A Randomized Phase 1/2 Trial Evaluating the Addition of Tolinapant to Weekly Paclitaxel With or Without Bevacizumab in Patients With Recurrent Epithelial Ovarian Cancer

This phase I/II trial tests the safety, best dose and effectiveness of adding tolinapant (ASTX660) to paclitaxel with or without bevacizumab in treating patients with ovarian cancer that has come back after a period of improvement (recurrent). Tolinapant may stop the growth of tumor cells by blocking proteins, such as XIAP and cIAP1, that promote the growth of tumor cells and increase resistance to chemotherapy. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to the tumor. This may slow the growth and spread of tumor cells. Adding ASTX660 to paclitaxel with or without bevacizumab may be safe, tolerable and/or effective in treating patients with recurrent ovarian cancer.

开始日期2024-06-21

申办/合作机构

National Cancer Institute

ISRCTN11197711 / Recruiting临床1期

ASTFOX : A Phase I study of IAP antagonist, ASTX660 (tolinapant), in combination with standard of care FOLFOX chemotherapy in metastatic colorectal cancer

开始日期2024-04-30

申办/合作机构

NHS Greater Glasgow & Clyde

[+1]

NCT05912075 / Recruiting临床1期IIT

An Open-Label Multicenter Phase 1b Study of Tolinapant (ASTX660) in Combination With Radiotherapy/Chemoradiotherapy (RT/CRT) in Preoperative Treatment of Patients With Rectum Cancer (PRAAR 1: Preoperative Radiotherapy And ASTX660 in Rectum Cancer)

Compare two arms:
Chemotherapy followed by tolinapant (ASTX660) in combination with Long-Course Radio Chemotherapy (LCRT), and
Tolinapant (ASTX660) in combination with Short-Course Radiotherapy (SCRT) followed by chemotherapy For each patient, the treatment arm will be allocated on the following basis: patients will be allocated to the chemotherapy followed by LCRT arm unless they present at least one of the following criteria: contraindication to receive mFOLFIRINOX (including intolerance to irinotecan and UGT1A1*28 polymorphism), age > 75, general condition incompatible with the radiotherapy schedule of LCRT. In such case, patients will be allocated to the SCRT arm.
Tolinapant (ASTX660) will be administered orally once a day for 7 consecutive days every other week during 10 weeks (One week On / One week Off during 10 weeks).
Both treatment arms will have a dose escalation part to determine the MTD and/or RP2D, followed by an expansion part where up to 21 subjects will be dosed at the RP2D. Both arms will enroll simultaneously.

开始日期2023-12-19

申办/合作机构

Gustave Roussy, Cancer Campus, Grand Paris

100 项与 Tolinapant 相关的临床结果

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100 项与 Tolinapant 相关的转化医学

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100 项与 Tolinapant 相关的专利（医药）

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项与 Tolinapant 相关的文献（医药）

2022-04-01·Biochemical and biophysical research communications3区 · 生物学

Novel smac mimetic ASTX660 (Tolinapant) and TNF-α synergistically induce necroptosis in bladder cancer cells in vitro upon apoptosis inhibition

3区 · 生物学

Article

作者: Wang, Lei ; Hu, Changhua ; Zhao, Yu ; Hu, Xiaoquan

Apoptosis inhibition often leads to resistance to chemotherapeutics in bladder cancer (BC), resulting in poor prognosis of patients. Accumulating evidence suggests that induction of necroptosis, another type of programmed cell death, can be applied as an alternative strategy to kill apoptosis-insensitive BC cells. In this study, we showed that a novel Smac mimetic, ASTX660, also known as Tolinapant, can induce necroptosis in BC cells when apoptosis is inhibited. This is achieved by turning tumour necrosis factor (TNF)-α into a cytotoxic signal; ASTX660 then acts synergistically with TNF-α to induce necroptosis in BC cells. Mechanistic investigation showed that ASTX660 promoted the formation of the necrosome complex. Genetic or pharmacological inhibition of RIP1, RIP3, or MLKL, which are components of necrosome complex, provided protection against cell death induced by ASTX660 alone or ASTX660/TNF-α upon caspase inhibition. In addition, TNF-α/TNFR1 signalling and IRF1 are essential for the necroptosis induced by ASTX660 after the caspases are blocked. Our study highlights that ASTX660 can overcome the limitation of apoptosis induction via triggering necroptosis in BC cells. Therefore, our findings may provide some important clues for the design of a novel treatment strategy for BC.

2021-10-26·Blood advances2区 · 医学

Antagonism of inhibitors of apoptosis proteins reveals a novel, immune response-based therapeutic approach for T-cell lymphoma

2区 · 医学

Article

作者: Ferrari, Nicola ; Smyth, Tomoko ; Munck, Joanne ; Ferraldeschi, Roberta ; Lyons, John ; Keer, Harold ; Gewinner, Christina ; Saini, Harpreet ; Davis, Matthew P. ; Sims, Martin J. ; Jueliger, Simone ; Ward, George

Abstract:

Tolinapant (ASTX660) is a potent, nonpeptidomimetic antagonist of cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2) and X-linked IAP, which is currently being evaluated in a phase 2 study in T-cell lymphoma (TCL) patients. Tolinapant has demonstrated evidence of single-agent clinical activity in relapsed/refractory peripheral TCL and cutaneous TCL. To investigate the mechanism of action underlying the single-agent activity observed in the clinic, we have used a comprehensive translational approach integrating in vitro and in vivo models of TCL confirmed by data from human tumor biopsies. Here, we show that tolinapant acts as an efficacious immunomodulatory molecule capable of inducing complete tumor regression in a syngeneic model of TCL exclusively in the presence of an intact immune system. These findings were confirmed in samples from our ongoing clinical study showing that tolinapant treatment can induce changes in gene expression and cytokine profile consistent with immune modulation. Mechanistically, we show that tolinapant can activate both the adaptive and the innate arms of the immune system through the induction of immunogenic forms of cell death. In summary, we describe a novel role for IAP antagonists as immunomodulatory molecules capable of promoting a robust antitumor immune response in TCL.

