Verdinexor

SHANGHAI and HONG KONG, June 26, 2022 /PRNewswire/ -- Antengene Corporation Limited ( "Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, today announced that it has entered into a clinical trial collaboration with BeiGene to evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of selinexor in combination with BeiGene's anti-PD-1 checkpoint inhibitor, tislelizumab. This multi-center, open-label Phase I/II trial will evaluate the investigational combination as a potential treatment option for patients with T and NK-cell lymphoma. "We are delighted to partner with BeiGene, a company that strives for innovation and excellence, and is committed to developing best-in-class or first-in-class anti-cancer therapies for patients across the globe. These qualities are very similar to those of our vision at Antengene," said Dr. Jay Mei, Antengene's Founder, Chairman and CEO. "We look forward to advancing the combination of selinexor and tislelizumab to clinical development. With good data we will be able to bring this treatment regimen to patients with T and NK-cell lymphoma, diseases that are endemic in Asia but underserved by current therapies." "At Antengene, we believe that the combinational use of immuno-oncology drugs and Selective Inhibitor of Nuclear Export (SINE) compounds possesses huge potential as novel treatment regimens for cancer patients," said Dr. Kevin Lynch, Antengene's Chief Medical Officer. "The mechanism of action of selinexor in inhibiting the nuclear export protein XPO1 facilitates the intranuclear accumulation of tumor suppressors, making it a good partner in multiple combination treatment regimens. Preclinical research we conducted demonstrated that selinexor combined with a checkpoint inhibitor increased anti-tumor activity in multiple tumor models. In addition, deep and durable responses were also seen in multiple case reports of patients with T and NK-cell lymphoma treated with selinexor in combination with an anti-PD-1 checkpoint inhibitor. We hope to confirm that selinexor can synergize with tislelizumab to deliver an effective treatment regimen and help address the huge unmet medical needs in T and NK-cell lymphoma in the Asia Pacific regions and around the world." continued Dr. Lynch. Tislelizumab is a PD-1 inhibitor designed to help aid the body's immune cells to detect and fight tumors. Tislelizumab, a humanized monoclonal antibody, is specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. About T and NK-Cell Lymphoma T and NK-cell lymphoma is a set of heterogeneous diseases, accounting for 25-30% of Non-Hodgkin Lymphoma (NHL) cases in China and only about 10% in USA and Europe. There has been little improvement in the past decade when compared to B-cell Non-Hodgkin Lymphoma (B-NHL) as 5-year overall survival rate was only 30% in most common subtypes[1]. The unmet medical needs remain as agents with new mechanism of action to be explored and possibility to improve the treatment paradigm for the disease. About the SINE Compounds Selective Inhibitor of Nuclear Export (SINE) compounds are inhibitors of the major nuclear export protein Exportin 1 (XPO1). Currently, there are three oral SINE compounds, ATG-010 (selinexor), ATG-016 (eltanexor), and ATG-527 (verdinexor), under clinical development. Antengene has obtained exclusive development and commercialisation rights from Karyopharm Therapeutics Inc. (Nasdaq: KPTI) to these three compounds in certain APAC markets. About XPOVIO® (Selinexor) XPOVIO® is the world's first approved orally-available, selective inhibitor of the nuclear export protein XPO1. It offers a novel mechanism of action, synergistic effects in combination regimens, fast onset of action, and durable responses. By blocking the nuclear export protein XPO1, XPOVIO® can promote the intranuclear accumulation and activation of tumor suppressor proteins and growth regulating proteins, and down-regulate the levels of multiple oncogenic proteins. XPOVIO® delivers its antitumor effects through three mechanistic pathways: 1) exerting antitumor effects by inducing the intranuclear accumulation of tumor suppressor proteins; 2) reducing the level of oncogenic proteins in the cytoplasm by inducing the intranuclear accumulation of oncogenic mRNAs; and 3) restoring hormone sensitivity by activating the glucocorticoid receptors (GR) pathway. To utilize its unique mechanism of actions, XPOVIO® is being evaluated for use in multiple combination regimens in a range of indications. At present, Antengene is conducting 10 clinical studies of XPOVIO® in mainland China for the treatment of relapsed/refractory hematologic malignancies and solid tumors (3 of these studies are being jointly conducted by Antengene and Karyopharm Therapeutics Inc. [Nasdaq:KPTI]). XPOVIO® is approved in South Korea for two indications: In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. As a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. XPOVIO® is approved in mainland China for one indication: In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received prior therapies and whose disease is refractory to at least one proteasome inhibitor, at least one immunomodulatory agent, and an anti-CD38 monoclonal antibody. XPOVIO® is approved in Australia for two indications: In combination with bortezomib and dexamethasone (XVd) for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy. In combination with dexamethasone (Xd) for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor (PI), at least one immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody (mAb). XPOVIO® is approved in Singapore for three indications: In combination with bortezomib and dexamethasone for treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy. In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. As a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy who are not eligible for haematopoietic cell transplant. About Antengene Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading commercial-stage R&D-driven global biopharmaceutical company focused on the discovery, development, manufacturing and commercialization of innovative first-in-class/best-in-class therapeutics for the treatment of hematologic malignancies and solid tumors, in realizing its vision of "Treating Patients Beyond Borders". Since 2017, Antengene has built a broad and expanding pipeline of 15 clinical and preclinical assets, of which 10 are global rights assets, and 5 came with rights for Asia Pacific markets including the Greater China region. To date, Antengene has obtained 24 investigational new drug (IND) approvals in the U.S. and Asia, and submitted 6 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for XPOVIO® (selinexor) already approved in mainland China, South Korea, Singapore and Australia. About BeiGene BeiGene is a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide. With a broad portfolio of more than 40 clinical candidates, we are expediting development of our diverse pipeline of novel therapeutics through our own capabilities and collaborations. We are committed to radically improving access to medicines for two billion more people by 2030. BeiGene has a growing global team of over 8,000 colleagues across five continents. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.

