高三尖杉酯碱(Omacetaxine Mepesuccinate) - 在研适应症：骨髓增生异常综合征，费城染色体阳性慢性粒细胞白血病，真性红细胞增多症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

(2'R,3S,4S,5R)-(−)-homoharringtonine、(−)-homoharringtonine、HHT

+ [22]

靶点-

作用机制

蛋白质生物合成抑制剂

治疗领域

肿瘤血液及淋巴系统疾病其他疾病+ [2]

在研适应症

骨髓增生异常综合征费城染色体阳性慢性粒细胞白血病真性红细胞增多症+ [8]

非在研适应症

急性红细胞白血病急性巨核细胞白血病伴有 11q23 异常的急性髓系白血病+ [8]

原研机构

Teva Pharmaceutical Industries Ltd.

在研机构

哈药集团三精制药有限公司初创企业

The University of Texas MD Anderson Cancer Center

Teva Pharmaceutical Industries Ltd.

+ [2]

非在研机构

Cephalon, Inc.

ChemGenex Pharmaceuticals Pty Ltd.Teva Pharmaceuticals USA, Inc.

+ [1]

最高研发阶段批准上市

首次获批日期

美国 (2012-10-26),

加速期慢性骨髄性白血病

最高研发阶段(中国)批准上市

特殊审评快速通道 (美国)、加速批准 (美国)、孤儿药 (美国)

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结构

分子式C29H39NO9

InChIKeyHYFHYPWGAURHIV-JFIAXGOJSA-N

CAS号26833-87-4

关联

55

项与高三尖杉酯碱相关的临床试验

NCT06483906 / Recruiting临床2期IIT

Efficacy and Safety of Venetoclax and Azacitidine Combined With Low-Intensity Homoharringtonine Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Intermediate/High-Risk Newly Diagnosed Acute Myeloid Leukemia

This study is a single-center, single-arm, prospective phase II clinical trial evaluating the efficacy and safety of the VAH (Venetoclax and Azacitidine combined with Homoharringtonine) regimen, followed by allo-HSCT for intermediate and high-risk AML. Eligible patients receive two cycles of the VAH chemotherapy regimen. If minimal residual disease (MRD) is negative after these two cycles, patients proceed to the transplantation process. If MRD remains positive, patients receive an additional two cycles of the VAH regimen. Upon achieving MRD negativity, they then proceed to the transplantation process.
The conditioning regimen includes fludarabine at 30 mg/m²/day from day -7 to day -3 (5 days), cytarabine at 1-1.5 g/m²/day from day -7 to day -3 (5 days), and busulfan at 3.2 mg/kg/day from day -5 to day -3 (3 days). Conditioning begins on day -6, and donor hematopoietic stem cell infusion is performed on day 0.
All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year. If disease relapse is suspected during the follow-up period, bone marrow or extramedullary relapse site examinations will be conducted at any time.
The primary endpoint is the 1-year and 2-year overall survival (OS). Secondary endpoints include the complete response (CR) rate after 1 and 2 cycles of chemotherapy; 1-year and 2-year disease-free survival (DFS) following the achievement of CR through induction therapy; cumulative relapse rate; non-relapse mortality (NRM); incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant; and the cumulative incidence of chronic GVHD within 1 year and 2 years post-transplant.

开始日期2024-07-02

申办/合作机构

上海市第一人民医院

NCT06361329 / Recruiting临床3期IIT

A Multicenter, Prospective, Randomized Controlled Clinical Study Comparing the Efficacy of VHAG and Traditional Chemotherapy Regimens in the Treatment of Adult Newly Diagnosed Early Precursor T-cell Acute Lymphoblastic Leukemia (ETP-ALL)

ETP-ALL is a subtype of T-cell acute lymphoblastic leukemia (T-ALL) with poor outcomes and prognosis. Effective induction therapy is crucial in improving the treatment effect. Based on our laboratory research and clinical practice, the venetoclax plus HAG regimen shows promising efficacy in treating ETP-ALL. Therefore, we plan to conduct a prospective, multicenter Phase III clinical study to evaluate the efficacy of the venetoclax plus HAG regimen in treating newly diagnosed ETP-ALL patients.

