SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, announced today that the first patient has enrolled in the registration-phase TETON PPF study, which will evaluate nebulized Tyvaso® (treprostinil) Inhalation Solution in 698 adult patients with progressive pulmonary fibrosis (PPF).

SILVER SPRING，Md。＆RESEARCH TRIANGLE PARK，N.C.-（BUSINESS WIRE）-公益性公司United Therapeutics Corporation（纳斯达克股票代码：UTHR）今天宣布，第一名患者参加了注册阶段TETON PPF研究，该研究将评估698名成人进行性肺纤维化（PPF）患者的雾化Tyvaso®（曲前列环素）吸入溶液。

This is in addition to two separate ongoing registration-phase studies, TETON 1 and TETON 2, of nebulized Tyvaso in patients with another type of pulmonary fibrosis (PF) known as idiopathic pulmonary fibrosis (IPF)..

这是另外两项正在进行的注册阶段研究，TETON 1和TETON 2，用于雾化Tyvaso治疗另一种称为特发性肺纤维化（IPF）的肺纤维化（PF）患者。。

The 52-week study will evaluate the impact of nebulized Tyvaso on a key prognostic indicator for PPF known as forced vital capacity (FVC). PPF is a progressive form of interstitial lung disease (ILD) characterized by the loss of the ability of the lungs to transfer oxygen into the blood, ultimately resulting in respiratory failure and death..

为期52周的研究将评估雾化Tyvaso对PPF关键预后指标（称为用力肺活量（FVC））的影响。PPF是间质性肺疾病（ILD）的一种进行性形式，其特征是肺将氧气转移到血液中的能力丧失，最终导致呼吸衰竭和死亡。。

Nebulized Tyvaso is currently approved by the U.S. Food and Drug Administration (FDA) to treat both pulmonary arterial hypertension and pulmonary hypertension (PH) associated with interstitial lung disease (PH-ILD). The PH-ILD indication, which includes patients with PH associated with IPF and PPF, was added to the nebulized Tyvaso label in March 2021 based on the successful results of the INCREASE study.

雾化Tyvaso目前被美国食品和药物管理局（FDA）批准用于治疗与间质性肺病（PH-ILD）相关的肺动脉高压和肺动脉高压（PH）。根据INDUCE研究的成功结果，PH-ILD适应症（包括与IPF和PPF相关的PH患者）于2021年3月被添加到雾化Tyvaso标签中。

Nebulized Tyvaso is only approved for use for PPF patients who may also have documented PH, to improve exercise capacity. The TETON PPF study seeks to evaluate the use of nebulized Tyvaso in PPF patients irrespective of whether or not they have PH..

雾化Tyvaso仅被批准用于可能也记录了PH的PPF患者，以提高运动能力。TETON PPF研究旨在评估雾化Tyvaso在PPF患者中的应用，无论他们是否患有PH。。

“The progressive pulmonary fibrosis phenotype represents a group of ILD patients who only have limited treatment options currently available to them,” said Steven Nathan, M.D., Medical Director of the Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital in Falls Church, Virginia, who is also chair of the TETON program steering committee.

弗吉尼亚州福尔斯彻奇市Inova Fairfax医院晚期肺病和肺移植项目医学主任Steven Nathan博士说：“进行性肺纤维化表型代表了一组ILD患者，他们目前只有有限的治疗选择。”他也是TETON项目指导委员会主席。

“The broader ILD data set from the INCREASE study showed improvements in FVC beyond just IPF patients, and the data provide the foundation for further study of inhaled treprostinil’s anti-fibrotic and disease modifying mechanism of action in patients with other forms of fibrotic lung disease like PPF.”.

“来自增加研究的更广泛的ILD数据集显示FVC的改善不仅仅是IPF患者，并且这些数据为进一步研究吸入曲前列环素在其他形式的纤维化肺病患者中的抗纤维化和疾病改善作用机制奠定了基础像PPF“。

“The initiation of the global TETON PPF study illustrates confidence in nebulized Tyvaso as a potential treatment option for patients with fibrotic lung disease,” said Natalie Breytenbach, Pharm.D., Associate Director, Global Product Development at United Therapeutics and the company’s lead for the TETON PPF study.

联合治疗公司全球产品开发副主任Natalie Breytenbach博士说：“全球TETON PPF研究的启动说明了雾化Tyvaso作为纤维化肺病患者潜在治疗选择的信心。”TETON PPF研究。

“The expansion of TETON into the PPF patient population allows us to continue to evaluate inhaled treprostinil’s potential for treating this vulnerable group of patients in a robust global pivotal study.”.

