United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug application (IND) to initiate a clinical study of the company’s investigational UKidney™ derived from a 10 gene-edited source pig. The study will enroll an initial cohort of six end-stage renal disease (ESRD) patients, expanding to up to 50 participants, and is intended to support a Biologics License Application (BLA) with the FDA

United Therapeutics Corporation 今天宣布，美国食品药品管理局 ( FDA ) 已批准其新药临床试验申请 ( IND )，以启动该公司从 10 个基因编辑源猪中提取的 UKidney™ 临床试验。该研究将招募首批 6 名终末期肾病 ( ESRD ) 患者，并将扩大至 50 名参与者，旨在支持向 FDA 提交的 生物制品许可申请 ( BLA )。

United Therapeutics expects the first xenotransplant in this trial to be performed around mid-year 2025.

联合治疗公司预计，该试验中的第一次异种移植将在2025年年中左右进行。

According to the American Kidney Fund, more than 557,000 patients in the U.S. are on dialysis to filter their blood when their kidneys are no longer able to do so

根据美国肾脏基金会的数据，美国有55.7万多名患者正在进行透析，以在肾脏无法进行透析时过滤血液

. A 2009 study estimated that 52% of kidney transplant candidates who were at least 60 years of age when placed on the transplant waitlist die within five years before receiving a transplant

2009年的一项研究估计，52%被列入移植候补名单的60岁以上的肾移植候选人在接受移植前五年内死亡

. United Therapeutics believes that xenotransplantation offers a therapeutic alternative to dialysis.

联合治疗公司认为，异种移植为透析提供了一种治疗替代方案。

“Clearance of our IND for this first-ever clinical trial of a xenokidney represents a significant step forward in our relentless mission to expand the availability of transplantable organs,” said

他说：“我们首次对异种肾进行临床试验的IND获得批准，标志着我们在扩大可移植器官可用性的不懈使命中迈出了重要的一步。”

Leigh Peterson, Ph.D.

Leigh Peterson博士。

, Executive Vice President, Product Development and Xenotransplantation at United Therapeutics. “Our goal is to increase the availability of transplantable organs to offer a therapeutic alternative to a lifetime on dialysis for a large population of patients who are unlikely to receive an allogeneic.

，联合治疗公司产品开发和异种移植执行副总裁。“我们的目标是增加可移植器官的可用性，为不太可能接受同种异体移植的大量患者提供终身透析的治疗替代方案。

This first-in-human clinical study aims to assess safety and efficacy of the UKidney in two groups of participants:

这项首次人体临床研究旨在评估UKidney在两组参与者中的安全性和有效性：

ESRD patients who have been assessed and determined to be ineligible for a conventional allogeneic kidney transplant for medical reasons; and

ESRD患者因医学原因被评估并确定不符合常规同种异体肾移植的资格；和

ESRD patients who have been on the kidney transplant waitlist but are more likely to die or go untransplanted than receive a deceased donor kidney transplant within five years.

已列入肾移植候补名单但在五年内死亡或未移植的ESRD患者比接受已故供体肾移植的患者更有可能死亡或未移植。

“Eliminating the need for dialysis or limiting time on dialysis may improve survival for many patients with ESRD,” said

“消除透析需求或限制透析时间可能会提高许多ESRD患者的生存率，”他说

Vice President, Global Regulatory Affairs at United Therapeutics. “We appreciate the productive collaboration with the FDA in advancing our efforts to bring this potentially revolutionary therapeutic option to the hundreds of thousands of ESRD patients.”

联合治疗公司全球监管事务副总裁。“我们感谢与FDA的卓有成效的合作，推动我们努力为数十万ESRD患者带来这种潜在的革命性治疗选择。”

About the Study

关于这项研究

Study Design

研究设计

The study is a multicenter, open-label, safety and efficacy study and is intended to support FDA approval of a BLA. The 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.

该研究是一项多中心，开放标签，安全性和有效性研究，旨在支持FDA批准BLA。该研究设计为1/2/3期联合试验（有时称为“无阶段”研究），以无缝评估安全性和有效性，而无需进行通常与常规药物批准相关的单独的1期，2期和3期研究。

Participants will receive a UKidney transplant followed by a 24-week post-transplant follow-up period, including the evaluation of all study endpoints and safety assessments. After the 24-week post-transplant follow-up period, participants who received a UKidney will continue to be followed for the rest of their lives, including for survival, UKidney function, and monitoring for zoonotic infections.

。在移植后24周的随访期后，接受UKidney治疗的参与者将在其余生中继续接受随访，包括生存，UKidney功能和人畜共患感染监测。

Efficacy Endpoints

疗效终点

Efficacy endpoints include participant survival rate, UKidney survival rate, change in measured glomerular filtration rate

疗效终点包括参与者生存率、UKidney生存率、测量的肾小球滤过率变化

, and change in quality of life in participants

，以及参与者生活质量的变化

at 24 weeks post-transplant. Overall survival time of participants receiving a UKidney and overall survival time of the UKidneys themselves are also efficacy endpoints.