开始日期2024-04-01

申办/合作机构

The First Affiliated Hospital, Zhejiang University School of Medicine

NCT06221683 / Recruiting临床2期IIT

A Multicenter Clinical Study of Molecular Subtyping Combined With MRD-driven Remission Induction Regimen in Children and Adolescents With AML: A Phase II Cohort Study (GMCAII)

The goal of this clinical trial is to estimate the rate (probability) of complete remission or complete remission with incomplete count recovery (CR/CRi) with negative MRD after induction I and II, event-free survival (EFS), and cumulative incidence (probability) of relapse (CIR), in patients receiving molecular/precision medicine and MRD-driven remission inductions, and to assess secondarily if there is an improvement over the AML2018 protocol.

开始日期2024-01-01

申办/合作机构-

100 项与高三尖杉酯碱相关的临床结果

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100 项与高三尖杉酯碱相关的转化医学

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100 项与高三尖杉酯碱相关的专利（医药）

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700

项与高三尖杉酯碱相关的文献（医药）

2024-10-23·COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING

Antiproliferative Activity of Cephalotaxus Esters: Overcoming Chemoresistance

Article

作者: Djaballah, Hakim ; Yong-Gonzalez, Vladimir ; Frattini, Mark G. ; Shum, David ; Gin, David Y. ; Calder, Paul A. ; Radu, Constantin

Introduction::

Omacetaxine, a semisynthetic form of Homoharringtonine (HHT), was approved for the treatment of Chronic Myeloid Leukemia (CML). Previously, we have published the synthesis of this natural alkaloid and three of its derivatives: Deoxyharringtonine (DHT), Deoxyhomoharringtonine (DHHT), and Bis(demethyl)-deoxyharringtonine (BDHT), and reported its refractory activity against the HL-60/RV+ cells over-expressing P-glycoprotein 1 (MDR1).

Methods::

In this study, we have explored the extent of this resistance by first expanding the panel of established cell lines and using a panel of 21 leukemia patient-derived primary cells.

Results::

Herein, we have reported consistent resistance to HTT of K562-derived cells and to mitoxantrone of MES-SA/MX2-derived cells; all of them have been found to overexpress MDR1, while we have found U87MG-ABCG2 and H69AR cells to be very sensitive to HTT. In contrast, DHT, DHHT, and BDHT seemingly overcame this resistance due to the changes made to the acyl chain of HTT, rendering the derivatives less susceptible to efflux. Surprisingly, the leukemia primary cells were very sensitive to HHT and its derivatives with low nanomolar potencies, followed by a new class of CDC7 kinase inhibitors, the anthracycline class of topoisomerase inhibitors, the DNA intercalator actinomycin-D, and the vinca alkaloid class of microtubule inhibitors. The mechanism of cell death induced by HTT and DHHT was found to be mediated via caspase 3 cleavage, leading to apoptosis.

Conclusion::

Taken together, our results confirm that HHT is a substrate for MDR1. It opens the door to a new opportunity to clinically evaluate HHT and its derivatives for the treatment of AML and other cancers.

2024-09-21·Journal of biomolecular structure & dynamics

A reverse docking approach to explore the anticancer potency of natural compounds by interfering metastasis and angiogenesis

Article

作者: Prome, Anindita Ash ; Bappy, Md Nazmul Islam ; Ahmed, Nadim ; Rani, Nurul Amin ; Patel, Harun ; Robin, Tanjin Barketullah ; Ahmad, Iqrar ; Zinnah, Kazi Md Ali

Angiogenesis, which results in the formation of new blood and lymph vessels, is required to serve metastatic cancer progression. Cancer medications may target these two interconnected pathways. Phytocompounds have emerged as promising options for treating cancer. In this study, we used a reverse docking strategy to find new candidate molecules for cancer treatment that target both pathways. Following a literature study, the important cancer-causing proteins vascular endothelial growth factor D (VEGF-D) and basic fibroblast growth factor (bFGF) for angiogenesis and matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) for the metastatic pathway were targeted. Protein Data Bank was used to retrieve the structures of chosen proteins. 22 significant plant metabolites were identified as having anticancer activity. To determine the important protein binding residues, active site prediction was used. Using Lenvatinib and Withaferin A as reference ligands, the binding affinity of certain proteins for plant metabolites was determined by docking analysis. Homoharringtonine and viniferin, both have higher binding affinities when compared to reference ligands, with docking scores of -180.96 and -180.36 against the protein MMP-9, respectively. Moreover, Viniferin showed the highest binding affinity with both MMP-9 and MMP-2 proteins, which were then subjected to a 100-ns molecular dynamic simulation. where they were found to be significantly stable. In pharmacoinformatics investigations, the majority of our compounds were found to be non-toxic for the host. In this study, we suggested natural substances as cutting-edge anticancer treatments that target both angiogenesis and metastasis, which may aid in accelerating drug development and identifying viable therapeutic candidates.Communicated by Ramaswamy H. Sarma.

