil via a dry powder inhaler in a specified number of breaths. That case is currently stayed pending developments in the trade secret misappropriation litigation described above.

For further details regarding these and other litigation matters involving Liquidia and Yutrepia, please see Note 14—Litigation, to our consolidated financial statements.

General

We intend to vigorously enforce our intellectual property rights related to our products. However, we may not prevail in defending our patent rights, and additional challenges from other ANDA filers or other challengers may surface with respect to our products. Our patents could be invalidated, found unenforceable, or found not to cover one or more generic forms of our products. If any ANDA filer or filer of a 505(b)(2) NDA for a branded treprostinil product were to receive approval to sell its treprostinil product and/or prevail in any patent litigation, our affected product(s) would become subject to increased competition. Patent expiration, patent litigation, and competition from generic or other branded treprostinil manufacturers could have a significant, adverse impact on our treprostinil-based product revenues, our profits, and our stock price. These potential effects are inherently difficult to predict. For additional discussion, see the risk factor entitled, Our intellectual property rights may not effectively deter competitors from developing competing products that, if successful, could have a material adverse effect on our revenues and profits, contained in Part I, Item 1A—Risk Factors included in this Report.

Adcirca License Agreement

In 2008, Lilly granted us an exclusive license to develop, market, promote, and commercialize Adcirca for the treatment of pulmonary hypertension in the United States. We agreed to pay Lilly royalties based on our net product sales of Adcirca. Lilly retained the exclusive rights to develop, manufacture, and commercialize pharmaceutical products containing tadalafil, the active pharmaceutical ingredient in Adcirca, for the treatment of pulmonary hypertension outside of the United States and for the treatment of other diseases worldwide. Lilly retained authority for all regulatory activities with respect to Adcirca and for setting the wholesale price of Adcirca. In May 2017, we amended our Adcirca license agreement with Lilly to clarify and extend the term of the agreement and to amend the economic terms of the agreement following a patent expiry in November 2017. As a result, we are required to make milestone payments to Lilly equal to $325,000 for each $1.0 million in net product sales, plus a royalty equal to ten percent of our net product sales. The current term of our Adcirca license agreement expires December 31, 2026. Following expiration of the agreement, we will remain obligated to refund the purchase price of any Adcirca that we previously sold to distributors that expires unsold. For additional discussion, see our Adcirca product description included in Part I, Item 1—Business Overview—Products to Treat Pulmonary Arterial Hypertension.

We also agreed to purchase Adcirca at a fixed manufacturing cost. The agreement provides a mechanism, generally related to the increase in the national cost of pharmaceutical manufacturing, pursuant to which Lilly may raise the manufacturing cost of Adcirca.

Unituxin Proprietary Rights and Regulatory Exclusivity

Approval of our BLA for Unituxin conferred a 12-year data exclusivity period through March 2027, during which the FDA may not approve a biosimilar for Unituxin. Our orphan drug exclusivity in the United States for Unituxin expired in March 2022. Under a non-exclusive license agreement with The Scripps Research Institute, we pay a royalty of one percent of Unituxin net product sales. We have no patents covering the Unituxin drug product.

DEKA Agreements

In December 2014, we entered into an exclusive agreement with DEKA to develop a semi-disposable system for subcutaneous delivery of Remodulin, which we refer to as the Remunity and RemunityPRO Pumps. Our agreement with DEKA expires on the last to occur of 25 years from the first product launch under the agreement, or upon the expiration of the last valid claim of a patent licensed from DEKA under the agreement that covers the pumps. Under the terms of the agreement, we funded the development costs related to the Remunity and RemunityPRO Pumps and will continue to fund any further development costs associated with new versions. We pay product fees and a single-digit royalty to DEKA based on commercial sales of the Remunity and RemunityPRO Pumps, and the Remodulin drug product sold for use with the system. Either party may terminate the agreement immediately upon a material breach by the other party that is uncured following the relevant cure period, or in the event of the other party’s bankruptcy or insolvency. In November 2019, we entered into a supply agreement with an affiliate of DEKA to manufacture and supply the Remunity Pump, and later amended it to provide for manufacture and supply of the RemunityPRO Pump. Under this supply agreement, we are responsible for all costs associated with manufacturing the Remunity and RemunityPRO Pumps. The Remunity and RemunityPRO Pumps are covered by issued patents and pending patent applications both in the U.S. and other countries. The expiration dates of currently issued U.S. patents range from 2027 through 2033.

Tyvaso DPI and the MannKind Agreement

In September 2018, we entered into a worldwide, exclusive license and collaboration agreement with MannKind for the development and commercialization of Tyvaso DPI for the treatment of PAH. The agreement became effective on October 15, 2018.

Under our agreement with MannKind, we are responsible for global development, regulatory, and commercial activities related to Tyvaso DPI, and we share manufacturing responsibilities with MannKind. The agreement also requires us to pay MannKind a ten percent royalty on our net sales of Tyvaso DPI, subject to certain reductions. In addition, we have the option, in our sole discretion, to expand the license to include other active ingredients for the treatment of pulmonary hypertension. 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. In August 2025, we exercised this option and amended our agreement with MannKind to include development and commercialization of a second investigational molecule utilizing MannKind’s dry powder technology.

In December 2023, MannKind entered into a royalty purchase agreement with Sagard Healthcare Funding Partners Borrowers 2 SPE, LP, with our consent, to sell ten percent of the royalties payable under the license agreement (i.e., one percentage point of the ten percent royalty) in exchange for $150.0 million up-front, plus up to an additional $50.0 million if net sales of Tyvaso DPI meet certain thresholds. Based on the up-front purchase price alone, the implied net present value of future Tyvaso DPI net revenues at the time of the transaction was $15.0 billion.

Under our license agreement with MannKind, we have an exclusive license to a variety of granted and pending patents and patent applications related to treprostinil inhalation powder and the Dreamboat device, including multiple patent families covering the U.S. and other major market countries. These patents cover drug formulation, devices and device components, and manufacturing processes and intermediates. For additional detail concerning these patents, see Tyvaso DPI, Nebulized Tyvaso, Remodulin, and Orenitram Proprietary Rights above.

In August 2021 we entered into a commercial supply agreement with MannKind (as amended, the Supply Agreement). Pursuant to the Supply Agreement, MannKind is responsible for manufacturing and supplying Tyvaso DPI to us. Unless earlier terminated, the initial term of the Supply Agreement continues until December 31, 2031, and will thereafter be renewed automatically for additional, successive two-year terms unless we give 24 months’ written notice of non-renewal, or MannKind gives 48 months’ written notice of non-renewal, prior to the end of the initial term or any additional renewal term. In addition, each party has customary termination rights, including termination for the other party’s material breach that is not cured within a specific timeframe or in the event of liquidation, bankruptcy, or insolvency of the other party.

Ralinepag and the Arena Agreement

On November 15, 2018, we entered into an exclusive license agreement with Arena Pharmaceuticals, Inc. (Arena) related to ralinepag. On January 24, 2019, in connection with the closing of the transactions contemplated by the license agreement: (1) Arena granted to us perpetual, irrevocable, and exclusive rights throughout the universe to develop, manufacture, and commercialize ralinepag; (2) Arena transferred to us certain other assets related to ralinepag, including, among others, related domain names and trademarks, permits, certain contracts, inventory, regulatory documentation, IND No. 109021 (related to ralinepag), and non-clinical, preclinical, and clinical trial data; and (3) we assumed certain limited liabilities from Arena, including, among others, all obligations arising after the closing under the assumed contracts and the IND described above. Under our license agreement, we are obligated to pay Arena: (1) a one-time payment of $250.0 million for the first, if any, marketing approval we receive in the United States for an inhaled version of ralinepag to treat PAH; (2) a one-time payment of $150.0 million for the first, if any, marketing approval we receive in any of Japan, France, Italy, the United Kingdom, Spain, or Germany for an oral version of ralinepag to treat any indication; and (3) low double-digit, tiered royalties on net sales of any pharmaceutical product containing ralinepag as an active ingredient, subject to certain adjustments for third-party license payments. 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. Based on potential patent term extensions and additional patent filings, we believe that U.S. patent protection for ralinepag will likely last through at least the mid-2030s.

