NEWARK, California, OSAKA, Japan and CAMBRIDGE, Massachusetts, March 3, 2025 – Protagonist Therapeutics, Inc. (“Protagonist”) (NASDAQ:PTGX) and Takeda (TSE:4502/NYSE:TAK) today announced positive topline results for the Phase 3 VERIFY study, in which phlebotomy-dependent patients with polycythemia vera (PV) were randomized to treatment with either rusfertide or placebo, as an add-on to standard of care treatment.

加利福尼亚州纽瓦克市、日本大阪市及马萨诸塞州剑桥市，2025年3月3日 – Protagonist Therapeutics, Inc.（“Protagonist”）（纳斯达克股票代码：PTGX）和武田制药（东京证券交易所股票代码：4502/纽约证券交易所股票代码：TAK）今天宣布了3期VERIFY研究的积极顶线结果，在该研究中，依赖静脉切开放血术的真性红细胞增多症（PV）患者被随机分配接受Rusfertide或安慰剂治疗，作为标准治疗的附加治疗。

The study met its primary endpoint and all four key secondary endpoints. Rusfertide is a first-in-class investigational hepcidin mimetic peptide therapeutic, which has received Orphan Drug designation and Fast Track designation from the U.S. Food & Drug Administration (FDA)..

该研究达到了其主要终点和所有四个关键次要终点。Rusfertide 是一种首创的在研类铁调素肽治疗药物，已获得美国食品药品监督管理局 (FDA) 的孤儿药资格认定和快速通道资格认定。

Key findings from the study include:

研究的主要发现包括：

“The positive results of the Phase 3 VERIFY study across the primary and all key secondary endpoints provide compelling evidence of the potential for rusfertide as a first-in-class erythrocytosis-specific agent to address unmet medical needs in patients with PV who are unable to achieve adequate hematocrit control despite standard of care treatments,” said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist.

“三期验证研究在主要终点和所有关键次要终点的积极结果为rusfertide作为一种首创的红细胞增多症特异性药物提供了有力证据，证明其有望满足那些尽管接受标准治疗仍无法实现足够红细胞压积控制的PV患者未被满足的医疗需求，”Protagonist首席医学官Arturo Molina医学博士说道。

“We plan to submit additional details of these promising results for presentation at upcoming medical conferences in 2025. We are immensely grateful to the patients, study staff and principal investigators who made the VERIFY study possible.”.

“我们计划在2025年的医学会议上提交这些有希望的结果的更多细节。我们非常感谢使VERIFY研究成为可能的患者、研究人员和主要研究者。”

Patients with PV are at increased risk for life-threatening cardiovascular and thrombotic events. Many patients with PV require regular phlebotomy, a process of removing blood to manage elevated hematocrit levels caused by an excess of red blood cells, as well as treatment with cytoreductive therapies.

真性红细胞增多症（PV）患者发生危及生命的心血管和血栓事件的风险增加。许多 PV 患者需要定期进行放血术，即通过去除血液来控制因红细胞过多导致的高血细胞比容水平，同时还需要接受细胞减灭疗法的治疗。

Phlebotomy can be burdensome and exacerbate symptoms, including severe fatigue, visual disturbances and iron deficiency, which impact patients’ quality of life. The reduction of hematocrit below 45% is a primary treatment goal for patients with PV as recommended by current treatment guidelines..

放血疗法可能会加重负担并加剧症状，包括严重疲劳、视力障碍和缺铁，这些都会影响患者的生活质量。根据现行治疗指南的建议，将红细胞比容降低至45%以下是PV患者的主要治疗目标。

“We are encouraged by these results and excited about the potential of rusfertide to help patients living with PV. These patients may experience a high treatment burden, and severe symptoms can impact their quality of life,” said Andy Plump, M.D., Ph.D., President of R&D at Takeda. “We are deeply committed to bringing additional treatment options to those living with blood cancers, including myeloid cancers such as PV.”.

“这些结果让我们备受鼓舞，我们对rusfertide帮助真性红细胞增多症（PV）患者的潜力感到兴奋。这些患者可能面临较高的治疗负担，严重症状会影响他们的生活质量，”武田制药研发总裁Andy Plump博士表示。“我们坚定致力于为血液癌症患者，包括骨髓增生性癌症如PV患者，带来更多的治疗选择。”

“The totality of impressive clinical data to date shows that rusfertide has the potential for meaningful positive impact on the lives of patients with PV,” said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. “We look forward to working with our partner, Takeda, to submit our findings to the regulatory agencies.

“迄今为止令人印象深刻的临床数据总体显示，rusfertide 有潜力对 PV 患者的生活产生有意义的积极影响，”Protagonist 总裁兼首席执行官 Dinesh V. Patel 博士表示。“我们期待与我们的合作伙伴武田一起，向监管机构提交我们的研究结果。”

Today’s study results also mark a critical inflection point in Protagonist’s decade long journey in the hepcidin program and further validates our platform and expertise in innovating highly differentiated peptide-based medicines to fulfill unmet medical needs.”.

今天的研究结果也标志着Protagonist在hepcidin项目十年征程中的一个关键转折点，并进一步验证了我们创新高度差异化肽类药物以满足未竟医疗需求的平台和专业能力。

Under the license and collaboration agreement between Protagonist and Takeda, Protagonist earns a $25 million milestone payment following these positive results. The milestone is payable following completion of the VERIFY clinical study report.