2024-09-04·CANCER RESEARCH

Dotting Out AML by Targeting Fibrillarin

Review

作者: Luo, Hanzhi ; Kharas, Michael G.

Dysregulated biomolecular condensates, formed through multivalent interactions among proteins and nucleic acids, have been recently identified to drive tumorigenesis. In acute myeloid leukemia (AML), condensates driven by RNA-binding proteins alter transcriptional networks. Yang and colleagues performed a CRISPR screen and identified fibrillarin (FBL) as a new driver in AML leukemogenesis. FBL depletion caused cell cycle arrest and death in AML cells, with minimal impact on normal cells. FBL’s phase separation domains are essential for pre-rRNA processing, influencing AML cell survival by regulating ribosome biogenesis and the translation of oncogenic proteins like MYC. Therapeutically, the chemotherapeutic agent CGX-635 targets FBL, inducing its aggregation, impairing pre-rRNA processing, and reducing AML cell survival. This highlights FBL’s phase separation as a therapeutic vulnerability in AML. These findings suggest that targeting the phase separation properties of RNA-binding proteins could offer a novel and effective strategy for AML treatment. Further research into condensate dynamics in cancer and development of condensate-modulating drugs holds significant promise for future cancer therapies.

21

项与高三尖杉酯碱相关的新闻（医药）

2024-11-03

·生物谷

中山大学吴仲义/文海军团队开发广谱高效的抗冠状病毒药物

冠状病毒是导致呼吸道感染的主要病毒性病原体之一。自本世纪初以来，已经发生过3次由冠状病毒导致的大流行疾病，即SARS（2003年）、MERS（2012年）和由SARS-CoV-2导致的COVID-19，而且据估计这不会是最后一次。近期，由中山大学生命科学学院吴仲义教授领导的研究团队，在《国家科学评论》（National Science Review）上报导了一种广谱的高效抗冠状病毒药物——高三尖杉酯碱（homoharringtonine，HHT），有望成为应对冠状病毒未来疫情的第一道防线。冠状病毒是已知基因组最大的RNA病毒，全长在26~32kb之间。基因组5’端三分之二的区域编码一个长度约为8000个氨基酸的“超级蛋白”（ORF1ab），是病毒的非结构蛋白，主要负责病毒的复制；后端三分之一的基因组编码结构蛋白，负责病毒的侵袭和感染。冠状病毒进入宿主细胞后，首先以病毒基因组RNA为模板，利用宿主的核糖体翻译出ORF1ab，随后ORF1ab水解，产生16个非结构蛋白，其中包括病毒复制所需要的酶。吴仲义/文海军团队于2020年4月份通过分析新冠病毒的基因组结构特征，首先指出这种特殊的编码机制（先完整翻译出一个“超级蛋白”再水解）提高了冠状病毒的进化稳定性，有利于维持其巨大基因组的完整性，也是其“阿克琉斯之踵”；并推测在所有药物里最高效抑制“超级蛋白”合成的是高三尖杉酯碱 (homoharringtonine，HHT) (Wu and Wen 2020，Natl. Sci. Rev.)。HHT是我国于上世纪70年代（与青蒿素同时期）首先鉴定到的抗肿瘤药物，已在我国广泛应用超过40年的时间，其原料三尖杉是我国的特产植物。在此基础上，吴仲义/文海军团队通过与国内多家P3/P4实验室合作，证实HHT能在纳摩尔水平广谱抑制多种冠状病毒（包括新冠病毒的beta、delta、omicron株，以及猪流行性腹泻病毒(PEDV)、猪丁型冠状病毒(PDCoV)和猪急性腹泻综合征冠状病毒(SADS-CoV)）的复制，并且在多种动物模型中展现出优异的抗冠状病毒活性，效果远优于已上市的多种小分子药物，包括瑞德西韦、莫那匹拉韦、以及Paxlovid等。特别是在新冠疫情后期通过临床研究证实，滴鼻给药HHT能在安全剂量下快速清除受试者体内的病毒，从而为将HHT开发为应对冠状病毒未来疫情的广谱高效药物奠定了坚实的基础。本研究得到了国家自然科学基金委重大项目、“抗新型冠状病毒药物关键科学问题研究”专项项目，广东省生物安全专项项目的大力支持。中山大学生命科学学院吴仲义教授、广东祈福医院蔡绮纯教授、中科院武汉病毒所王曼丽教授、杭州民生制药李健博士为本文通讯作者。图：HHT有望成为应对冠状病毒未来疫情的第一道防线论文链接： https://academic-oup-com.libproxy1.nus.edu.sg/nsr/advance-article/doi/10.1093/nsr/nwae382/7845890 本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