2021-09-01·Molecular cancer therapeutics2区 · 医学

Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer

2区 · 医学

Article

作者: Longley, Daniel B. ; McDade, Simon S. ; Munck, Joanne M. ; Latimer, Cheryl ; Sessler, Tamas ; Lawler, Mark ; Crawford, Nyree ; Lees, Andrea ; McCann, Christopher ; Martins, Vanessa ; Kerr, Emma M. ; Coyle, Vicky M. ; Dunne, Philip D. ; Shah, Alpesh ; Smyth, Tomoko ; Fox, Jennifer P. ; McDaid, William ; Stott, Katie J.

Abstract:

Inhibitors of apoptosis proteins (IAPs) are intracellular proteins, with important roles in regulating cell death, inflammation, and immunity. Here, we examined the clinical and therapeutic relevance of IAPs in colorectal cancer. We found that elevated expression of cIAP1 and cIAP2 (but not XIAP) significantly correlated with poor prognosis in patients with microsatellite stable (MSS) stage III colorectal cancer treated with 5-fluorouracil (5FU)–based adjuvant chemotherapy, suggesting their involvement in promoting chemoresistance. A novel IAP antagonist tolinapant (ASTX660) potently and rapidly downregulated cIAP1 in colorectal cancer models, demonstrating its robust on-target efficacy. In cells co-cultured with TNFα to mimic an inflammatory tumor microenvironment, tolinapant induced caspase-8–dependent apoptosis in colorectal cancer cell line models; however, the extent of apoptosis was limited because of inhibition by the caspase-8 paralogs FLIP and, unexpectedly, caspase-10. Importantly, tolinapant-induced apoptosis was augmented by FOLFOX in human colorectal cancer and murine organoid models in vitro and in vivo, due (at least in part) to FOLFOX-induced downregulation of class I histone deacetylases (HDAC), leading to acetylation of the FLIP-binding partner Ku70 and downregulation of FLIP. Moreover, the effects of FOLFOX could be phenocopied using the clinically relevant class I HDAC inhibitor, entinostat, which also induced acetylation of Ku70 and FLIP downregulation. Further analyses revealed that caspase-8 knockout RIPK3-positive colorectal cancer models were sensitive to tolinapant-induced necroptosis, an effect that could be exploited in caspase-8–proficient models using the clinically relevant caspase inhibitor emricasan. Our study provides evidence for immediate clinical exploration of tolinapant in combination with FOLFOX in poor prognosis MSS colorectal cancer with elevated cIAP1/2 expression.