Other

We are party to various other license agreements related to therapies and technologies under development. These license agreements require us to make payments based on a percentage of sales if we are successful in commercially developing these therapies, and may require other payments upon the achievement of certain milestones.

Manufacturing and Supply

We synthesize treprostinil, the active ingredient in Tyvaso DPI, Nebulized Tyvaso, and Remodulin, and treprostinil diolamine, the active ingredient in Orenitram, at our facility in Silver Spring, Maryland. We produce dinutuximab, the active ingredient in Unituxin, at our Silver Spring facility. We manufacture drug product for Nebulized Tyvaso, Remodulin, and Unituxin at our Silver Spring facility. We manufacture Orenitram drug product, and we package, warehouse, and distribute Tyvaso DPI, Nebulized Tyvaso, Remodulin, Orenitram, and Unituxin, at our facilities in RTP.

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. For example, Simtra BioPharma Solutions (formerly known as Baxter Pharmaceutical Solutions, LLC) is approved by the FDA, the EMA, and various other international regulatory agencies to manufacture Remodulin for us. We rely on Woodstock Sterile Solutions to serve as an additional manufacturer of Nebulized Tyvaso drug product. We currently rely entirely on MannKind to manufacture Tyvaso DPI finished drug product and inhalers. We have initiated efforts to qualify a contract manufacturer as a second manufacturing source for dinutuximab, the active ingredient in Unituxin. We have no plans to develop a redundant manufacturing source for finished Tyvaso DPI, Orenitram, or Unituxin drug product, or Tyvaso DPI inhalers.

We rely on Forj Medical 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. We are in the process of qualifying our RTP facility to produce our primary commercial supply of ralinepag, if and when it is approved by the FDA.

We rely entirely on third parties to supply pumps and other supplies necessary to administer Remodulin. ICU Medical discontinued manufacturing the MS-3 system used to administer subcutaneous Remodulin, and specialty pharmacy distributors informed us that supplies of MS-3 pumps are exhausted, although a limited number of refurbished pumps may be available for use with generic treprostinil. ICU Medical has also discontinued manufacturing and distribution of the CADD-Legacy system used to administer intravenous 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 for us. 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. There are additional ancillary supplies used with these pumps, and there are a limited number of manufacturers that supply them.

Although we believe that additional third parties could provide similar products, services, and materials, there are few companies that could replace our existing third-party manufacturers and suppliers. A change in supplier or manufacturer could cause a delay in the manufacturing, distribution, and research efforts associated with our respective products or result in increased costs. See also Item 1A—Risk Factors included in this Report.

Competition

Many drug companies engage in research, development, and commercialization of products to treat cardiopulmonary diseases, pulmonary diseases, and cancer. For the treatment of PAH, we compete with many approved products in the United States and the rest of the world. In the U.S., these competitive therapies include oral ERAs (Letairis® (ambrisentan), Opsumit® (macitentan), Tracleer® (bosentan), generic bosentan, and generic ambrisentan); prostacyclin-class therapies Uptravi® (oral selexipag), Veletri® (intravenous epoprostenol), Ventavis® (inhaled iloprost), Yutrepia® (treprostinil inhalation powder), generic intravenous epoprostenol, and generic treprostinil injection; PDE-5 inhibitors (Revatio® (sildenafil), generic sildenafil, and generic tadalafil); an SGC stimulator Adempas® (riociguat); an activin pathway inhibitor Winrevair (sotatercept-csrk) delivered via subcutaneous injection; and an oral combination product known as Opsynvi®, comprised of tadalafil and macitentan. Some of these therapies are manufactured and marketed by large pharmaceutical companies such as Johnson & Johnson, Gilead Sciences, Inc., Bayer Schering Pharma AG, GSK plc, and Merck, as well as a variety of large generic drug manufacturers. In the fourth quarter of 2025, the manufacturer of Flolan® (intravenous epoprostenol) discontinued manufacture of the product.

Merck’s Winrevair was approved by the FDA to treat PAH in March 2024. A majority of patients enrolled in the STELLAR pivotal clinical trial of Winrevair were on background prostacyclin-class therapies such as treprostinil, and to date we have not seen a material impact on the use of our treprostinil-based therapies. However, some physicians may choose to prescribe Winrevair prior to initiating prostacyclin therapy, which could negatively impact our revenues, and Merck has completed clinical studies that could result in an earlier use of Winrevair for treating PAH.

In May 2025, Liquidia received final FDA approval to market Yutrepia, a dry powder formulation of treprostinil, to treat PAH and PH-ILD. Yutrepia competes directly with our treprostinil-based products, including in particular Nebulized Tyvaso and Tyvaso DPI. We have litigation pending which could, if successful, result in the removal of PH-ILD as a labeled indication for Yutrepia. See Note 14—Litigation, to our consolidated financial statements included in this Report, for additional details.

Nebulized Tyvaso, Tyvaso DPI, and Yutrepia are currently the only FDA-approved inhaled prostacyclin analogues available in the United States for newly diagnosed patients.

There are a wide variety of investigational PAH therapies in development. Therapies in registration-phase studies, or which have completed registration-phase studies, include the following:

•L606, an inhaled, liposomal form of treprostinil currently being developed by Pharmosa Biopharm Inc. (Pharmosa) and Liquidia for treatment of PAH and PH-ILD, intended to be dosed twice daily. 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. On October 2, 2024, Liquidia and Pharmosa announced that they amended the licensing agreement to expand Liquidia’s licensed territory to include Europe, Japan, and elsewhere, and to include rights to Pharmosa’s nebulizers for use with L606.

•Seralutinib (GB002), a small molecule tyrosine kinase inhibitor being developed by Gossamer Bio, Inc. (Gossamer) as a dry powder inhaled product for PAH and PH-ILD. In February 2026, Gossamer announced that a phase 3 study in PAH failed to meet its primary endpoint with statistical significance, but that the company will continue its efforts to seek approval for PAH. In addition, Gossamer initiated a phase 3 study in PH-ILD during the fourth quarter of 2025.

•TPIP (INS1009), an inhaled dry powder formulation of treprostinil palmitil intended to be dosed once per day, being developed by Insmed Incorporated. In January 2026, the Office of Orphan Products Development of the FDA granted orphan drug designation to TPIP for the treatment of patients with PAH on the basis of plausible clinical superiority to approved versions of treprostinil. The company has indicated that they plan to initiate a phase 3 study of TPIP in PAH

patients in the first half of 2026. In addition, the company initiated a phase 3 study in PH-ILD in the fourth quarter of 2025, and disclosed that they plan to initiate additional phase 3 studies in PPF and IPF in the second half of 2026.