根据Protagonist与武田之间的许可和合作协议，Protagonist在这些积极结果之后获得了2500万美元的里程碑付款。该里程碑款项将在VERIFY临床研究报告完成后支付。

The impact on Takeda’s financial results for the fiscal year ending March 31, 2025 (FY2024), following the study results, is immaterial.

由于研究结果对截至2025年3月31日的财年（2024财年）武田财务业绩的影响并不重大。

Protagonist will host a conference call and webcast, for which details can be found below.

主角将主持电话会议和网络直播，详情如下。

The Phase 3 VERIFY trial (NCT05210790) is an ongoing, three-part, global, randomized, placebo-controlled trial evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period. The trial is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy dependent despite standard of care treatment, which could include hydroxyurea, interferon and/or ruxolitinib.

第三阶段VERIFY试验（NCT05210790）是一项正在进行的、分为三部分的全球随机、安慰剂对照试验，在293名真性红细胞增多症患者中评估rusfertide，试验周期为156周。该试验正在评估每周一次皮下自我注射rusfertide在对标准治疗（可能包括羟基脲、干扰素和/或鲁索替尼）依赖放血术但仍未控制住红细胞比容的患者中的有效性和安全性。

The primary endpoint of the study was the proportion of patients achieving a response during weeks 20-32, which was defined as the absence of “phlebotomy eligibility.” To meet phlebotomy eligibility, patients in the study were required to have: confirmed hematocrit ≥45% that was ≥3% higher than their baseline hematocrit value, or hematocrit ≥48%..

研究的主要终点是患者在第20-32周期间达到反应的比例，反应定义为无“符合放血条件”。在研究中，符合放血条件的患者需满足以下要求：确认的红细胞压积≥45%，且比其基线红细胞压积值高≥3%，或红细胞压积≥48%。

All patients have completed their participation in the randomized, placebo-controlled portion of the trial evaluating the efficacy and safety of rusfertide plus current treatment versus placebo plus current treatment and are now in the open-label portions of the trial.

所有患者均已完成了他们在评估 rusfertide 加当前治疗对比安慰剂加当前治疗的有效性和安全性的随机、安慰剂对照试验部分的参与，目前正处于试验的开放标签阶段。

Protagonist Therapeutics is a discovery through late-stage development biopharmaceutical company. Two novel peptides derived from Protagonist's proprietary discovery platform are currently in advanced Phase 3 clinical development, with New Drug Application submissions to the FDA expected in 2025. Icotrokinra (formerly, JNJ-2113) is a first-in-class investigational targeted oral peptide that selectively blocks the Interleukin-23 receptor (“IL-23R”) which is licensed to JNJ Innovative Medicines (“JNJ”), formerly Janssen Biotech, Inc.

Protagonist Therapeutics是一家从药物发现到后期开发的生物制药公司。目前，由Protagonist专有发现平台衍生的两种新型肽类化合物已进入高级第三阶段临床开发，预计将于2025年向FDA提交新药申请。Icotrokinra（曾用名JNJ-2113）是一种首创的研究性靶向口服肽，可选择性阻断白细胞介素-23受体（“IL-23R”），该药物已授权给JNJ创新药物（“JNJ”，前身为杨森生物技术公司）。

Following icotrokinra's joint discovery by Protagonist and JNJ scientists pursuant to the companies' IL-23R collaboration, Protagonist was primarily responsible for development of icotrokinra through Phase 1, with JNJ assuming responsibility for development in Phase 2 and beyond. Rusfertide, a mimetic of the natural hormone hepcidin, is currently in Phase 3 development for the rare blood disorder polycythemia vera (PV).

在Protagonist和JNJ的科学家根据两家公司关于IL-23R的合作共同发现icotrokinra后，Protagonist主要负责通过第一阶段的icotrokinra开发，而JNJ则承担了第二阶段及以后的开发责任。Rusfertide是一种模拟天然激素铁调素的药物，目前正处于针对罕见血液病真性红细胞增多症（PV）的第三阶段开发中。

Rusfertide is being co-developed and will be co-commercialized with Takeda Pharmaceuticals pursuant to a worldwide collaboration and license agreement entered into in 2024 under which the Company remains primarily responsible for development through NDA filing. The Company also has a number of pre-clinical stage oral drug discovery programs addressing clinically and commercially validated targets, including IL-17 oral peptide antagonist PN-881, oral hepcidin program, and oral obesity program..

Rusfertide正在与武田制药共同开发，并将根据2024年达成的全球合作和许可协议共同商业化，根据该协议，公司仍然主要负责直至新药申请（NDA）提交的开发工作。公司还拥有多个针对临床和商业已验证靶点的临床前阶段口服药物发现项目，包括IL-17口服肽拮抗剂PN-881、口服铁调素项目以及口服肥胖症项目。

Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines.

武田专注于为人类创造更好的健康，并为世界带来更光明的未来。我们致力于在核心治疗和业务领域发现并提供改变生命的疗法，包括胃肠病与炎症、罕见病、血浆衍生疗法、肿瘤学、神经科学和疫苗。

Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet.

与我们的合作伙伴一起，我们旨在通过动态且多样化的研发管线改善患者体验，并推进治疗选择的新领域。作为一家总部位于日本的领先价值观导向、研发驱动的生物制药公司，我们始终以对患者、员工和地球的承诺为指引。

Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com..

我们遍布约80个国家和地区的员工以我们的宗旨为动力，并立足于两个多世纪以来定义我们的价值观。欲了解更多信息，请访问www.takeda.com。