项与 Tolinapant 相关的新闻（医药）

2023-07-05

·药融圈

一文知悉：亚洲TOP制药企业，大冢集团

▲8月03-04日 CMC-China大会 · 限时免费扫码报名中注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。说起日本制药业界的大手企业，那一定有武田药品、大冢制药、Astellas制药、第一三共等。其中，以药品为主要业务的大冢集团（Otsuka Holdings Co.）更是涉及多个领域业务，还包括保健品、食品、化工以及器械等。如今已经有百年历史的大冢集团在全球的集团公司总数多达196个，研发基地和生产基地遍布全球，其中，研发基地42个（日本24个，海外18个），生产基地173个（日本51个，海外122个），员工人数更是达到47000+人。图：集团公司全球分布（数据截至2022年12月31日）核心运营公司大冢集团核心运营公司一共有七家，分别是大冢制药株式会社、大冢制药厂、大鹏制药有限公司、大冢仓库株式会社、大冢化学工业株式会社、大冢食品株式会社和大冢医疗器械株式会社。图：大冢集团核心运营公司大冢制药株式会社成立于1964年，主要业务为药品、临床检测设备、医疗器械设备、食品、化妆品及其他相关产品的制造、分销、进出口；大冢制药厂最初成立于1921年，当时名为大冢精药（大冢制药），是大冢集团成长起来的原始公司；大鹏制药有限公司成立于1963年，是一家研发驱动的专业制药公司，专注于肿瘤学、过敏和免疫学以及泌尿科领域；大冢仓库株式会社成立于1961年，其核心业务一直以提供药品和食品的物流服务为中心，为大冢集团在药品、食品和饮料、日用品三个产品领域搭建了一个共同的分销平台。近年来，该公司已发展到在集团外部提供物流服务；大冢化学工业株式会社成立于1950年，向社会提供满足广泛需求的材料和产品，旨在成为一家在化学业务中为改善生活和改善地球环境做出贡献的公司；大冢食品株式会社成立于1955年，主要业务是食品和饮料的制造、销售、进口和销售；大冢医疗器械株式会社成立于2011年，主要为大冢集团旗下公司研发、制造和销售医疗器械所有相关业务，还包括医疗器械运营管理等。业务布局从1921年至今，大冢集团已经有102年的历史，在这百年岁月中，大冢不断扩展集团业务，从药品到医疗保健品，再到消费品以及化工业务，大冢集团一直在打破思维的局限，不断为消费者带来新的产品，其成长不仅是自身多元化业务组合支撑增长的过程，更是不断为病患以及健康人群带来新的希望以及便利的过程。以下是大冢自成立以来业务发展情况。■保健品及其他 ■药品，包括静脉注射液图：大冢业务发展情况基于全面卫生保健的概念，大冢集团一直通过其业务维持并促进健康，以及诊断和治疗疾病。为了展示作为一家医疗保健公司的真正价值，大冢集团利用新技术为民众提供更加健康的机会，从食品到保健品，再到药品，大冢集团一直在追求可持续增长。大冢集团公司众多，主要具备七个核心经营公司，从业务布局来看集团主要分为四大业务板块，分别是药品、营养保健品、消费品和其他业务（其他业务主要为化学药品、精细化学品、仓储和配送、包装以及电子设备等）。01制药业务药融圈旗下，药融云数据www.pharnexcloud.com显示：大冢集团以解决未满足的医疗需求为主题，把精神病学、神经病学和肿瘤学领域作为优先研究的领域。此外，还从事心血管和肾脏系统、消化系统、眼科、诊断、静脉注射液和医疗设备等广泛的其他领域和业务，提供从诊断到治疗的全面医疗保健服务。1、业务领域（1）精神病学和神经病学（CNS）精神分裂症、双相情感障碍和重度抑郁症等精神疾病可以在任何年龄发展，并影响一个人的社会生活、职业和学习，此外，随着世界人口老龄化，人们越来越担心阿尔茨海默症发病率的增加，这些疾病不仅影响患者的生活质量，还会给家庭成员、护理人员以及医疗保健经济带来压力。目前由于许多精神和神经系统疾病的原因和机制尚未完全了解，使得该领域新药的发现极其困难，所以目前仍有许多这类疾病尚未建立成熟的治疗方法。大冢集团于1970年代进入精神病学和神经病学领域，并以促进医疗需求为目标，接受着发现新药的挑战。该集团通过应用小分子和大分子化合物技术以及数字技术，开发广泛且具有高潜力的产品线和产品阵容，其目标是成为精神病学和神经病学领域的全球顶级企业。中枢神经系统类药物主要有REXULTI / RXULTI（brexpiprazole）、ABILIFY Maintena、ABILIFY（Aripiprazole）、NUEDEXTA（dextromethorphan hydrobromide and quinidine sulfate）、Neupro Patches（Rotigotine）、Selincro（Nalmefene）和AJOVY（fremanezumab）。图：中枢神经系统药物REXULTI / RXULTI用于治疗精神分裂症，目前由大冢和Lundbeck共同开发和销售。2018年在日本推出，在全球约60个国家销售；在美国，它还作为重度抑郁症的辅助治疗药物在市场上销售。ABILIFY是一种抗精神病药物，2006年在日本推出用于治疗精神分裂症，并于2012年获得了改善躁狂症状或双相情感障碍的额外适应症。Abilify Maintain是一种肌内注射用缓释水性混悬剂，是抗精神病药物ABILIFY（Aripiprazole）的长效制剂。2013年在美国上市用于治疗精神分裂症，随后在50多个国家上市。2017年，该产品在美国和加拿大被批准用于治疗双相I型障碍。2015年在日本上市用于治疗精神分裂症，并于2020年被批准用于双相I型障碍的附加适应症。Nuedexta是世界上第一个也是唯一一个被批准用于治疗假性延髓病（PBA）的药物。它是由作用于中枢神经系统的氢溴酸右美沙芬和抑制代谢的硫酸奎尼丁联合使用，以提高右美沙芬的有效血药浓度。由美国子公司Avanir Pharmaceuticals销售。Neupro是世界上唯一一种每日一次的透皮多巴胺受体激动剂。2002年，Otsuka从比利时UCB公司获得了在日本的开发和销售权。从2013年开始在日本上市。Selincro是日本第一个双重作用的阿片系统调节剂。2013年，大冢与Lundbeck就Lundbeck的Selinclo在日本的开发和商业化达成了协议，于2019年由大冢推出。Ajovy由Teva Pharmaceutical Industries拥有，是一种皮下注射的抗CGRP（降钙素基因相关肽）单克隆抗体，通过重组DNA技术生产。2017年，大冢获得了在日本的开发和销售权，并于2021年开始销售。（注：CGRP被认为在偏头痛发作中起重要作用。Ajovy靶向CGRP配体，抑制其与CGRP受体的结合。）