临床研究紧急使用授权

2024-10-22

·Insight数据库

恒瑞、翰森制药、正大天晴等企业创新药又有新进展，多个关键 Ⅲ 期临床启动

启动 Ⅲ 期临床，意味着新药研发距离上市又近了一大步。10 月（数据范围 10.1-10.22），多款国产创新药进入关键 Ⅲ 期临床，这些新药进展涉及恒瑞、瀚森制药、正大天晴、亚盛医药、宜明昂科、宜联生物等企业，我们从中选择部分重点项目跟大家分享。恒瑞两款 GLP-1R 激动剂启动 Ⅲ 期临床用于 2 型糖尿病 10 月 21 日，恒瑞在国内启动一项 HRS9531 用于 2 型糖尿病的 Ⅲ 期临床研究。截图来源：CDE 官网 HRS9531 是恒瑞研发的一种 GLP-1/GIP 双受体激动剂，目前正在开展用于肥胖、2 型糖尿病、多囊卵巢综合征、射血分数保持的心力衰竭合并肥胖等适应症，其中，用于肥胖和 2 型糖尿病已经进展到 Ⅲ 期临床阶段。 10 月 15 日，恒瑞在国内启动一项诺利糖肽注射液（SHR20004）用于 2 型糖尿病的 Ⅲ 期临床。截图来源：CDE 官网诺利糖肽是一种 GLP-1 受体激动剂，给药频率为一天一次皮下注射，目前在研适应症主要为肥胖和 2 型糖尿病，其中，肥胖适应症目前正处于 II 期临床。宜明昂科「替达派西普」首次启动慢性单核细胞白血病 Ⅲ 期临床 10 月 18 日，宜明昂科在 Clinicaltrial 网站登记一项国内Ⅲ期临床（NCT06647862），旨在评估替达派西普联合阿扎胞苷与安慰剂联合阿扎胞苷治疗初诊慢性单核细胞白血病（CMML1-2）患者的疗效和安全性。截图来源：Clinicaltrials 替达派西普（IMM01）是宜明昂科自主研发的新一代 CD47 靶向分子。该药具有双重机制，既能够阻断来自肿瘤的「别吃我」信号，也能通过 IgG1 激活患者免疫系统的「吃我」信号。此前该药已在国内启动用于经典型霍奇金淋巴瘤三线治疗的关键 Ⅲ 期临床。本次启动的是替达派西普首个慢性粒单核细胞白血病 Ⅲ 期临床。今年 ESMO 上口头报告的 II 期研究结果显示，替达派西普联合阿扎胞苷针对初治的慢性粒-单核细胞白血病患者具有良好的疗效和耐受性：治疗≥4 个月的患者，总体缓解率 (ORR) 为 87.5%，完全缓解率 (CR) 为 37.5%; 治疗≥6 个月的患者，ORR 为 84.6%，CR 为 46.2%。恒瑞 Claudin18.2 ADC 首次启动胃癌 Ⅲ 期临床 10 月 18 日，恒瑞在 Clinicaltrial 网站登记一项国内Ⅲ期临床（NCT06649292），以比较 SHR A1904 与研究者选择的治疗在 Claudin18.2 阳性二线晚期或转移性胃或胃食管交界处腺癌患者中的疗效。截图来源：Clinicaltrials SHR-A1904 是恒瑞自主研发的 Claudin 18.2 ADC。去年 10 月，德国默克通过和恒瑞达成一项高达 14 亿欧元的合作，获得了 SHR-A1904 和恒瑞另一款产品 HRS-1167（第二代 PARP 抑制剂）在中国大陆以外地区的开发、生产和商业化的独家权利。今年 ESMO 年会上，恒瑞首次公布了 SHR-A1904 治疗胃或胃食管交界处癌（GC/GEJC）的 I 期研究结果。数据显示：在基线和≥1 次基线后评估的患者中，6.0 mg/kg 剂量组中，ORR 和 DCR 分别为 55.6% (5/9) 和 88.9% (8/9)；8.0 mg/kg 剂量组中，ORR 和 DCR 分别为和 36.7% (11/30) 和 86.7% (26/30)。亚盛医药 Bcl-2 抑制剂首次启动 MDS 适应症 Ⅲ 期临床 10 月 15 日，亚盛医药在 Clinicaltrial 网站登记一项全球多中心Ⅲ期临床（NCT06641414，GLORA-4），该研究将在美国和中国内地开展，以评估 Lisaftoclax (APG-2575) 联合阿扎胞苷 (AZA) 治疗新诊断的高风险骨髓增生异常综合征 (HR-MDS) 患者的疗效，对照组为安慰剂联合阿扎胞苷。截图来源：Clinicaltrials APG-2575 是亚盛自主研发的新型口服 Bcl-2 选择性抑制剂。此前，该药已启动两型关键 Ⅲ 期临床，针对的适应症分别为慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（一线）、急性髓系白血病（一线）。 23 年 ASH 年会上，亚盛曾公布了 APG-2575 单独使用或与阿扎胞苷或高三尖杉酯碱联合使用对 AML、MDS 或其他髓系肿瘤成人患者的安全性、药代动力学 (PK) 和疗效数据。