“TETON扩展到PPF患者群体使我们能够继续评估吸入曲前列环素治疗这一弱势患者群体的潜力，这是一项强有力的全球关键性研究。”。

The TETON program in IPF and PPF was prompted by data from the INCREASE study of nebulized Tyvaso for the treatment of PH-ILD, which demonstrated improvements in certain key parameters of lung function in pulmonary hypertension patients with fibrotic lung disease (improved absolute FVC and reduced exacerbations of underlying lung disease).

IPF和PPF中的TETON计划是由雾化Tyvaso治疗PH-ILD的增加研究数据推动的，该研究证实了肺纤维化肺病肺动脉高压患者肺功能某些关键参数的改善（改善的绝对FVC和减少潜在肺部疾病的恶化）。

Specifically, in the INCREASE study, 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%; p=0.0380 and week 16: 3.5%; p=0.0147). In May 2022, data from the INCREASE open-label, long-term extension trial were presented at a medical conference, indicating that improvements in FVC were sustained for at least 64 weeks for PH-ILD patients with underlying IPF.

具体而言，在INCURE研究中，使用雾化Tyvaso治疗导致在第8周和第16周预测的FVC百分比显着改善，具有IPF潜在病因的受试者显示出最大改善（第8周：2.5%；p=0.0380和第16周：3.5%；p=0.0147）。2022年5月，来自增加开放标签的数据，在医学会议上提出了长期延长试验，表明对于具有潜在IPF的PH-ILD患者，FVC的改善持续至少64周。

For those patients who received placebo during the INCREASE study, marked improvements in FVC were observed following transition to nebulized Tyvaso during the open-label extension study. These data points, combined with substantial preclinical evidence of antifibrotic activity of treprostinil, suggest that nebulized Tyvaso may offer a treatment option for patients with IPF and PPF..

对于在增加研究期间接受安慰剂的那些患者，在开放标签延伸研究期间转变为雾化Tyvaso后观察到FVC的显着改善。这些数据点与曲前列环素抗纤维化活性的大量临床前证据相结合，表明雾化Tyvaso可能为IPF和PPF患者提供治疗选择。。

Tyvaso DPI® (treprostinil) Inhalation Powder is not being evaluated in the TETON program, but United Therapeutics intends to seek FDA approval to expand the Tyvaso DPI label to include IPF and PPF, following completion of the TETON studies and any FDA-required bridging studies.

Tyvaso-DPI®（曲前列环素）吸入粉末未在TETON计划中进行评估，但United Therapeutics打算在完成TETON研究和任何FDA要求后寻求FDA批准将Tyvaso-DPI标签扩展至包括IPF和PPF桥接研究。

About TETON PPF

关于TETON PPF

The TETON PPF study is a 698-patient, multicenter, randomized, double-blind, placebo-controlled phase 3 registration study to evaluate the safety and efficacy of nebulized Tyvaso in subjects with progressive pulmonary fibrosis (PPF) over a 52-week period. This third registration study is part of the global TETON program evaluating nebulized Tyvaso for the treatment of idiopathic pulmonary fibrosis (IPF) and PPF and will be conducted at sites globally..

TETON PPF研究是一项698名患者，多中心，随机，双盲，安慰剂对照的3期注册研究，旨在评估雾化Tyvaso在52周内进行性肺纤维化（PPF）患者的安全性和有效性。这项第三次注册研究是全球TETON计划的一部分，该计划评估雾化Tyvaso治疗特发性肺纤维化（IPF）和PPF，并将在全球各地进行。。

Subjects will be randomly allocated 1:1 to receive nebulized Tyvaso or placebo. All subjects will initiate nebulized Tyvaso or placebo at a dose of three breaths administered four times daily (QID) and will titrate to a target dosing regimen of 12 breaths QID. Study drug doses may be titrated up as tolerated, until the target dose or maximum clinically tolerated dose is achieved..

受试者将以1:1随机分配接受雾化Tyvaso或安慰剂。所有受试者将以每天四次（QID）施用三次呼吸的剂量启动雾化的Tyvaso或安慰剂，并将滴定至12次呼吸QID的目标给药方案。研究药物剂量可以按耐受性滴定，直到达到目标剂量或最大临床耐受剂量。。

The primary endpoint of the study is the change in FVC from baseline to week 52. Secondary endpoints include: (1) time to clinical worsening; (2) time to first acute exacerbation of interstitial lung disease (ILD); (3) overall survival at week 52; (4) change in percent predicted FVC from baseline to week 52; (5) change in the King’s Brief Interstitial Lung Disease questionnaire; and (6) change in the diffusing capacity of the lungs for carbon monoxide..