（2）肿瘤学大鹏制药不仅拥有广泛的产品组合，还有其专有的药物发现平台技术提供支持，包括独特的专有生化调节技术，以及半胱氨酸米克斯药物发现技术，实现治疗靶点的特定共价修饰，以及由Astex Pharmaceuticals建立的基于片段的药物发现技术。此外，它还通过企业风险投资寻找与有前途的初创公司合作的机会，从而扩大其在癌症免疫治疗等领域的开发渠道，并获得创新的药物发现平台技术。同时，大冢制药以外部合作为中心，正在接受开发新疗法的挑战，这包括在基因修饰的T细胞疗法等领域与新模式产生协同效应。各个集团公司正在结合其优势领域积累的资产，以支持全球运营并提高业务价值。图：肿瘤学药物由ARIAD（2017年被武田收购）发现的ICLUSIG（Ponatinib）是一种口服酪氨酸激酶抑制剂，2016年在日本推出。Busulfex（Busulfan Injection）是血癌骨髓移植前的一种调节剂。它已被全球接受为支持医学移植的标准治疗方法。（3）心血管和肾脏系统在心血管和肾脏领域，除了加强其专有的药物发现平台外，大冢集团还计划积极进行增长投资，其中包括与Aurinia Pharmaceuticals的业务联盟以及收购Visterra（Visterra是一家拥有肾脏疾病相关产品线的公司）。同时大冢集团结合在制药和医疗设备技术方面的专业知识，还开发了微创且对身体影响较小的医疗设备。2021年，大冢在日本推出了血管支架系统。同时，其超声肾去神经支配系统是一种革命性的治疗方法，适用于现有治疗无效的高血压患者，被美国FDA授予突破性设备称号。图：心血管和肾脏疾病产品Samsca / JINARC / JYNARQUE（Tolvaptan）于2010年在日本被批准用于治疗心力衰竭（液体积聚）引起的水肿，并于2013年被批准用于治疗肝硬化患者的水肿。2014年，Samsca在日本被批准为世界上首个治疗常染色体显性多囊肾病（ADPKD）的药物，并在包括北美和欧盟成员国在内的地区获得了其他批准。目前，Samsca/JINARC/JYNARQUE在40多个国家被批准用于多种适应症。Samtasu是口服托伐普坦（通用名为托伐普坦磷酸钠）的前体药物，在日本于2022年被批准用于治疗心力衰竭（液体积聚）引起的水肿。（注：前药是一种给药后在人体内转化为活性药物的药物。）Pletaal（Cilostazol）可抑制血小板聚集并具有外周血管舒张的作用。1988年在日本上市，用于治疗与慢性动脉阻塞相关的症状，并于2003年被批准用于预防复发性脑梗死。2010年，Pletaal OD片剂在日本上市。2、研发基地大冢集团在全球建立了研发基地网络，为创新产品的研发建立了一个全球结构，以帮助治疗疾病和支持日常健康，制药业务的研发基地主要位于日本、欧洲、美洲和亚太地区。其中在中国有：大冢（上海）药物研究开发有限公司等。图：制药业务主要研发基地分布图02营养保健品大冢集团目前一共有三个营养保健品业务研究机构，分别是Saga营养保健品研究所（自1984年作为日本第一家临床运动和营养私人研究机构成立以来，该研究所在与运动和营养，女性健康和其他健康问题相关的各个领域进行了研发）、Otsu营养保健品研究所（Otsu营养保健品研究所成立于2000年，旨在推进肠道免疫的研究，特别关注肠道，肠道在整体健康中起着关键作用）和医疗食品研究所（研究领域多种多样，包括营养不良、营养病理、脱水和喂养功能），大冢的研究机构利用制药业务中获得的专业知识，根据科学证据开发原创营养保健品，其营养保健品业务主要专注于有助于维持和改善日常健康的功能性饮料和食品。营养保健品研发基地主要坐落于日本，其主要研发基地分布图如下所示：图：营养保健品主要研发基地分布03消费品大冢集团的消费品业务主要是大冢食品株式会社，该公司主要从事食品和饮料领域的研发。1968年，大冢食品发布了世界上第一款塑料袋（蒸煮袋）的商用食品Bon Curry，此后推出了一系列走在时代前面的产品，例如Mannan Hikari（一种由精制魔芋粉和其他成分制成的米类加工食品）、My Size系列（适合那些觉得饭菜的份量和卡路里数高的人）和Zero Meat（一种由大豆制成的无肉产品）。大冢食品结合风味、安全、安心和健康的四个关键成分，旨在开发人们乐于为朋友和家人提供的各种产品。基于其原创的概念和开发能力，以及传统的开拓精神，大冢食品将继续为人们的餐桌提供原创风味和新梦想。图：大冢食品大冢食品主要研发基地分布于中国上海和日本。图：大冢食品主要研发基地分布图04其他业务大冢始终致力于创造最先进的技术，满足每个业务领域的客户需求，公司根据其战略开发支持日常生活的产品。大冢集团的其他业务以大冢化学株式会社和大冢电子株式会社为中心，包括供应汽车、电气和电子设备以及建筑材料领域的各种材料的化学业务；以环保物流为目标的运输和仓储业务（主要面向大冢集团的药品、食品和饮料）；以及支持尖端技术开发的电子设备业务。大冢化学通过创造核心技术，通过可持续发展为社会做出贡献的研究和开发。中央研发实验室处理研发的不同方面，主要包括从中间实验设施的基础研究和原型测试到应用程序的开发；综合研究实验室从先进有机材料和先进无机材料领域的许多不同角度进行研究和开发，采取开箱即用的方法进行研究和开发；先进聚合物实验室使用大冢独创的受控自由基聚合技术TERP方法进行功能聚合物的研究和开发；功能复合材料实验室研究和开发具有滑动、精密增强、导电、介电等性能的复合材料。大冢电子以光为媒介的技术为基础，分为三类业务，这三类是医学测试设备，分析设备和光谱仪。在医学测试领域，大冢的医学测试设备包括POConePlus，这是一种测试幽门螺杆菌的临床试验设备。在分析领域，分析设备包括Zeta电位和纳米粒径测量仪器。在光谱领域，大冢的光谱仪包括用于半导体、功能材料和薄膜材料行业的非接触式测厚仪等检测仪器。主要研发基地为中国和日本。图：其他业务主要研发基地分布图近期研发活动/R&D01制药业务大冢集团主要专注于精神病学、神经病学和肿瘤学领域的研究和开发，亦专注于心血管及肾脏系统等尚未完全解决的领域进行研发。截至2023年3月31日的三个月期间，医药业务的研发活动部分总结如下。表：近期研发活动（1）精神病学和神经学①研发代码为OPC-34712的药物REXULTI / RXULTI（brexpiprazole）2023年1月份在日本申请针对重度抑郁症的研究；2023年1月份在美国申请针对与阿尔茨海默氏症痴呆相关的躁动的研究；在欧洲针对其对重度抑郁症和与阿尔茨海默氏症痴呆相关的躁动的研究因业务原因已停产。②研发代码为AVP-786的药物deuterium-modified dextromethorphan, quinidine在美国针对精神分裂症的阴性症状的研究因战略原因已停产。