其中，针对 MDS 患者的亚组数据显示，ORR 为 70.0%，CR/CRi 率为 60.0%。翰森制药 TYK2 抑制剂启动首个 Ⅲ 期临床 10 月 14 日，翰森制药登记一项国内 Ⅲ 期临床（CTR20243822），以评估 HS-10374 治疗成年中重度斑块状银屑病患者的有效性和安全性。这也是 HS-10374 启动的首个关键性注册 Ⅲ 期临床。截图来源：CDE 官网 HS-10374 是翰森制药自主研发的一款酪氨酸激酶 2（TYK2）选择性变构抑制剂。在今年 10 月刚举行的第 33 届欧洲皮肤病与性病学会年会（EADV 2024）上，翰森制药口头报告了 HS-10374 银屑病 Ⅱ 期临床研究结果数据：在 PASI75 应答率方面，HS-10374 6 mg 组为 28.6%（P=0.013），12 mg 组为 72.1%（P<0.001），均显著高于安慰剂组的7.5%，达到主要终点； HS-10374 6 mg 组和 12 mg 组的 sPGA 0/1 应答率（分别为 33.3%、65.1%）也显著高于安慰剂组（10.0%）。此外，HS-10374 治疗银屑病具有良好的安全性正大天晴罗伐昔替尼启动 Ⅲ 期临床用于移植物抗宿主病 10 月 11 日，正大天晴 1 类新药启动一项 Ⅲ 期临床研究，评价罗伐昔替尼对比研究者选择的方案在三线及以后中重度慢性移植物抗宿主病中有效性和安全性。截图来源：CDE 官网罗伐昔替尼是一款具有全新化学结构的 JAK/ROCK 抑制剂，今年 7 月 13 日已经在国内首次申报上市，用于治疗中高危骨髓纤维化。正大天晴在 2023EHA 年会上公布的 Ib/II 期临床研究数据表明，罗伐昔替尼在 cGVHD 患者中，毒性可耐受，对各排异器官部位最佳客观缓解率 86.7%，40% 患者 LSS 评分改善≥7 分，73.3% 患者降低激素使用剂量，有望为 cGVHD 患者带来更多的临床治疗选择。三生国建启动 IL4R 单抗 Ⅲ 期临床用于慢性鼻窦炎伴鼻息肉病 10 月 10 日，CDE 官网显示，三生国建登记一项在慢性鼻窦炎伴鼻息肉（CRSwNP）受试者中评估 SSGJ-611 的有效性与安全性的多中心、随机、双盲、安慰剂对照 Ⅲ 期临床研究。截图来源：CDE 官网 SSGJ-611 是三生国建自主研发的 IL-4Rα拮抗剂。今年 8 月 9 日，三生国建宣布 SSGJ-611 治疗慢性鼻窦炎伴鼻息肉 II 期临床研究达到主要终点。结果显示，在治疗第 16 周时，两个剂量组双侧鼻内镜下鼻息肉评分（NPS）较基线变化分别为-2.12 和-1.61，周平均鼻塞评分（NCS）较基线变化分别为-1.11 和-1.16。相较于国外已上市的同靶点药物度普利尤单抗在治疗成人 CRSwNP 受试者的临床研究中（SINUS-24 和 SINUS-52 两个研究），第 24 周 NPS 较基线分别降低-1.89 和-1.71。可以看出，SSGJ-611 治疗 CRSwNP 受试者，在第 16 周的疗效应答，与度普利尤单抗第 24 周的应答相似甚至显示较其有更高的疗效趋势（此非头对头对照研究），提示 SSGJ-611 有显著改善 CRSwNP 疾病的潜力。宜联生物 B7-H3 ADC 启动鼻咽癌 Ⅲ 期临床 10 月 8 日，宜联生物在 Clinicaltrials 登记一项 YL201 用于鼻咽癌（NPC）三线/末线疗法的 Ⅲ 期临床，这是继小细胞肺癌之后，该新药启动的第二个 Ⅲ 期临床研究。截图来源：Clinicaltrials YL201 是一种靶向 B7-H3 的 ADC，具有肿瘤微环境可激活连接子和新型拓扑异构酶 I 抑制剂有效载荷。在今年 ESMO 大会上，宜联生物公布了 YL201 在实体瘤患者中的初步临床结果，其中，NPC 队列共计 70 例可评估疗效的患者，既往全部接受过含铂化疗和 anti-PD-(L)1 治疗，75% 接受过 2 线及以上标准治疗。 YL201 在 NPC 患者中的 ORR 为 48.6%（≥2.0 mg/kg ORR 为 48.6%），mPFS 为 7.2 个月（≥2.0 mg/kg mPFS 为 7.2 个月）。在接受过 2 线及以上标准治疗的患者中，ORR 为 51.0%，mPFS 为 7.0 个月，与 NPC 总体人群相当。封面来源：站酷海洛 Plus 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：vvy PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验点击阅读原文，立刻解锁！