研究的主要终点是FVC从基线到第52周的变化。次要终点包括：（1）临床恶化的时间；（2） 首次急性加重间质性肺病（ILD）的时间；（3） 第52周总生存率；（4） 从基线到第52周的预测FVC百分比变化；（5） 改变国王简要间质性肺病问卷；和（6）改变肺对一氧化碳的扩散能力。。

Other data collected in the study will include the plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and supplemental oxygen use. Safety assessments include adverse event and serious adverse event monitoring, vital signs, clinical laboratory parameters, and electrocardiogram parameters..

研究中收集的其他数据将包括血浆N末端前脑利钠肽（NT-proBNP）浓度和补充氧气使用。安全性评估包括不良事件和严重不良事件监测，生命体征，临床实验室参数和心电图参数。。

About PPF

PPF

Progressive pulmonary fibrosis (PPF) is a group of interstitial lung disease (ILD) conditions that exhibit progressive, self-sustaining fibrosis, and display a similar disease course to idiopathic pulmonary fibrosis (IPF). PPF includes idiopathic interstitial pneumonias (other than IPF), autoimmune ILDs, chronic fibrosing hypersensitivity pneumonitis, and fibrotic ILDs related to environmental or occupational exposure.

进行性肺纤维化（PPF）是一组间质性肺病（ILD）病症，其表现出进行性，自我维持的纤维化，并且显示与特发性肺纤维化（IPF）类似的疾病过程。PPF包括特发性间质性肺炎（IPF除外），自身免疫性ILD，慢性纤维化超敏反应性肺炎和与环境或职业暴露有关的纤维化ILD。

It is estimated that 13% to 40% of patients with these various ILDs will go on to develop PPF1. Patients with PPF exhibit decreased lung function, poor quality of life, and increased mortality despite usual treatments for the underlying ILD. Estimates for median transplant free survival and overall survival are approximately 2.9 years and 3.7 years, respectively.2,3 Further, United Therapeutics estimates there are up to 60,000 PPF patients in the United States..

据估计，这些不同ILD患者中有13%至40%将继续发展PPF1。尽管通常对潜在的ILD进行治疗，但PPF患者的肺功能下降，生活质量下降，死亡率增加。中位无移植生存期和总生存期的估计分别约为2。9年和3。7年.2,3此外，United Therapeutics估计美国有多达60000名PPF患者。。

About Tyvaso® Inhalation Solution and Tyvaso DPI® Inhalation Powder

关于Tyvaso®吸入溶液和Tyvaso DPI®吸入粉

INDICATION

指示

TYVASO (treprostinil) Inhalation Solution and TYVASO DPI (treprostinil) Inhalation Powder are prostacyclin mimetics indicated for the treatment of:

TYVASO（曲前列环素）吸入溶液和TYVASO DPI（曲前列环素）吸入粉末是前列环素模拟物，用于治疗：

Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies with TYVASO establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%)..

肺动脉高压（PAH；WHO组1）以提高运动能力。TYVASO建立有效性的研究主要包括NYHA功能III级症状和特发性或遗传性PAH（56%）或与结缔组织病相关的PAH（33%）的病因。。

The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities.

在4小时的最小推荐给药间隔内效果减弱；可以针对计划的活动调整治疗时间。

While there are long-term data on use of treprostinil by other routes of administration, nearly all clinical experience with inhaled treprostinil has been on a background of an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor. The controlled clinical experience with TYVASO was limited to 12 weeks in duration..

虽然有关于通过其他给药途径使用曲前列环素的长期数据，但几乎所有吸入曲前列环素的临床经验都是在内皮素受体拮抗剂（ERA）和/或5型磷酸二酯酶（PDE-5）抑制剂。TYVASO的受控临床经验限制在12周内。。

Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study with TYVASO establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%)..

与间质性肺病相关的肺动脉高压（PH-ILD；WHO组3）可改善运动能力。TYVASO建立有效性的研究主要包括特发性间质性肺炎（IIP）病因（45%），包括特发性肺纤维化（IPF），合并肺纤维化和肺气肿（CPFE）（25%）和WHO组3结缔组织病（22%））。。

IMPORTANT SAFETY INFORMATION

重要的安全信息

WARNINGS AND PRECAUTIONS

警告和注意事项

TYVASO and TYVASO DPI are pulmonary and systemic vasodilators. In patients with low systemic arterial pressure, either product may produce symptomatic hypotension.

TYVASO和TYVASO DPI是肺和全身血管扩张剂。在全身动脉压低的患者中，任何一种产品都可能产生症状性低血压。

Both products inhibit platelet aggregation and increase the risk of bleeding.