（2）肿瘤学①研发代码为ASTX660+ASTX727的药物tolinapant+decitabine, cedazuridine用于治疗T细胞淋巴瘤的研究已于2023年2月份在美国开始第一阶段试验；②研发代码为AP24534的药物ICLUSIG（ponatinib）用于治疗慢性粒细胞白血病、急性淋巴细胞白血病的研究已于2023年3月在中国提出申请；③研发代码为AB122 + TAS-120的药物imberelimab +futibatinib用于治疗实体瘤的研究已于2023年1月在日本开始第一阶段试验；④在日本研发代码为OPB-171775的研究因战略原因已停产。（3）心血管和肾脏系统①研发代码为ETC-1002的药物bempedoic acid用于治疗高胆固醇血症的研究已于2023年2月在日本开始第三期临床试验）；②研发代码为OPC-131461的主要针对心脏水肿的研究已于2023年1月在日本开始二期临床试验。（4）其他类别①研发代码为OPA-15406的药物difamilast针对特应性皮炎的研究已于2023年2月开始在中国开展第三期临床试验；②研发代码为OPC-1085EL的药物carteolol, latanoprost针对青光眼的研究已经在中国开始第三期临床试验；③研发代码为VIS171针对自身免疫性疾病的研究已于2023年1月开始第一阶段试验。4研发代码为OPS-2071，在日本、美国都进入了临床2期阶段；药融圈旗下，药融云数据www.pharnexcloud.com显示：本品已经启动在中国的2期临床试验，用于治疗腹泻型-肠易激综合征（IBS-D）。据悉，本品为大冢上海开发的小分子新药。药融云数据，www.pharnexcloud.com02营养保健在营养保健品业务方面，集团利用其在制药业务方面的知识，进行基于科学的原创产品的研究和开发，以维护和促进人们的健康。SOYJOY品牌的大豆零食棒提供了一种方便的方式来食用全大豆的营养，SOYJOY水果和奶酪于2023年3月推出。此外，在化妆品领域，作为男性护肤品牌UL·OS的一部分，大冢利用独特的理念和技术专注于健康的皮肤，于2023年3月推出了UL·OS头皮洗发水Volume-up，主要适用于关注头发质地和弹性的男性。03消费品在消费品业务方面，大冢集团以蒸煮食品、饮料、植物性食品为目标，以食品与健康为主题，创造和提出创新产品，旨在解决与变化中的社会相关的各种问题，例如涉及健康、环境、人口和老龄化社会的问题。截至2023年3月31日的三个月，消费品业务的研发费用为1.62亿日元。04其他在其他业务方面，本集团主要从事特种化学品及精细化学品的研发。本集团专注于有机和无机合成技术，并围绕自主技术和下一代领域进行新产品的研发。截至2023年3月31日的三个月期间，其他业务的研发费用为13.83亿日元。财政营收大冢集团2022年收入为17380亿日元（约合120.37亿美元），同比上一年增长了16.0%，业务利润为1749亿日元，比上一年增长了11.3%，而这部分收入主要归功于四大全球产品（ABILIFY Maintena、REXULTI/RXULTI、Samsca / JINARC / JYNARQUE和LONSURF）和营养保健品的增长，据统计，制药业务中四大全球产品的销售额同比增长了26.4%，营养保健品业务的功能性饮料和营养补充剂贡献巨大，同比增长了16.0%。表：2022财年收入统计截至2023年3月31日的三个月，集团总收入为4483.44亿日元（约合31.05亿美元），比上一财年同期增长17.9%，所有业务的收入均有所增长。主要是由于四种全球产品的销售额增长以及许可产品的特许权使用费增长，推动了制药业务的业绩。此外，在营养保健品业务中，随着健康意识的提高，POCARI SWEAT和Nature Made的销售额继续增长。研发费用为679.68亿日元，与上年同期相比增长了14.5%，主要是由于正在开发的用于治疗注意力缺陷多动障碍（ADHD）的centanafadine和正在开发的用于治疗非小细胞肺癌的zipalertinib/TAS6417的开发费用增加。扣除研发费用的营业利润为1416.49亿日元，比上一年同期增长39.1%。而SG&A费用比率随着对销售，一般和管理费用的适当控制而改善，由于销售增长超过预期，并对销售、一般和管理费用实施了适当的控制，企业利润大幅增长至736.81亿日元，与上年同期相比增长了73.5%。表：2023年第一季度财政营收从四大业务版块来看，2023年第一季度制药业务销售额为3031.61亿日元，与上一年同期相比增长20.3%；医疗保健业务收入为1039.72亿日元，与上一年同期相比增长15.1%；消费品业务收入为82.33亿日元，与上一年同期相比增长了7.3%；由于价格调整，特殊化学品业务的销售额略有增长，精细化工业务的销售额增长主要是由于抗生素中间体的销售额增加；在运输和仓储业务方面，集团通过协调物流数据和增加处理量来加强整体医疗保健配送平台，从而吸引了新的外部客户，销售额增加。作为全球市场的一位重要参与者，大冢不管是从集团公司分布还是业务版块的布局上来看都在追求全球化，从收入来看，经过百年沉淀的大冢目前是日本TOP5的制药商，那么未来的大冢又会继续登上哪座高峰呢......近期资讯2023年4月28日，FDA批准大冢和Lundbeck的Abilify Asimtufii（阿立哌唑）用于治疗精神分裂症或成人双相I型障碍的维持单药治疗。2023年5月11日，大冢和Lundbeck宣布FDA批准Rexulti的补充新药申请（SNDA），用于治疗与阿尔茨海默病引起的痴呆相关的躁动。这一批准使Rexulti成为美国批准的第一种也是唯一一种治疗与阿尔茨海默病相关的躁动的药物。图：相关新闻此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场参考：NMPA/CDE；药融云数据，www.pharnexcloud.com；FDA/EMA/PMDA；相关公司公开披露（除标注外，正文图片均来自企业官方）；https://www.otsuka.com/en/；https://www.otsuka.co.jp/en/；https://www.otsukakj.jp/en/；https://www.otsukafoods.co.jp/；等等。关于CMC-China 博览会融合产业力量，重构行业未来！本次CMC-China博览会汇聚300+医药及上下游全产业链的企业积极报名参展，数千名专业观众报名参观，展会现场将举办15场专业论坛。充分体现了“医药人办医药展，专业人办专业展”的理念。了解更多：数据看展会丨一文看懂第五届CMC-China制药博览会观众亮点点分享点点赞点在看