Additional therapies being studied for PAH include the following, among others: Cereno Scientific AB’s valproic acid (CS1) (phase 2b planned for 2026); Boston Scientific’s TIVUS™ (pivotal trial); Respira Therapeutics’ vardenafil (RT234) (phase 2b); Chugai Pharmaceutical Co., Ltd’s satralizumab (phase 2); Regeneron’s REGN13335 (phase 2); Apollo Therapeutics, APL-9796 (phase 2); Pfizer’s PF-07868489 (phase 1/2); and Tiakis Biotech’s tiprelestat (phase 2). In addition, Infusyn Therapeutics has indicated it is developing an implantable pump to deliver intravenous iloprost for PAH.

Oral non-prostacyclin therapies (such as PDE-5 inhibitors and ERAs) are commonly prescribed as first-line treatments for less severely ill PAH patients. As patients progress in their disease severity, additional advanced approved therapies, such as inhaled prostacyclin analogues (including Tyvaso DPI and Nebulized Tyvaso) or infused prostacyclin analogues (including Remodulin) are then commonly added. Orenitram was the first approved oral prostacyclin-class therapy for PAH in the United States, and offers a more convenient alternative therapy to Remodulin and Nebulized Tyvaso. The use of available oral therapies could delay many patients’ need for inhaled or infused prostacyclin therapy. As a result, the availability of oral therapies affects demand for our inhaled and infused products.

Orenitram faces direct competition from Uptravi, which is indicated to delay disease progression and reduce the risk of hospitalization for PAH, and will compete with a generic version of Uptravi which is expected to launch in 2026. Orenitram’s initial indication was limited to the improvement of exercise capacity, which may have led physicians to prescribe Uptravi instead of Orenitram. However, Uptravi is an oral IP prostacyclin receptor agonist. While prostacyclin analogues such as Orenitram broadly mimic the effect of prostacyclin, IP prostacyclin receptor agonists bind selectively to the IP receptor, one of several prostacyclin receptors. Given the progressive nature of PAH, many patients initiate Orenitram or another one of our treprostinil-based therapies after their disease progresses while taking Uptravi. In August 2018, we announced the results of our FREEDOM-EV clinical study, which demonstrated that Orenitram delays time to clinical worsening, demonstrated improvement across key clinical measures, and, at study closure, indicated a positive impact on survival rates. In October 2019, the FDA approved a supplement to our Orenitram NDA expanding the Orenitram label to indicate that it also delays disease progression, in addition to improving exercise capacity. We believe that these clinical results and updated labeling have resulted in increased use of Orenitram. We are developing a next-generation IP receptor agonist called ralinepag, for PAH. If approved by the FDA, we believe ralinepag will have a competitive advantage against Uptravi (and generic selexipag, if launched) due to its once-daily dosing profile, whereas Uptravi is dosed twice daily.

We have faced generic competition for Adcirca since the launch of generic tadalafil in the United States in August 2018, which has significantly reduced our Adcirca revenues. We have also faced generic competition for Remodulin in the United States and certain European countries since 2019. Finally, we have entered into settlement agreements with Actavis and ANI permitting them to launch generic versions of Orenitram in the United States in June 2027 and December 2027, respectively, or earlier under certain circumstances. We have also entered into a settlement agreement with Watson permitting it to launch a generic version of Nebulized Tyvaso in the United States as early as January 2026, although to date Watson has not received FDA approval to do so. For details regarding these and other potential generic competitors, see the section above entitled Patents and Other Proprietary Rights, Strategic Licenses, and Market Exclusivity—Generic Competition and Challenges to our Intellectual Property Rights.

Aside from Tyvaso DPI, Nebulized Tyvaso, and Yutrepia, there are currently no approved therapies indicated to treat PH-ILD. Several PAH drug candidates are also being developed for PH-ILD (e.g., L606, seralutinib, TPIP, and Cereno Scientific AB’s CS014). In addition, Foresee Pharmaceuticals is developing mirivadelgat for PH-ILD (phase 2), and Pulmovant is developing mosliciguat for PH-ILD (phase 2). Other companies are now developing, or may in the future develop, other therapies to treat PH-ILD. In addition, the use of antifibrotic therapies to treat underlying lung disease (such as the IPF therapies discussed below) could delay the onset of group 3 pulmonary hypertension.

If the TETON program(s) are successful, we anticipate seeking IPF and PPF indications for Nebulized Tyvaso. There are currently only three branded therapies that are approved by the FDA to treat IPF: Ofev® (nintedanib) and Jascayd® (nerandolimast), which are marketed by Boehringer Ingelheim International GmbH, and Esbriet® (pirfenidone), which is marketed by F. Hoffman-La Roche Ltd. (Roche). Ofev and Jascayd are also approved to treat PPF. A generic version of Esbriet is also available to treat IPF. There are potentially competing therapies in advanced clinical development for IPF. These therapies include, but are not limited to: Bristol Myers Squibb Company’s admilparant (BMS-986278) (phase 3); Avalyn Pharma’s AP01 (inhaled pirfenidone) (phase 2b) and AP02 (inhaled nintedanib) (planning phase 2); Calliditas Therapeutics’ setanaxib (phase 2); Cumberland Pharmaceuticals’ Vasculan® (ifetroban) (phase 2); Daewoong Pharmaceutical’s bersiporocin (DWN12088) (phase 2); Endeavor Biosciences’ taladegib (NV-101) (phase 2a); Roche/Genentech’s vixarelimab (phase 2); GSK’s GSK3915393 (phase 2); Insilico Medicine’s ISM001_055 (phase 2); PureTech Health’s deupirfenidone (LYT-100) (phase 3 ready); Redx Pharma’s zelasudil (phase 2); Syndax Pharmaceuticals’ Niktimvo® (axatilimab-csfr) (phase 2); Calluna Pharma (Cal101) (phase 2); GRI Bio’s GRI-0621 (phase 2); Amgen’s Tezepelumab-ekko (phase 2); Lilly’s MTX-463 (phase 2); and Vicore Pharma’s buloxibutid (phase 2). Some or all of these therapies may also be developed as treatments for PPF. As noted above, Insmed has also announced plans to study TPIP for IPF and PPF.

Unituxin may face competition from Qarziba® (dinutuximab beta), an antibody product developed by Apeiron Biologics AG that is approved in Europe to treat high-risk neuroblastoma but is not approved in the United States. In October 2016, EUSA Pharma (UK) Ltd. (which was acquired by Recordati Group in 2022) announced it had acquired global commercialization rights to Qarziba. In addition, Y-mAbs Therapeutics, Inc. (Y-mAbs), is developing several GD-2 targeting drug candidates, and

in November 2020 obtained FDA approval for Danyelza® (naxitamab-gqgk) to treat pediatric and adult patients with relapsed and refractory (second line) high-risk neuroblastoma in bone or bone marrow. Y-mAbs launched commercial sales of Danyelza in 2021. Y-mAbs is also conducting studies of naxitamab for frontline high-risk neuroblastoma.

We compete with the developers, manufacturers, and distributors of all of the products noted above for customers, funding, access to licenses, personnel, third-party collaborators, product development, and commercialization. Some of these companies have substantially greater financial, marketing, sales, distribution and technical resources, and more experience in research and development, product development, manufacturing and marketing, clinical trials, and regulatory matters, than we have.

Governmental Regulation

Pharmaceutical Product Approval Process

The research, development, testing, manufacture, promotion, marketing, distribution, sampling, storage, approval, labeling, record keeping, post-approval monitoring and reporting, and import and export of pharmaceutical products are extensively regulated by governmental agencies in the United States and in other countries. In the United States, failure to comply with requirements under the Federal Food, Drug, and Cosmetic Act (FDC Act), the Public Health Service Act (PHSA), and other federal statutes and regulations, may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to approve pending NDAs or BLAs, warning letters, product recalls, product seizures, total or partial suspension of manufacturing or distribution, injunctions, fines, civil penalties, and criminal prosecution.