两种产品均抑制血小板聚集并增加出血风险。

Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness..

共同施用细胞色素P450（CYP）2C8酶抑制剂（例如吉非贝齐）可增加对曲前列环素的暴露（Cmax和AUC）。CYP2C8酶诱导剂（例如利福平）的共同施用可以减少对曲前列环素的暴露。暴露增加可能会增加与曲前列环素给药相关的不良事件，而暴露减少可能会降低临床疗效。。

Like other inhaled prostaglandins, TYVASO and TYVASO DPI may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with TYVASO and TYVASO DPI..

像其他吸入前列腺素一样，TYVASO和TYVASO DPI可能引起急性支气管痉挛。患有哮喘或慢性阻塞性肺病（COPD）或其他支气管高反应性的患者支气管痉挛的风险增加。确保在使用TYVASO和TYVASO DPI治疗之前和期间对这些患者进行反应性气道疾病的最佳治疗。。

DRUG INTERACTIONS/SPECIFIC POPULATIONS

药物相互作用/特定人群

The concomitant use of either product with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension.

同时使用利尿剂，抗高血压药或其他血管扩张剂的产品可能会增加症状性低血压的风险。

Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil.

用曲前列环素（曲前列环素二胺）口服制剂进行的人体药代动力学研究表明，细胞色素P450（CYP）2C8酶抑制剂吉非贝齐的共同给药增加了对曲前列环素的暴露（Cmax和AUC）。CYP2C8酶诱导剂利福平的共同施用减少了对曲前列环素的暴露。

It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8..

目前尚不清楚吸入途径中曲前列环素的安全性和有效性是否被CYP2C8的抑制剂或诱导剂所改变。。

Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production..

孕妇使用曲前列环素的有限病例报告不足以告知药物相关的不良发育结局风险。然而，肺动脉高压与孕产妇和胎儿死亡风险增加有关。没有关于人乳中曲前列环素存在，对母乳喂养婴儿的影响或对产奶量的影响的数据。。

Safety and effectiveness in pediatric patients have not been established.

儿科患者的安全性和有效性尚未确定。

Across clinical studies used to establish the effectiveness of TYVASO in patients with PAH and PH‑ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety profile observed in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy..

在用于确定TYVASO在PAH和PH-ILD患者中的有效性的临床研究中，招募了268名（47.8%）65岁及以上的患者。在老年患者中观察到的治疗效果和安全性与年轻患者相似。通常，老年患者的剂量选择应谨慎，以反映肝，肾或心脏功能障碍以及伴随疾病或其他药物治疗的频率更高。。

ADVERSE REACTIONS

不良反应

Pulmonary Arterial Hypertension (WHO Group 1)

肺动脉高压（WHO组1）

In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most common adverse reactions seen with TYVASO in ≥4% of PAH patients and more than 3% greater than placebo were cough (54% vs 29%), headache (41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), flushing (15% vs <1%), and syncope (6% vs <1%).

在235例PAH患者（WHO组1和几乎所有NYHA功能III级）的12周安慰剂对照研究（TRIUMPH I）中，TYVASO在≥4%的PAH患者中最常见的不良反应是咳嗽（54%vs 29%），头痛（41%vs 23%），咽喉刺激/咽喉痛（25%vs 14%），恶心（19%vs 11%），潮红（15%vs<1%），和晕厥（6%vs<1%）。

In addition, adverse reactions occurring in ≥4% of patients were dizziness and diarrhea..

此外，≥4%的患者出现不良反应，包括头晕和腹泻。。

In a 3-week, open-label, single-sequence, safety and tolerability study (BREEZE) conducted in 51 patients on stable doses of TYVASO who switched to a corresponding dose of TYVASO DPI, the most commonly reported adverse events seen with TYVASO DPI in ≥4% of PAH patients during the 3-week treatment phase included cough (35.3%), headache (15.7%), dyspnea (7.8%), and nausea (5.9%)..

在一项为期3周的开放标签单序列安全性和耐受性研究（BREEZE）中，51名稳定剂量的TYVASO患者转为相应剂量的TYVASO DPI，最常见的不良事件是TYVASO DPI在3周治疗阶段≥4%的PAH患者包括咳嗽（35.3%），头痛（15.7%），呼吸困难（7.8%）和恶心（5.9%）。。

Pulmonary Hypertension Associated with ILD (WHO Group 3)

与ILD相关的肺动脉高压（WHO组3）

In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions with TYVASO were similar to the experience in studies of PAH.