医药出海

2023-03-09

·Business Wire

Cutaneous T-Cell Lymphoma - Pipeline Insight, 2022 - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "Cutaneous T-Cell Lymphoma - Pipeline Insight, 2022" clinical trials has been added to ResearchAndMarkets.com's offering. This "Cutaneous T-Cell Lymphoma - Pipeline Insight, 2022" report provides comprehensive insights about 25+ companies and 27+ pipeline drugs in Cutaneous T-Cell Lymphoma pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. Geography Covered Global coverage Cutaneous T-Cell Lymphoma Understanding Cutaneous T-Cell Lymphoma: Overview Cutaneous T-cell lymphoma (CTCL) is a rare type of blood cancer. It begins in a type of white blood cell called the T-lymphocyte (T-cell). T-cells help prevent infections and other diseases. As odd as it sounds, most T-cells are found in our skin. That's because our skin is the first line of defense against disease. The surface of an adult's skin contains about 20 billion T-cells. That's nearly twice as many T-cells as found in other parts of the body. There are many types of CTCL. More than half the people who develop CTCL will have one of the following types: Mycosis fungoides or Sezary syndrome. Mycosis fungoides is the most common type of CTCL. This type tends to worsen very slowly. It can stay in its earliest stage, which often looks like rash, for years. In this stage, the cancer is often difficult to diagnose because it tends to looks like eczema or psoriasis. These conditions are much more common than CTCL. Sezary syndrome is more aggressive. It can also look like eczema. Some people develop red and swollen skin over much of their body. Their skin may feel hot, sore, and extremely itchy. Because CTCL is rare and often looks like eczema or another common skin disease, it can take time to get the diagnosis. Some people who have CTCL are referred to a dermatologist because it's thought that they have a stubborn case of eczema or psoriasis. This report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Cutaneous T-Cell Lymphoma pipeline landscape is provided which includes the disease overview and Cutaneous T-Cell Lymphoma treatment guidelines. The assessment part of the report embraces, in depth Cutaneous T-Cell Lymphoma commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Cutaneous T-Cell Lymphoma collaborations, licensing, mergers and acquisition, funding, designations and other product related details. Cutaneous T-Cell Lymphoma Emerging Drugs Chapters This segment of the Cutaneous T-Cell Lymphoma report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Cutaneous T-Cell Lymphoma Emerging Drugs SGX301: Soligenix SGX301 is a novel first-in-class photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a potent photosensitizer that is topically applied to skin lesions, is taken up by the malignant T-cells, and then activated by fluorescent light 16 to 24 hours later. HyBryte (synthetic hypericin or SGX301) may provide a safer, more convenient alternative. It is a topical ointment which is applied to the lesions and then activated by safe visible fluorescent light. HyBryte is being tested as a photodynamic light therapy with an enhanced safety profile and a treatment regimen that may be completed in as little as 6 weeks. Its pivotal Phase III clinical study (the "FLASH" study) for CTCL has completed enrollment showing a statistically significant outcome after 6 weeks treatment (p=0.04) with continued improvement to 40% response rate after 12 weeks treatment (p< 0.0001). Lacutamab : Innate Pharma Lacutamab (IPH4102) is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody, which is currently in clinical trials for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease. This group of rare cutaneous lymphomas of T lymphocytes has a poor prognosis with few efficacious and safe therapeutic options at advanced stages. KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up to 90% of patients with certain aggressive CTCL subtypes, in particular, Sezary syndrome. It is currently being evaluated in Phase II stage of development. BNZ-1: Bioniz BNZ-1 is a selective inhibitor of three members of the IL-2 family: IL-2, IL-9, and IL-15. The profile of BNZ-1 is promising as a long-term therapy capable of transforming the standard of care in CTCL as data implicates the dysregulation of IL-2/IL-9/IL-15 as responsible for disease pathology. Bioniz conducted a Phase I/II study in CTCL, in which BNZ-1 exhibited a substantial improvement in safety and efficacy relative to standard of care. BNZ-1 has orphan drug designation in US and EU. In February 2022, Equillium, Inc. announced that it has acquired Bioniz Therapeutics, Inc., a privately held clinical-stage biotechnology company. Bioniz developed its novel structured-domain peptides, including BNZ-1 and BNZ-2, entirely in-house from its proprietary product discovery platform. BNZ-1 is Phase II/III ready in CTCL with open U.S. INDs for each indication and has orphan designation for CTCL in the U.S. and Europe. Cutaneous T-Cell Lymphoma: Therapeutic Assessment This segment of the report provides insights about the different Cutaneous T-Cell Lymphoma drugs segregated based on following parameters that define the scope of the report, such as: Major Players in Cutaneous T-Cell Lymphoma There are approx. 25+ key companies which are developing the therapies for Cutaneous T-Cell Lymphoma. The companies which have their Cutaneous T-Cell Lymphoma drug candidates in the most advanced stage, i.e. Phase III include, Soligenix Phases The report covers around 27+ products under different phases of clinical development like Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Cutaneous T-Cell Lymphoma pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as Intra-articular Intraocular Intrathecal Intravenous Ophthalmic Oral Parenteral Subcutaneous Topical Transdermal Molecule Type Products have been categorized under various Molecule types such as Oligonucleotide Peptide Small molecule Product Type Drugs have been categorized under various product types like Mono, Combination and Mono/Combination. Cutaneous T-Cell Lymphoma: Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Cutaneous T-Cell Lymphoma therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Cutaneous T-Cell Lymphoma drugs. Cutaneous T-Cell Lymphoma Report Insights Cutaneous T-Cell Lymphoma Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs Cutaneous T-Cell Lymphoma Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players Soligenix Elorac Innate Pharma Viridian Therapeutics Sorrento Therapeutics Bio-Path Holdings Legend Biotech Genzada Pharmaceuticals VidacPharma Bioniz Therapeutics Otsuka Pharmaceutical Hoffmann-La Roche BioInvent International AB Scopus BioPharma Codiak BioSciences Merck Sharp & Dohme LLC Otsuka Pharmaceutical Co., Ltd. Myeloid Therapeutics Jiangsu Simcere Pharmaceutical miRagen Therapeutics Kymera Therapeutics Citius Pharmaceuticals 4SC Equillium Key Products SGX301 BNZ-1 Lacutamab ExoIL-12 BP1002 MRG-106 BBI-3000 WP1220 Tucidinostat IPH4102 Resiquimod VDA-1102 Resminostat Pembrolizumab ASTX660 KT-333 MT-101 SIM1811-03 Cobomarsen LB1901 EQ101 For more information about this clinical trials report visit https://www.researchandmarkets.com/r/uspzvl About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