Satisfaction of FDA pre-market approval requirements is extremely costly and typically takes many years. The actual cost and time required may vary substantially based upon the type, complexity, and novelty of the product or disease. Drugs are subject to rigorous regulation and requirements by the FDA in the United States, the EMA in the European Union (EU), and similar regulatory authorities in other countries. The steps ordinarily required before a new drug may be marketed in the United States, which are similar to steps required in most other countries, include: (1) preclinical testing; (2) submission to the FDA of an IND; (3) clinical studies, including well-controlled clinical trials, in healthy volunteers and patients to establish safety, efficacy, and dose-response characteristics for each drug indication; (4) submission of an NDA or BLA to the FDA; and (5) FDA acceptance, review, and approval of the NDA or BLA.

Preclinical Testing

Preclinical tests include laboratory evaluation of product chemistry and formulation, as well as animal studies to explore toxicity and for proof-of-concept. The conduct of the preclinical tests must comply with federal regulations and requirements including good laboratory practices.

Submission of IND

The results of preclinical testing are submitted to the FDA as part of an IND, along with other information including information about product chemistry, manufacturing, and controls, and a proposed clinical trial protocol. Absent FDA objection within 30 days after submission of an IND, the IND becomes effective and the clinical trial proposed in the IND may begin.

Clinical Studies

Clinical trials involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of a qualified investigator. Clinical trials must be conducted: (1) in compliance with federal regulations; (2) in compliance with good clinical practices (GCP), an international standard meant to protect the rights and health of patients and to define the roles of clinical trial sponsors, administrators, and monitors; and (3) under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety and the criteria to be evaluated.

The FDA may order the temporary or permanent discontinuation of a clinical trial at any time or impose other sanctions if it believes that the clinical trial is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients. The study protocol and informed consent information for patients in clinical trials must also be approved by an institutional review board (IRB). An IRB may also require the clinical trial at a site to be halted temporarily or permanently for failure to comply with the IRB’s requirements, or may impose other conditions.

Clinical trials in support of an NDA typically are conducted in sequential phases, but the phases may overlap.

•Phase 1 involves the initial introduction of the drug into healthy human subjects or patients to assess metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses, and, if possible, early evidence on effectiveness.

•Phase 2 usually involves studies in a limited patient population to assess the efficacy of the drug in specific, targeted indications, explore tolerance and optimal dosage, and identify possible adverse effects and safety risks.

•Phase 3 trials, also called pivotal studies, major studies or advanced clinical trials, demonstrate clinical efficacy and safety in a larger number of patients, typically at geographically diverse clinical study sites, and permit the FDA to evaluate the overall benefit-risk relationship of the drug and provide adequate information for drug labeling.

•Phase 4 studies are often conducted following marketing approval, in order to meet regulatory requirements or to provide additional data related to drug use.

FDA Approval Process

After successful completion of the required clinical testing, an NDA is typically submitted to the FDA in the United States, and a marketing authorization application is typically submitted to the EMA in the EU. FDA approval of the NDA is required before the product may be marketed in the United States.

The FDA has 60 days from its receipt of an NDA to determine whether the application will be accepted for filing. If the FDA determines that the application is not sufficiently complete to permit substantive review, it may request additional information and decline to accept the application for filing until the information is provided. Once the submission is accepted for filing, the FDA begins an in-depth review. Most applications for non-priority drugs are reviewed within ten to twelve months. Special expedited pathways, including “accelerated approval,” “fast track” status, “breakthrough therapy” status, and “priority review” status, are granted for certain drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. These special pathways can significantly reduce the time it takes for the FDA to review an NDA, but do not guarantee that a product will receive FDA approval.

The FDA may refer applications for novel pharmaceutical products or pharmaceutical products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation, and a recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations. In addition, before approving an NDA, the FDA will typically inspect one or more clinical sites to assess compliance with GCP and the facility or the facilities at which the drug is manufactured to ensure they are in compliance with the FDA’s current Good Manufacturing Practices (cGMP).

After the FDA evaluates the NDA and the manufacturing facilities, the FDA may issue either an approval letter or a complete response letter, which generally outlines the deficiencies in the submission and may require substantial additional testing or information in order for the FDA to reconsider the application. If and when those conditions have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included. Even after a resubmission, the FDA may decide that the application does not satisfy the regulatory criteria for approval.

Post-Approval Regulatory Requirements

Once an NDA is approved, the product is subject to continuing regulation. For instance, pharmaceutical products may be marketed only for their approved indications and in accordance with the provisions of their approved labeling. The FDA closely regulates the post-approval marketing, labeling, and advertising of prescription drugs, including direct-to-consumer advertising, off-label promotion, industry-sponsored scientific and educational activities, and promotional activities involving the Internet.

Adverse event reporting and submission of periodic reports continue to be required following FDA approval of an NDA. In addition, as a condition of NDA approval, the FDA may require post-marketing testing, including phase 4 clinical studies, and/or a risk evaluation and mitigation strategy (REMS) to help ensure that the benefits of the drug outweigh the potential risks. Additionally, quality control as well as drug manufacture, packaging, and labeling procedures must continue to conform to cGMP requirements. Manufacturing facilities are subject to continual review and periodic inspections by the FDA and certain state agencies.

Regulatory authorities may withdraw product approvals or request product recalls if a company fails to comply with regulatory standards or if previously unrecognized problems are subsequently discovered. Discovery of previously unknown problems with a product, including adverse events or problems with manufacturing processes of unanticipated severity or frequency, or failure to comply with regulatory requirements, may also result in: (1) revisions to the approved labeling; (2) imposition of post-market studies or clinical trials to assess new safety risks; or (3) imposition of distribution or other restrictions under a REMS program. 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.

Approval of Changes to an Approved Product

Certain changes to the conditions established in an approved application, including changes in indications, labeling, equipment, or manufacturing processes or facilities, require submission and FDA approval of an NDA or NDA supplement before the change can be implemented. An NDA supplement for a new indication typically requires clinical data similar to

that in the original application, and the FDA uses the same procedures and actions in reviewing supplements as it does in reviewing NDAs.

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. The first NDA or BLA applicant to receive orphan drug designation and FDA approval for a particular active ingredient to treat a particular disease via a particular delivery method is entitled to a seven-year exclusive marketing period in the United States. During the seven-year period, the FDA may not approve any other application to market the same drug for the same disease, except in limited circumstances such as a showing of clinical superiority to the product with orphan drug exclusivity, meaning that it has greater effectiveness or safety, or provides a major contribution to patient care (such as a change in delivery system).

Patent Term and Regulatory Exclusivity

In 1984, the Hatch-Waxman Act created a faster approval process for generic drugs, called the ANDA. Generally, an ANDA provides for marketing of a drug product that has the same active ingredients in the same strength(s), route of administration, and dosage form as an approved drug and has been shown through bioequivalence testing to be therapeutically equivalent to the approved drug, which is known as the reference listed drug (RLD). ANDA applicants are not required to conduct or submit results of preclinical or clinical tests to prove the safety or effectiveness of their drug product, other than the requirement for bioequivalence testing. Drugs approved in this way are commonly referred to as “generic equivalents” to the approved drug, and can often be substituted by pharmacists under prescriptions written for the original approved drug.