希维奥®（塞利尼索片）是一款口服型XPO1小分子抑制剂；百泽安®（替雷利珠单抗）是一款抗PD-1检查点抑制剂。中国上海和香港，2022年6月27日——德琪医药有限公司（简称“德琪医药”，香港交易所股票代码：6996.HK）今日宣布，公司已与百济神州达成协议，将联手开展旨在评估塞利尼索联合百济神州的抗PD-1检查点抑制剂百泽安®用于治疗T和NK细胞淋巴瘤的安全性、药代动力学、药效动力学和初步疗效的多中心、开放性I/II期研究。德琪医药创始人、董事长兼首席执行官梅建明博士表示：“我们很高兴能与百济神州合作。百济神州是一家立足于科学、不断创新进取，致力于为全球患者开发‘同类最佳’或‘同类第一’抗肿瘤药物的公司。他们努力的方向与德琪医药的战略愿景高度契合。我们将尽快启动塞利尼索联合百泽安®这一联合疗法的临床开发。T和NK细胞淋巴瘤是一种在亚洲区域性高发且存在巨大未被满足临床需求的疾病。如果试验数据积极，我们就能为T和NK细胞淋巴瘤患者提供一个新的治疗方案。”德琪医药首席医学官Kevin Lynch博士表示：“在德琪医药，我们相信将肿瘤免疫治疗药物与选择性核输出药物（SINE）的联用可为肿瘤患者的治疗带来具有巨大临床潜力的新型治疗方案。塞利尼索对于核输出蛋白XPO1的抑制机制，可促进肿瘤生长抑制蛋白的核内储留，这就赋予了该药物与多种药物联用的潜力。我们的临床前研究显示，塞利尼索联合检查点抑制剂在多个肿瘤模型中具有更高的抗肿瘤活性。此外，我们还在多个接受了塞利尼索联合抗PD-1检查点抑制剂治疗的T和NK细胞淋巴瘤患者中观察到深度且持久的缓解。我们希望能在研究中确认塞利尼索与百泽安®的协同效应，并为亚太地区乃至全球的T和NK细胞淋巴瘤患者提供一种有效且可满足其巨大临床需求的治疗方案。”百泽安®是抗PD-1抗体，药物设计的目的旨在支持身体的免疫细胞对肿瘤的检测和对抗。百泽安®作为人源化单克隆抗体的药物设计可以最大限度地减少与巨噬细胞中的Fcγ受体结合。临床前数据表明，巨噬细胞中的Fcγ受体结合之后会激活抗体依赖细胞介导杀伤T细胞，从而降低了PD-1抗体的抗肿瘤活性。关于T和NK细胞淋巴瘤T和NK细胞淋巴瘤是一种异质性疾病，它占中国所有非霍奇金淋巴瘤（NHL）病例的25%~30%，而在欧美该比例只有约10%。在过去十几年中，其治疗进展较B细胞非霍奇金淋巴瘤（B-NHL）而言极为有限，主要分型的5年总生存率只有30%[1]。目前，有多个具有全新作用机制和改变治疗现状潜力的药物正处在开发阶段，以解决该疾病尚未被满足的临床需求。关于SINE药物选择性核输出抑制剂（SINE）靶向作用于主要核输出蛋白Exportin 1（XPO1）。目前，有三款口服SINE药物正处于临床开发阶段，它们是ATG-010(塞利尼索)、ATG-016(eltanexor)和ATG-527(verdinexor)。德琪医药已经从Karyopharm Therapeutics Inc.（纳斯达克交易所股票代码：KPTI）公司获得了这三款药物在亚太区多个市场的独家开发和商业化权益。关于希维奥®（塞利尼索片）希维奥®是全球首个全新机制的口服选择性核输出蛋白（XPO1）抑制剂，具有“全新机制、协同增效、快速起效、持久缓解”四大特点。通过抑制核输出蛋白XPO1，希维奥®可促使肿瘤抑制蛋白和其他生长调节蛋白的核内储留和活化，并下调细胞浆内多种致癌蛋白水平。希维奥®发挥抗肿瘤作用机制的三条通路为：1）使抑癌蛋白在细胞核中明显聚集，再激活发挥抗肿瘤作用；2）使致癌基因mRNA滞留在细胞核，降低胞浆内致癌蛋白水平；3）激活糖皮质激素受体（GR）通路，恢复激素敏感性。