临床2期孤儿药临床3期

2021-05-06

·GlobeNewswire

T-cell Leukemia Pipeline: Comprehensive Analysis of 15+ Key

Los Angeles, USA, May 05, 2021 (GLOBE NEWSWIRE) -- T-cell Leukemia Pipeline: Comprehensive Analysis of 15+ Key Players and 15+ Key Therapies Out of all T-cell Leukemia pipeline therapies, HBI-8000 is set to capture the maximum patient pool owing to its immunomodulatory function. DelveInsight’s ‘T-cell Leukemia Pipeline Insights’ report provides a holistic view of the pipeline therapies that are under development in pre-clinical as well as clinical stages of development, and growth prospects across the T-cell Leukemia domain. Some of the key highlights of the T-cell Leukemia Pipeline report: Got queries? Want to know more? Request for Sample @ T-cell Leukemia Emerging Therapies and Forecast The report lays down a complete coverage of the therapeutics by development stage, product type, and route of administration, molecule type, and MOA type for T-cell Leukemia across the complete product development cycle, including all clinical and non-clinical stages. The T-cell Leukemia pipeline report puts on the table business opportunities, threats, prospective collaborations, strong competitors, growth strategies, and failed as well as discontinued drugs. T-cell Leukemia Pipeline Drugs Request for Sample to know more @ T-cell Leukemia Pipeline Analysis, Key Companies and Futuristic Trends T-cell Leukemia Therapeutic Assessment The T-cell Leukemia Pipeline report proffers exhaustive insights into active pipeline assets segmented by Stage, Product Type, Route of Administration, Molecule Type, Target, and Indications of various drugs. By Product Type By Stage By Molecule Type By Route of Administration By Mechanism of Action By Targets Get in touch with our Business executive for Rich and Deep Market Assessment and Consulting Solutions Scope of the Report Coverage: GlobalKey Players: Daiichi Sankyo; Bioniz; Otsuka Pharmaceutical; Seagen /Takeda; HUYA Bioscience; iCell Gene Therapeutics; Gracell Biotechnology; Ascentage Pharma Group; Celgene Corporation; Shorla Pharma; AVM Biotechnology; Expression Therapeutics; miRagen Therapeutics, and others.Key T-cell Leukemia Pipeline Therapies: Valemetostat; BNZ-1; ASTX 660; Brentuximab vedotin; HBI-8000; CD4CAR; CD7 UCAR-T cells; APG-115; Romidepsin; SH-111; Cobomarsen; AVM-0703, and others. Reach out @ T-cell Leukemia Pipeline: Novel therapies and emerging technologies Table of Contents Visit to know more of what’s covered @ T-cell Leukemia Emerging Therapies Browse through Related Reports CAR T-Cell Therapy for Acute Lymphoblastic LeukemiaDelveInsight’s “CAR T-Cell Therapy for Acute Lymphoblastic Leukemia (ALL)- Market Insights and Market Forecast- 2030” report. CAR T-Cell Therapy for Acute Lymphoblastic Leukemia Pipeline DelveInsight’s, “CAR T-Cell Therapy for Acute Lymphoblastic Leukemia - Pipeline Insight, 2021,” report provides comprehensive insights about 5+ companies and 5+ pipeline drugs in CAR T-Cell Therapy for Acute Lymphoblastic Leukemia pipeline landscape. Adult T Cell Leukemia Lymphoma MarketDelveInsight's "Adult T-Cell Leukemia-Lymphoma - Market Insights, Epidemiology, and Market Forecast-2030" report. Acute Myeloid Leukemia MarketDelveInsight's "Acute Myeloid Leukemia (AML) Market Insights, Epidemiology, and Market Forecast-2030" report. B-Cell Chronic Lymphocytic Leukemia MarketDelveInsight's "B-Cell Chronic Lymphocytic Leukemia - Market Insights, Epidemiology, and Market Forecast-2030" report. Hairy Cell Leukemia Market Insight Epidemiology and Market ForecastDelveInsight's 'Hairy Cell Leukemia (HCL)- Market Insights, Epidemiology and Market Forecast-2028' report. Bowens Disease MarketDelveInsight's "Bowen's Disease - Market Insights, Epidemiology, and Market Forecast-2030" report. Buergers Disease MarketDelveInsight's "Buerger’s Disease - Market Insights, Epidemiology, and Market Forecast-2030" report. Brucellosis MarketDelveInsight's "Brucellosis - Market Insights, Epidemiology, and Market Forecast-2030" report. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing end-to-end comprehensive solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve. For more insights, visit Pharma, Healthcare, and Biotech News