移植后24周。接受UKidney的参与者的总生存时间和UKidney本身的总生存时间也是疗效终点。

Safety Endpoints

安全端点

Safety endpoints include the incidence of adverse events and serious adverse events, all-cause mortality, and the incidence of proteinuria

安全性终点包括不良事件和严重不良事件发生率、全因死亡率和蛋白尿发生率

Cohort-Based Design

基于队列的设计

The first cohort will consist of six transplants at two centers. There will be a 12-week waiting period between the first and second transplants. After the initial cohort reaches at least 12 weeks post-transplant, safety and efficacy data will be reviewed by an independent Data Monitoring Committee to determine if the study should proceed to the next cohort.

第一组将由两个中心的六个移植组成。第一次和第二次移植之间将有12周的等待期。在最初的队列达到移植后至少12周后，安全性和有效性数据将由独立的数据监测委员会进行审查，以确定该研究是否应进入下一个队列。

In addition, United Therapeutics intends to engage with the FDA after the first six transplants are completed. If safety and efficacy results are supportive, the sample size will be increased to a total of up to 50 participants to enable the study to support registration, with additional transplant centers expected to be added to the study..

此外，联合治疗公司打算在前六次移植完成后与FDA合作。如果安全性和有效性结果得到支持，样本量将增加到总共50名参与者，以使研究能够支持注册，预计将在研究中增加额外的移植中心。。

Additional Key Participation Criteria

其他关键参与标准

Additional key participation criteria include an age of 55 to 70 years old, a diagnosis of ESRD, and at least six months on hemodialysis. Participants will be screened using a crossmatch assay to assess expected immunological compatibility with the UKidney. Participants must not need multiple organ transplants; must not have severe medical co-morbidities, including but not limited to advanced cardiovascular disease, severe peripheral vascular disease, severe neurological disease, chronic pulmonary disease, and uncontrolled diabetes; and must not have a history of medical noncompliance that may preclude adherence to the demands and requirements of xenotransplantation..

其他关键参与标准包括年龄在55至70岁之间，诊断为ESRD，以及至少六个月的血液透析。参与者将使用交叉配型分析进行筛选，以评估与UKidney的预期免疫相容性。参与者不得需要多器官移植；不得有严重的医学合并症，包括但不限于晚期心血管疾病，严重的外周血管疾病，严重的神经系统疾病，慢性肺病和不受控制的糖尿病；并且不得有可能妨碍遵守异种移植要求和要求的医疗不合规史。。

Full inclusion and exclusion criteria for this study will be provided in a future listing on the clinicaltrials.gov website.

这项研究的完整纳入和排除标准将在clinicaltrials.gov网站上的未来列表中提供。

About End-Stage Renal Disease

关于终末期肾病

According to the American Kidney Fund, there are approximately 808,000 patients with kidney failure in the United States and more than 557,000 patients on dialysis, approximately 93,000 of whom are on the U.S. kidney transplant waiting list. Only 21,000 deceased donor kidney transplants occurred in 2023.

根据美国肾脏基金会的数据，美国约有808000名肾衰竭患者和557000多名透析患者，其中约93000人在美国肾移植等待名单上。2023年仅发生21000例死亡供肾移植。

. A 2021 study found that three years after starting dialysis, only 12% of patients had been placed on an Organ Procurement and Transplant Network kidney transplant waitlist while more than 40% died

2021年的一项研究发现，开始透析三年后，只有12%的患者被列入器官采购和移植网络肾移植候补名单，而超过40%的患者死亡

About UKidney

关于UKidney

United Therapeutics’ xenokidney, known by the proposed trade name UKidney, is an investigational xenokidney from a pig with 10 gene edits. Six human genes are added to the pig genome to facilitate immunological acceptance and compatibility of the organ in the human recipient, while four porcine genes are inactivated: three that contribute to porcine organ rejection in humans and one that can cause organ growth..

联合治疗公司（United Therapeutics）的异种肾（Xenokeny）是一种来自猪的研究性异种肾，具有10个基因编辑。六个人类基因被添加到猪基因组中，以促进人类受体器官的免疫接受和相容性，而四个猪基因被灭活：三个导致人类猪器官排斥，一个导致器官生长。。

United Therapeutics: Enabling Inspiration

联合疗法：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 (.

在联合治疗公司，我们的愿景和使命是一体的。我们利用我们的热情、创造力和毅力来创新，以满足患者未满足的医疗需求，并使其他利益相关者受益。我们大胆而非传统。我们很开心，我们做得很好。我们是第一家以公益公司形式上市的生物技术或制药公司（。