基于其独特的作用机制，希维奥® 在不同疾病领域的多种联合疗法正在进行开发。目前，德琪医药正在中国大陆地区开展十项（其中三项由德琪医药与Karyopharm Therapeutics Inc. 公司[纳斯达克交易所股票代码：KPTI] 共同开展）针对复发/难治性血液及实体肿瘤的临床研究。希维奥® 已在韩国获批用于两个适应症的治疗：•  联合地塞米松用于治疗已接受至少四种既往治疗且对至少两种蛋白酶体抑制剂、两种免疫调节剂和一种抗CD38单克隆抗体药物难治的复发/难治性多发性骨髓瘤（R/R MM）成人患者。•  单药用于治疗既往接受过至少二线系统性治疗的复发/难治性弥漫性大B细胞淋巴瘤（R/R DLBCL）（非特指）成人患者，适应症包括由滤泡淋巴瘤转化的DLBCL。希维奥® 已在中国大陆地区获批用于一个适应症的治疗：•  联合地塞米松用于治疗既往接受过治疗且对至少一种蛋白酶体抑制剂，一种免疫调节剂以及一种抗CD38单克隆抗体药物难治的复发/难治性多发性骨髓瘤（R/R MM）成人患者。希维奥® 已在澳大利亚获批用于两个适应症的治疗：•  联合硼替佐米及地塞米松塞（XVd方案）用于治疗接受过至少一种既往治疗的多发性骨髓瘤（MM）成人患者。•  联合地塞米松（Xd方案）用于治疗接受过至少三种既往治疗且对至少一种蛋白酶体抑制剂（PI）、一种免疫调节药物（IMiD）和一种抗CD38单克隆抗体药物（mAb）难治的复发/难治性多发性骨髓瘤（R/R MM）成人患者。希维奥® 已在新加坡获批用于三个适应症的治疗：•   联合硼替佐米和地塞米松用于治疗接受过至少一种既往治疗的多发性骨髓瘤（MM）成人患者。•   联合地塞米松用于治疗接受过至少四种既往治疗且对至少两种蛋白酶体抑制剂、至少两种免疫调节剂及一种抗CD38单克隆抗体药物难治的复发/难治性多发性骨髓瘤（R/R MM）成人患者。•  单药用于治疗接受过至少二线系统性治疗且无法接受造血干细胞移植的复发/难治性弥漫性大B细胞淋巴瘤（R/R DLBCL）（非特指）成人患者，适应症包括由滤泡淋巴瘤转化的DLBCL。关于德琪医药德琪医药有限公司（简称“德琪医药”，香港交易所股票代码：6996.HK）是一家以研发为驱动，并已进入商业化阶段的生物制药领先企业，以“医者无疆，创新永续”为愿景，德琪医药专注于血液及实体肿瘤领域的同类首款和同类最优疗法的早期研发、临床研究、药物生产及商业化，致力于通过提供突破性疗法，改善全球患者生活质量。自2017年以来，德琪医药现已建立了一条不断延展的由15款临床及临床前产品构成的管线，其中，10款产品具有全球权益，5款产品具有包括大中华区在内的亚太权益。公司已在美国及多个亚太市场获得24个临床批件（IND），并递交了6个新药上市申请（NDA）。目前，希维奥®（塞利尼索片）已获得中国大陆、韩国、新加坡和澳大利亚的新药上市批准。关于百济神州百济神州是一家立足于科学的全球性生物科技公司，专注于开发创新、可负担的药物，旨在为全球患者改善治疗效果、提高药物可及性。目前公司广泛的药物组合包括40多款临床候选药物。公司通过加强自主研发能力和合作，加速推进多元、创新的药物管线开发。我们致力于在2030年前为全球20多亿人全面改善药物可及性。百济神州在全球五大洲打造了一支超过8,000人的团队。欲了解更多信息，请访问http://www.beigene.com.cn。参考文献：Armitage JO. The aggressive peripheral T-cell lymphomas: 2017. Am J Hematol. 2017 Jul;92(7):706-715