细胞疗法合作

100 项与 Tolinapant 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16160

研发状态

适应症	最高研发状态	国家/地区	公司
外周T细胞淋巴瘤	临床2期	波兰更多	Astex Pharmaceuticals, Inc. 更多
晚期恶性实体瘤	临床2期	美国更多	Astex Therapeutics Ltd. 更多
复发性T细胞淋巴瘤	临床2期	美国更多	Astex Pharmaceuticals, Inc. 更多
实体瘤	无进展	比利时更多	Astex Pharmaceuticals, Inc. 更多
淋巴瘤	无进展	比利时更多	Astex Pharmaceuticals, Inc. 更多

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02503423 (ASCO2022)	临床2期	T细胞淋巴瘤	230	Tolinapant	築積淵衊鑰範鑰構膚選(築觸獵築鹽襯糧繭壓築) = 範願齋鬱鏇壓糧簾膚鑰選衊襯窪願窪淵鏇廠餘 (鏇餘淵獵鑰鬱鬱鑰廠積, 1)	-	2022-06-02
NCT02503423 (EHA2022) 人工标引	临床2期	外周T细胞淋巴瘤 \| 皮肤T细胞淋巴瘤	149	tolinapant 180 mg (PTCL)	觸憲鏇鑰網鏇範廠積夢(蓋觸遞餘選觸築艱願齋) = 顧製繭網築繭夢築齋艱襯選淵選夢衊蓋鬱構廠 (廠鹽觸膚網範艱選願製 ) 更多	积极	2022-05-12
NCT02503423 (EHA2022) 人工标引	临床2期	外周T细胞淋巴瘤 \| 皮肤T细胞淋巴瘤	149	tolinapant 180 mg (CTCL)	觸憲鏇鑰網鏇範廠積夢(蓋觸遞餘選觸築艱願齋) = 艱鹹鹽窪廠範艱鏇淵製襯選淵選夢衊蓋鬱構廠 (廠鹽觸膚網範艱選願製 ) 更多	积极	2022-05-12
NCT02503423 (EHA2022)	临床2期	T细胞淋巴瘤	230	Azacytidine	製觸憲觸蓋憲蓋網製選(積簾積齋衊遞繭夢淵製) = 範製憲壓網顧選鏇廠衊鬱鏇願獵衊獵襯簾網築 (鑰願鑰襯遞遞醖淵願選 )	-	2022-05-12
NCT02503423 (EHA2022)	临床2期	T细胞淋巴瘤	230	Decitabine	製觸憲觸蓋憲蓋網製選(積簾積齋衊遞繭夢淵製) = 製淵蓋願鏇選製觸鹽願鬱鏇願獵衊獵襯簾網築 (鑰願鑰襯遞遞醖淵願選 )	-	2022-05-12
NCT02503423 (Pubmed \| Clin Cancer Res) 人工标引	临床1期	肿瘤 \| 淋巴瘤	45	ASTX660	衊簾範選鹽餘鹽網艱製(壓淵齋積壓鏇齋蓋蓋顧) = 3 pts at 270 mg/day and 1 pt at 210 mg/day 範衊繭鑰製襯構蓋觸廠 (遞構遞遞獵顧遞顧鑰鬱 ) 更多	积极	2020-06-15
NCT02503423 (AACR2019) 人工标引	临床2期	实体瘤 \| 淋巴瘤	107	ASTX660	蓋壓艱顧夢膚製範網餘(繭醖遞齋鹹膚膚鑰壓鬱) = 鏇鑰範艱願蓋鏇繭範鹹衊夢獵顧淵鏇廠鬱遞鏇 (網製繭窪淵憲衊膚選鏇 ) 更多	积极	2019-12-01
NCT02503423 (EHA2019)	临床1/2期	外周T细胞淋巴瘤 \| 皮肤T细胞淋巴瘤	230	ASTX660 180mg/day	鏇製築鑰窪糧襯艱繭顧(醖醖膚築顧醖壓壓繭願) = 窪獵鑰窪窪糧築鬱簾膚蓋鏇餘壓築鹹簾鹹壓襯 (廠選蓋網襯蓋築壓齋築 )	-	2019-06-15