NDA applicants are required to identify each patent with claims that cover the drug (drug substance or drug product) or FDA-approved method of using the drug. Upon product approval, these patents are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. Every ANDA applicant must make one of several certifications to the FDA with regard to each Orange Book listed patent for the RLD. A Paragraph III certification states that the ANDA applicant seeks approval after the patent expires. A Paragraph IV certification asserts that the patent does not block approval of the ANDA, either because the patent is invalid or unenforceable or because the patent, even if valid, is not infringed by the new product. If the applicant does not challenge the listed patents, the ANDA will not be approved until all the listed patents claiming the referenced product have expired. Alternatively, for a method of use patent covering an approved indication, an ANDA applicant may submit a statement to the FDA that the company is not seeking approval for the covered indication.

If the ANDA applicant has submitted a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months, expiration of the patent, settlement of the lawsuit, or a decision in the infringement case that is favorable to the ANDA applicant.

The Hatch-Waxman Act also provides that patent terms may be extended to compensate for some of the patent life that is lost during the FDA regulatory review period for a product.

An ANDA also will not be approved until any non-patent exclusivity, such as exclusivity for obtaining approval of an NDA for a new chemical entity, has expired. Federal law provides a period of five years following approval of a drug containing no previously approved active ingredient, during which ANDAs for generic versions of those drugs cannot be submitted unless the submission contains a Paragraph IV certification, in which case the submission may be made four years following the original product approval. Following approval of an application to market a drug that contains previously approved active ingredients in a new dosage form, route of administration or combination, or for a new condition of use that was required to be supported by new clinical trials conducted by or for the sponsor, the FDC Act provides three years of exclusivity during which the FDA cannot grant effective approval of an ANDA for such new condition of use, dosage form, or strength that meets certain statutory requirements.

Section 505(b)(2) New Drug Applications

Most drug products (other than biological products) obtain FDA marketing approval pursuant to an NDA submitted under Section 505(b)(1) of the FDC Act, or an ANDA. A third alternative is a special type of NDA submitted under Section 505(b)(2) of the FDC Act, commonly referred to as a Section 505(b)(2) NDA, which enables the applicant to rely, in part, on the FDA’s finding of safety and efficacy data for an existing product, or published literature, in support of its application.

Section 505(b)(2) permits the filing of an NDA in which the applicant relies, at least in part, on information from studies made to show whether a drug is safe or effective that were not conducted by or for the applicant and for which the applicant has not

obtained a right of reference or use. A Section 505(b)(2) applicant may eliminate the need to conduct certain preclinical or clinical studies, if it can establish that reliance on studies conducted for a previously-approved product is scientifically appropriate. The FDA may also require companies to perform additional studies or measurements to support the change from the approved product. The FDA may then approve the new product candidate for all or some of the labeled indications for which the referenced product has been approved, as well as for any new indication for which the Section 505(b)(2) NDA applicant has submitted data.

To the extent that the Section 505(b)(2) applicant relies on prior FDA findings of safety and efficacy, the applicant is required to certify to the FDA concerning any patents listed for the previously approved product in the Orange Book to the same extent that an ANDA applicant would. Thus, approval of a Section 505(b)(2) NDA can be delayed until all the listed patents claiming the referenced product have expired, until any non-patent exclusivity, such as exclusivity for obtaining approval of a new active ingredient, listed in the Orange Book for the referenced product has expired, and, in the case of a Paragraph IV certification and subsequent patent infringement suit, until the earlier of 30 months, settlement of the lawsuit or a decision in the infringement case that is favorable to the Section 505(b)(2) applicant.

Marketing Pharmaceutical Products Outside the United States

Outside of the United States, our ability to market our products is also contingent upon receiving marketing authorizations from regulatory authorities. The foreign regulatory approval process may include some or all of the risks associated with the FDA review and approval process set forth above, and the requirements governing the conduct of clinical trials and marketing authorization may vary widely from country to country. In most cases, our distribution partners are entirely responsible for obtaining marketing approvals outside the United States.

Biologics

Biological products used for the prevention, treatment, or cure of a disease, or condition, of a human being are subject to regulation under the FDC Act and the PHSA. Biological products are approved for marketing via a BLA that follows an application process and carries approval requirements that are very similar to those for NDAs. The PHSA also provides authority to the FDA to immediately suspend licenses in situations where there is a danger to public health, to prepare or procure products in the event of shortages and critical public health needs, and to authorize the creation and enforcement of regulations to prevent the introduction, or spread, of communicable diseases in the United States.

After a BLA is approved, the product may also be subject to official lot release, meaning the manufacturer must submit samples of each lot of product to the FDA together with a release protocol showing a summary of the history of manufacture of the lot and the results of all of the manufacturer’s tests performed on the lot. The FDA may also perform certain confirmatory tests on lots of some products, such as viral vaccines, before releasing the lots for distribution by the manufacturer. As with small-molecule drugs, after approval of biologics, manufacturers must address any safety issues that arise, are subject to recalls or a halt in manufacturing, and are subject to periodic inspection after approval.

The Biologics Price Competition and Innovation Act of 2009 created an abbreviated approval pathway for biological products shown to be “biosimilar” to an FDA-licensed reference biological product to minimize duplicative testing. Biosimilarity requires the absence of clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, which, absent a waiver, must be shown through analytical studies, animal studies, and at least one clinical study.

A reference biologic is granted 12 years of exclusivity from the time of first licensure of the reference product. The first biologic product submitted under the abbreviated approval pathway that is approved as a biosimilar and also meets additional standards for interchangeability with the reference product, has exclusivity against other biologics submitted under the abbreviated approval pathway for a set period. Because biologically sourced raw materials are subject to unique contamination risks, their use may be restricted in some countries.

Cell-Based and Tissue-Based Products

Manufacturers of cell- and tissue-based products must comply with the FDA’s current good tissue practices (cGTP), which are FDA regulations that govern the methods used in, and the facilities and controls used for, the manufacture of such products. The primary intent of the cGTP requirements is to ensure that cell- and tissue-based products are manufactured in a manner designed to prevent the introduction, transmission, and spread of communicable diseases. Cell and tissue-based products may also be subject to the same approval standards, including demonstration of safety and efficacy, as other biologic and drug products, if they meet certain criteria such as if the cells or tissues are more than minimally manipulated or if they are intended for a non-homologous use (a use different from the cell’s origin).

Regulation of Medical Devices

We currently do not hold any stand-alone medical device authorizations, but we do hold FDA authorization for the inhaler and nebulizer system as part of the drug-device combination NDAs for Tyvaso DPI and Nebulized Tyvaso, respectively. In addition, our business partners have the medical device clearances required to deliver our drugs, including, for example, the Remunity and RemunityPRO Pumps and the cartridge used with the MS-3 pump. Medical devices may also be subject to FDA approval and extensive regulation under the FDC Act. Medical devices are classified into one of three classes: Class I, Class II, or Class III. A higher class indicates a greater degree of risk associated with the device and a greater amount of control needed to ensure safety and effectiveness.

All devices, unless exempt by FDA regulation, must adhere to a set of general controls, including compliance with the applicable portions of the FDA’s Quality System Regulation (QSR), which sets forth good manufacturing practice requirements; facility registration and product listing; reporting adverse medical events; truthful and non-misleading labeling; and promotion of the device consistent with its cleared or approved intended uses. Class II and III devices are subject to additional special controls and may require FDA clearance of a premarket notification (510(k)) or approval of a premarket approval application (PMA).

Most Class I devices are exempt from FDA premarket review or approval. Class II devices, with some exceptions, must be “cleared” by the FDA through the 510(k) process, which requires a company to show that the device is “substantially equivalent” to certain “predicate” devices already on the market. To be substantially equivalent, the proposed device must have the same intended use as the predicate device, and either have the same technological characteristics as the predicate device or have different technological characteristics and not raise different questions of safety or effectiveness than the predicate device.