在326例PH-ILD患者（WHO第3组）的16周安慰剂对照研究（增加）中，TYVASO的不良反应与PAH研究的经验相似。

Please see Full Prescribing Information for TYVASO or TYVASO DPI, Instructions for Use manuals for TD-100 and TD-300 TYVASO® Inhalation System and TYVASO DPI™ Inhalation Powder, and additional information at www.TYVASOHCP.com or call 1‑877‑UNITHER (1-877-864-8437).

请参阅TYVASO或TYVASO DPI的完整处方信息，TD-100和TD-300Tyvaso®吸入系统和TYVASO DPI的使用手册说明™ 吸入粉末，以及其他信息，请访问www.TYVASOHCP.com或致电1-877-UNITHER（1-877-864-8437）。

TYVISIhcpMAY2022

2022年5月

United Therapeutics: Enabling Inspiration

联合治疗：激发灵感

At United Therapeutics, our vision and mission are one. We use our enthusiasm, creativity, and persistence to innovate for the unmet medical needs of our patients and to benefit our other stakeholders. We are bold and unconventional. We have fun; we do good. We are the first publicly traded biotech or pharmaceutical company to take the form of a public benefit corporation.

在United Therapeutics，我们的愿景和使命就是其中之一。我们运用我们的热情，创造力和毅力为患者未满足的医疗需求进行创新，并使我们的其他利益相关者受益。我们大胆而非常规。我们很开心；我们很好。我们是第一家以公益性公司形式上市的生物技术或制药公司。

Our public benefit purpose is to provide a brighter future for patients through the development of novel pharmaceutical therapies; and technologies that expand the availability of transplantable organs..

我们的公共利益目的是通过开发新的药物疗法为患者提供更光明的未来；和扩大可移植器官可用性的技术。。

You can learn more about what it means to be a PBC here: unither.com/pbc.

您可以在这里了解更多关于成为PBC的意义：unither.com/PBC。

Forward-looking Statements

前瞻性声明

Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements regarding the planned enrollment, conduct, and design of the TETON 1, TETON 2, and TETON PPF clinical studies, the potential for Tyvaso to become a treatment option for patients with fibrotic lung disease, our plans to seek IPF and PPF indications for the Tyvaso DPI label, and our goals of innovating for the unmet medical needs of our patients and to benefit our other stakeholders and furthering our public benefit purpose of developing novel pharmaceutical therapies and technologies that expand the availability of transplantable organs.

本新闻稿中包含的非历史性陈述是1995年“私人证券诉讼改革法”含义内的“前瞻性陈述”。前瞻性声明包括有关TETON 1，TETON 2和TETON PPF临床研究的计划注册，实施和设计的声明，Tyvaso成为纤维化肺病患者治疗选择的潜力，我们计划为Tyvaso DPI标签寻求IPF和PPF适应症，以及我们为患者未满足的医疗需求进行创新的目标，并使我们的其他利益相关者受益，并促进我们的公共利益目标，即开发新的药物疗法和技术，扩大可移植器官的可用性。

These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K.

这些前瞻性陈述存在某些风险和不确定性，例如我们向证券交易委员会提交的定期报告中所述的风险和不确定性，可能导致实际结果与预期结果大不相同。因此，这些前瞻性陈述符合我们向美国证券交易委员会提交的定期报告和文件中规定的警示性陈述，警示性语言和风险因素，包括我们最近关于表格10-K的年度报告，季度报告表格10-Q和表格8-K的当前报告。

We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of October 31, 2023, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason..

我们要求保护1995年“私人证券诉讼改革法”中包含的安全港以进行前瞻性声明。我们自2023年10月31日起提供此信息，并且不承担更新或修改本新闻稿中包含的信息的义务，无论是由于新信息，未来事件还是任何其他原因。。

TYVASO and TYVASO DPI are registered trademarks of United Therapeutics Corporation.

TYVASO和TYVASO DPI是United Therapeutics Corporation的注册商标。

1 Olson AL, Patnaik P, Hartmann N, et al. Prevalence and incidence of chronic fibrosing interstitial lung diseases with a progressive phenotype in the United States estimated in a large claims database analysis. Adv Ther. 2021;38:4100-4114.

1 Olson AL，Patnaik P，Hartmann N等人。在大型索赔数据库分析中估计的美国慢性纤维化间质性肺病的进展性表型的患病率和发病率。Adv Ther。2021;38:4100-4114.

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3 Cottin V, Teague R, Nicholson L, et al. The burden of progressive-fibrosing interstitial lung disease. Front Med. 2022;9:799912.

3 Cottin V，Teague R，Nicholson L，et al。进行性纤维化间质性肺病的负担。Front Med.2022；9:799912.