Devices deemed by the FDA to pose the greatest risks, such as life-sustaining, life-supporting, or some implantable devices, or devices that have a new intended use, or use advanced technology that is not substantially equivalent to that of a legally-marketed device, are placed in Class III, requiring approval of a PMA application. A PMA generally requires data from clinical trials that establish the safety and effectiveness of the device.

The FDA also allows the submission of a direct de novo petition. This procedure allows a manufacturer whose novel device is automatically classified into Class III to request down-classification of its medical device into Class I or Class II on the basis that the device presents low or moderate risk, rather than requiring the submission and approval of a PMA.

The 510(k), de novo, and PMA processes can be expensive, lengthy, and unpredictable. The FDA’s 510(k) clearance process usually takes from three to 12 months, but can last longer. The process of obtaining a PMA approval is much more costly and uncertain than the 510(k) clearance process and generally takes from one to three years, or even longer, from the time the application is filed with the FDA. In addition, a PMA approval generally requires the performance of one or more clinical trials. Despite the time, effort, and cost invested by a sponsor, a device may not be approved or cleared by the FDA.

Clinical trials for medical devices are subject to similar requirements as clinical trials with respect to drugs or biologics. Clinical trials involving significant risk devices (e.g., devices that present a potential for serious risk to the health, safety, or welfare of human subjects) are required to obtain both FDA approval of an investigational device exemption (IDE) application and IRB approval before study initiation. Clinical trials involving non-significant risk devices are not required to submit an IDE for FDA approval but must obtain IRB approval before study initiation. During a study, the sponsor is required to comply with the applicable FDA requirements, including, for example, trial monitoring, selecting clinical investigators and providing them with the investigational plan, ensuring IRB review, adverse event reporting, record keeping requirements, and prohibitions on the promotion of investigational devices or on making safety or effectiveness claims about them. The clinical investigators in the clinical study are also subject to FDA regulations and must obtain patient informed consent, rigorously follow the investigational plan and study protocol, control the disposition of the investigational device, and comply with all reporting and recordkeeping requirements. Additionally, after a trial begins, the sponsor, the FDA, or the IRB could suspend or terminate a clinical trial at any time for various reasons, including a belief that the risks to study subjects outweigh the anticipated benefits.

After a device is cleared or approved for marketing, numerous and pervasive regulatory requirements continue to apply. These include requirements pertaining to registration and device listing; QSR manufacturing requirements; labeling regulations and promotional restrictions; and reporting of device malfunctions and death and serious injuries that may have been caused by the device. The FDA has authority to order product recalls and to require post-market surveillance. In addition, certain product modifications to 510(k)-cleared and PMA-approved devices require further clearance and approval.

The FDA has broad regulatory and enforcement powers with respect to medical devices, similar to those for drugs and biologics. The FDA enforces these regulatory requirements through, among other means, periodic unannounced inspections. The Food and Drug Omnibus Reform Act gives the FDA authority to request medical device facility records in advance of, or in lieu of, inspections. Any failure to comply with applicable regulatory requirements could result in enforcement action by the FDA, which may include sanctions such as:

•adverse publicity, warning letters, untitled letters, it has come to our attention letters, fines, injunctions, consent decrees, and civil penalties;

•repair, replacement, refunds, recall, or seizure of products;

•operating restrictions, partial suspension, or total shutdown of production;

•denial of requests for regulatory clearance or PMA approval of new products or services, new intended uses, or modifications to existing products or services;

•withdrawal of regulatory clearance or PMA approvals that have already been granted; or

•criminal prosecution.

The FDA also administers certain controls over the import and export of medical devices to and from the United States. Additionally, each foreign country subjects medical devices to its own regulatory requirements. Medical devices are CE marked and placed on the market in the EU at the discretion and on the liability of their manufacturer following a conformity assessment process that may include the participation of a notified body. States also impose regulatory requirements on medical device manufacturers and distributors. 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.

Combination Products

A combination product is a product that combines two or more FDA-regulated product components or products, e.g., a drug-device or a device-biologic. A combination product can take a variety of forms, such as a single item made by physically or chemically combining components, or a single unit made of separately packaged products. Each combination product is assigned a lead FDA center, which has jurisdiction for the premarket review and regulation of the product, based on which constituent part of the combination product provides the primary mode of action, i.e., the mode of action expected to make the greatest contribution to the overall intended therapeutic effect of the product. Depending on the type of combination product, the FDA may require a single application for approval, clearance, or licensure of the combination product, or separate applications for the constituent parts. During the review of marketing applications, the lead FDA center may consult or collaborate with other FDA centers.

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. 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. In 2020, the FDA approved our new animal drug application (NADA) for the genetic modification to the GalSafe lineage of pigs that are intended for use as a source of human food consumption and as a source for potential therapeutic products. The GalSafe pig is the source of our development-stage UThymoKidney product. 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 designated pathogens.

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 anticipate that Miromatrix products will each be regulated as a combination product consisting of a device (a porcine-derived extracellular matrix) and a biologic (the human cells used to cellularize the extracellular matrix). We expect that CBER will have primary jurisdiction as the lead FDA review center for Miromatrix products because human cells provide the fundamental mode of action in these products, and that each product will require a BLA. 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.

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.

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.

Government Reimbursement of Pharmaceutical Products

In the United States, many independent third-party health plans, and government health care programs, such as Medicaid and Medicare, pay for patient use of our commercial products. A material portion of our product sales are reimbursed under

these government programs. The availability of adequate government reimbursement for our products is subject to regulatory changes and controls affecting these programs.

Medicaid is a joint federal and state program that benefits low‑income and disabled individuals. It is administered by the states and CMS, the federal agency that also administers the Medicare program. We participate in the Medicaid Drug Rebate Program, pursuant to which, as a condition of having federal funds made available for our drugs under Medicaid and Medicare Part B, we are required to pay a rebate to each state Medicaid program for each unit of our covered outpatient drugs dispensed to Medicaid beneficiaries and reimbursed by a state Medicaid program. Medicaid rebates are based on pricing data we report on a monthly and quarterly basis to CMS. If we become aware that our reporting for a prior quarter was incorrect, or has changed as a result of recalculation of the pricing data, we are obligated to resubmit the corrected data to CMS for up to three years after those data originally were due.

Medicare is a federal program that is administered by CMS that provides covered health care benefits to individuals aged 65 or over and to certain disabled and chronically ill persons. Specifically, Medicare Part A covers inpatient hospital benefits, Medicare Part B covers physician-administered drugs (as well as physician services and outpatient care), and Medicare Part D covers self-administered drugs. We are required to provide average sales price information on a quarterly basis to CMS for our products that are payable under Medicare Part B.

Our drugs are covered under Medicaid and Medicare as follows:

•Tyvaso DPI, Orenitram, and Adcirca are reimbursed under Medicare Part D, and we pay rebates to Part D plans that cover these products.

•Remodulin and Nebulized Tyvaso are reimbursable under Medicare Part B. The Medicare Part B contractors who administer the program cover Remodulin and Nebulized Tyvaso under local coverage determinations and provide reimbursement according to statutory guidelines.

•Medicaid also covers Remodulin, Tyvaso DPI, Nebulized Tyvaso, Adcirca, Orenitram, and Unituxin, and, as noted above, we must pay Medicaid rebates on this utilization.

•Unituxin is administered entirely as an in-patient therapy and would typically be reimbursed under Medicare Part A. However, because Unituxin is indicated for the treatment of a pediatric cancer, Medicare is unlikely to cover treatment, but Medicaid may cover pediatric patients requiring care.

As discussed under the risk factor entitled, Government healthcare reform and other reforms could adversely affect our revenue, costs, and results of operations, the Inflation Reduction Act (IRA) enacted in 2022, regulations proposed by the Trump administration (referred to as GLOBE and GUARD), and other federal measures, if finalized or enacted, will likely have significant impacts on prices and reimbursement rates, particularly in Medicare. Individual U.S. states have also enacted, or are considering enacting, legislation to limit the growth of healthcare costs, including the cost of prescription drugs. We continue to evaluate the possible impacts on our commercial and pipeline products.

Federal law requires that any company that 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. The 340B program, which is administered by the Health Resources and Services Administration (HRSA), requires participating manufacturers to agree to charge statutorily defined covered entities no more than the 340B “ceiling price” for the manufacturer’s covered outpatient drugs. These 340B covered entities include a variety of community health clinics and other entities that receive health services grants from the Public Health Service, as well as hospitals that serve a disproportionate share of low-income patients.

In order to be eligible to have our products paid for with federal funds under Medicaid and Medicare Part B and purchased by certain federal agencies and grantees, we also participate in the U.S. Department of Veterans Affairs (VA) Federal Supply Schedule (FSS) pricing program. Under this program, we are obligated to make our products available for procurement under an FSS contract under which we must comply with standard government terms and conditions and charge a price to certain federal agencies that is no higher than the statutory federal ceiling price. We also participate in the Tricare Retail Pharmacy program, under which we pay quarterly rebates on utilization of innovator products that are dispensed through the Tricare Retail Pharmacy network to Tricare beneficiaries.

Anti-Kickback, False Claims Laws, and The Prescription Drug Marketing Act

The federal Anti-Kickback Statute (AKS) prohibits, among other things, knowingly and willfully offering, paying, soliciting, or receiving remuneration to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of, or referring an individual for the furnishing of, any healthcare item or service reimbursable under Medicare, Medicaid, or other federally financed healthcare programs.

The False Claims Act (FCA) prohibits any person from, among other things, presenting, or causing to be presented, a false or fraudulent claim for payment of government funds, or making, or causing to be made, a false statement material to a false or fraudulent claim. Many states also have statutes or regulations similar to the AKS and the FCA, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payer.

The federal Physician Payments Sunshine Act, implemented as the Open Payments Program, requires certain manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program (with certain exceptions) to report annually to CMS information related to payments and other transfers of value to various healthcare professionals, including physicians, physician assistants, nurse practitioners, and clinical nurse specialists, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.

We are also subject to numerous other anti-bribery and anti-fraud laws, including the U.S. Foreign Corrupt Practices Act, the UK Bribery Act, and the federal Civil Monetary Penalties Law.

Sanctions under these federal and state laws may include treble damages, civil penalties, exclusion of a manufacturer’s products from reimbursement under government programs, criminal fines, and imprisonment.

Outside the U.S., interactions between pharmaceutical companies and physicians are also governed by strict laws, regulations, industry self-regulation codes of conduct, and physicians’ codes of professional conduct. 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. Certain EU member states, or industry codes of conduct, require that payments made to physicians be publicly disclosed. Moreover, agreements with physicians must often be the subject of prior notification and approval by the physician’s employer, his/her competent professional organization, and/or the competent authorities of the individual EU member states. Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines, or imprisonment.

State Pharmaceutical and Medical Device Marketing Laws

Several jurisdictions require pharmaceutical companies to report expenses related to the marketing and promotion of pharmaceutical products and to report gifts and payments to healthcare practitioners in those jurisdictions, or to obtain licenses for sales representatives and require them to satisfy educational and other requirements. Some of these jurisdictions also prohibit various marketing related activities. Still other states require the disclosure of information related to drug pricing and clinical studies and their outcomes. In addition, certain states require pharmaceutical companies to implement compliance programs or marketing codes and several other states are considering similar proposals. Compliance with these laws is difficult and time consuming, and companies that do not comply with these state laws face civil penalties or other civil enforcement action.

Privacy Laws

We must comply with numerous federal, state, and non-U.S. laws that govern the privacy and security of health and other personal information. In the U.S., numerous federal and state laws and regulations govern the collection, use, disclosure, and protection of health related and other personal information. Many of these laws differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts. Compliance with these laws is difficult, constantly evolving, and time consuming. Federal regulators, state attorneys general, and plaintiffs’ attorneys, including class action attorneys, have been and will likely continue to be active in this space.

The Health Insurance Portability and Accountability Act of 1996 (HIPAA) imposes privacy, security, and breach reporting obligations, including mandatory contractual terms, with respect to safeguarding the privacy and security of individually-identifiable health information upon covered entities subject to the rule. We could be subject to criminal penalties if we knowingly obtain, use, or disclose individually-identifiable health information maintained by a HIPAA covered entity in a manner that is not authorized or permitted by HIPAA.

In addition, we are required to comply with the California Consumer Privacy Act (CCPA). The CCPA became effective in 2020 and establishes certain requirements for data use and sharing transparency, and provides California residents certain rights concerning the use, disclosure, and retention of their personal data. The obligations to comply with the CCPA and evolving legislation require us, among other things, to update our notices and develop new processes internally and with our partners. We may be subject to fines, penalties, or private actions in the event of non-compliance with these laws.

Outside the U.S., the legislative and regulatory landscape for privacy and data security continues to evolve. There has been increased attention to privacy and data security issues that could potentially affect our business, including the EU General Data Protection Regulation (GDPR), which became effective in 2018 and imposes potential penalties up to the greater of €20 million or four percent of annual global revenue for failure to comply with its requirements. In addition, the CCPA and laws and regulations enacted in the United States, Europe, Asia, and Latin America, increase potential enforcement and litigation activity.

Because we enroll EU subjects in certain of our clinical trials, we are subject to additional privacy restrictions, including restrictions relating to the collection, use, storage, transfer, and other processing of personal data, including personal health data, regarding individuals in the European Economic Area (EEA) as governed by the GDPR. The GDPR imposes several

requirements on companies that process personal data, strict rules on the transfer of personal data out of the EEA, including to the U.S., and fines and penalties for failure to comply with the requirements of the GDPR and the related national data protection laws of the EU member states. The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR. Compliance with the GDPR will be a rigorous and time-intensive process that may increase our cost of doing business or require us to change our business practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with any European activities.

Other Laws and Regulations

Numerous other statutory and regulatory regimes affect our business and operations. For example, our research and development efforts may be subject to laws, regulations, and recommendations related to safe working conditions, laboratory practices, use of animals in research and development activities, and the purchase, storage, movement, import, export, and use and disposal of hazardous or potentially hazardous substances. Antitrust and competition laws may restrict our ability to enter into certain agreements involving exclusive license rights. Future legislation and administrative action will continue to affect our business, the extent and degree of which we cannot accurately predict.

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. Our compliance with these requirements did not change during the past year, and is not expected to have a material effect upon our capital expenditures, cash flows, earnings, or competitive position.

Human Capital

We are united by our commitment to developing innovative therapies for unmet needs and our dedication to be responsible citizens that have a positive impact on patients, the environment, and society. Our employees, whom we call Unitherians, are mission critical to these commitments because they share the same passion and dedication to meeting our purpose. As of December 31, 2025, we had approximately 1,400 employees working across our 15 locations worldwide. None of our employees are covered by a collective bargaining agreement and we believe our overall relations with our employees are good.

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 2025, we achieved approximately $2.25 million in revenue per employee, which ranks near the top of our industry peer group. We believe this level of productivity is driven by a sustained focus on our people and our commitment to fostering engagement, motivation, and alignment with our strategic 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 “Unitherian” Culture. We are intentional in our effort to maintain our entrepreneurial culture. We believe this instills a greater sense of ownership, meaning, and commitment in Unitherians, motivating them to go above and beyond to achieve our ambitious goals. Moreover, we are confident that our culture provides us with a competitive advantage by enabling us to attract the best talent to drive innovation and excellence in pursuit of our key strategic objectives. United Therapeutics is proud to be an equal opportunity employer, and does not discriminate based on race, religion, national origin, gender, age, marital status, disability, pregnancy, sexual orientation, gender identity or expression, military and veteran status, or any other basis protected by applicable law. We have a policy that prohibits all forms of unlawful harassment and retaliation, and we 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 publicly traded company in our industry to do so. As a public benefit corporation, our Board is now obligated to balance the interests of its patient-focused public benefit purpose, the financial interests of shareholders, and the interests of other stakeholders who are materially impacted by our conduct, such as Unitherians. We believe that this conversion has helped further underscore our commitment to Unitherians, as well as our mission-driven public benefit purpose of creating a brighter future for patients.

Talent Acquisition, Retention, and Talent Development. We strive to hire and retain exceptionally talented people who are passionately committed to our goals and who will thrive in our unique culture. We provide Unitherians with a variety of personal and professional development opportunities for them to grow and thrive. We believe that our talent acquisition, talent management, and talent development efforts are key factors in our low turnover compared to our industry peer group, which historically has trended well below the industry average. In 2025, we continued that trend with our voluntary turnover at 3.5 percent, well below industry average of 10 percent (based on June 1, 2024 through June 1, 2025 data from Aon’s Turnover Study for the Life Sciences/Biotech/Pharma Sector, published December 2025).

Inclusion and Belonging. We are proud of our diverse, engaged workforce, and we firmly believe that being a great place to work means cultivating a workplace that drives innovation, performance, and results through diverse perspectives and a culture of inclusion, with a commitment to providing equal employment opportunity for all. At United Therapeutics, inclusion is one of our five core values, deeply integrated into our employee experience.

Employee Development and Engagement. We seek to foster employee development and engagement by cultivating a culture of continuous growth and learning. We provide meaningful professional development opportunities, including leadership training, and actively encourage employees to pursue ongoing education, certifications, and skill enhancement through a variety of programs, including our education assistance program which enables full-time employees to pursue external coursework aligned with both business and individual career goals. Our commitment to quality and integrity is reinforced through required training on our Code of Conduct and other key organizational content. Employee input is central to our culture. We actively seek and value employee feedback, encouraging open dialogue and the sharing of ideas and concerns so we can take informed action. We believe our regular town hall meetings – featuring executive and business updates as well as patient-focused sessions – create meaningful connections between employees, leadership, and the patient experience. We also provide an internal social digital platform to strengthen connections across teams and functions. The effectiveness of these efforts is reflected in a recent external engagement survey conducted by Great Place to Work, where 94 percent of respondents indicated that they consider United Therapeutics “a great place to work.” We have consistently maintained this high level of engagement, with 90 percent or more of respondents from 2018 to 2025 affirming their positive experience with our organization.

Health and Safety. We are committed to providing and maintaining a safe, healthy, and secure workplace for all Unitherians. We have an environmental health and safety program. We routinely provide training on workplace safety and security to all Unitherians.

A Holistic Approach to Total Rewards and Employee Wellness. Our success depends on an exceptionally talented workforce. Because Unitherians are central to achieving our strategic goals, we invest in robust people programs that reflect the high value we place on their financial, mental, and physical wellbeing. Our comprehensive total rewards offering includes a competitive base salary, short-term cash incentive compensation, stock awards, and an employee stock purchase plan – enabling all full-time employees to share directly in the company’s financial success. For example, all full-time domestic Unitherians are eligible to receive minimum annual compensation of $75,000, including salary and bonus. We offer market-leading benefit programs, including a 401(k) savings plan with a company match, as well as health and welfare benefits such as flexible spending accounts, generous paid time off, parental bonding leave, adoption and surrogacy assistance, employee assistance programs, flexible work arrangements, tuition assistance, and more. We seek to consider the needs of Unitherians at all life stages, offering benefits like elder care support, tutoring/college coaching, pet care, and pet wellness benefits. We offer competitive medical, dental, vision, and prescription coverage that is available to both part-time and full-time Unitherians. Our inspiring work environments include several employee-focused amenities, such as on-site cafeterias, childcare centers, and state-of-the-art fitness centers.

Board Oversight. Our Board, through its Compensation Committee, oversees our human capital management strategies, including our focus on inclusion and belonging; workplace environment and culture; and talent development and retention. These topics are reviewed and discussed regularly at meetings of both the Compensation Committee and of the full Board.

Corporate Website

Our Internet website address is https://www.unither.com. Our filings on Form 10-K, Form 10-Q, Form 3, Form 4, Form 5, Form 8-K, and any and all amendments thereto are available free of charge through this Internet website as soon as reasonably practicable after they are filed with or furnished to the Securities and Exchange Commission (SEC). They are also available through the SEC at http://www.sec.gov/edgar/searchedgar/companysearch.html.

INFORMATION ABOUT OUR EXECUTIVE OFFICERS

The following is a list, as of February 25, 2026, setting forth certain information regarding our executive officers. Each executive officer holds office until the first meeting of the Board of Directors after the annual meeting of shareholders, and until his or her successor is elected and qualified or until his or her earlier resignation or removal. Each executive officer’s employment will end pursuant to the terms of his or her employment contract.

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. Her pioneering book, Your Life or Mine: How Geoethics Can Resolve the Conflict Between Private and Public Interests in Xenotransplantation, anticipated the need for both global virus bio-surveillance and a greatly expanded supply of transplantable organs. Dr. Rothblatt has a Ph.D. in medical ethics from the University of London.

Michael Benkowitz joined United Therapeutics in 2011 as our Executive Vice President, Organizational Development, and was promoted to President and Chief Operating Officer in 2016. He is responsible for all of our sales, marketing, market access, patient relations, manufacturing, medical affairs, and corporate compliance activities, most company-wide administrative functions, including human resources and information technology, many of our business development efforts, and several of our key business alliances and partnerships.

James C. Edgemond joined United Therapeutics in January 2013 as Treasurer and Vice President, Strategic Financial Planning. Mr. Edgemond was promoted to Chief Financial Officer and Treasurer in March 2015. Prior to joining United Therapeutics, he was Vice President, Corporate Controller, and Treasurer of Clark Construction Group from 2008 through January 2013. He also served in a variety of roles at The Corporate Executive Board Company from 1998 to 2008, serving as Executive Director, Finance from 2005 to 2008. He began his career as a public accountant at KPMG Peat Marwick LLP, from 1990 through 1998, where he served in a variety of roles, including as a Senior Manager prior to his departure.

Paul A. Mahon, J.D., has served as General Counsel and Corporate Secretary of United Therapeutics since its inception in 1996. In 2001, Mr. Mahon joined United Therapeutics full-time as Senior Vice President, General Counsel, and Corporate Secretary. In 2003, Mr. Mahon was promoted to Executive Vice President, General Counsel, and Corporate Secretary. Prior to 2001, he served United Therapeutics, beginning with its formation in 1996, in his capacity as principal and managing partner of a law firm specializing in technology and media law.