临床3期抗体药物偶联物临床2期

2024-06-21

·BioSpace

Tectonic Completes Reverse Merger With Avrobio, Starts Trading on Nasdaq

Pictured: Nasdaq headquarters in New York City/iStock, JHVEPhoto Tectonic Therapeutic completed its reverse merger with Avrobio on Thursday, with plans to begin trading Friday on the Nasdaq under the ticker symbol TECX. The biotech also completed a $130 million private placement with a group of new and existing investors, concurrent with the reverse merger. The fresh capital plus cash on hand are expected to fund operations into mid-2027. “We believe we are strongly positioned to enter the public markets at this time, with a solid financial foundation, investor syndicate and leadership team, and with several potential catalysts over the next two years, setting the stage for meaningful value creation,” Tectonic CEO Alise Reicin said in a statement. Tectonic is developing GPCR-targeted therapeutic proteins for indications currently underserved by small molecule treatments. Its GEODe platform is intended to overcome the common challenges of GPCR-targeted biologics. The new company will take Tectonic’s lead program into a Phase II trial for a population of Pulmonary Hypertension patients in the second half of this year. TX45 is a fusion molecule that activates the GPCR target of the hormone relaxin. Relaxin had been considered a “wonder drug” for cardiovascular benefits, but previous studies have failed to produce those benefits in the clinic. Tectonic believes its protein engineering has potential to overcome those limitations to develop relaxin as a therapeutic. A clinical candidate is being selected for its second program to treat hereditary hemorrhagic telangiectasia (HHT) later this year, with studies commencing by the end of 2025 or start of 2026. HHT is the second most common genetic bleeding disorder. The program has first-in-indication potential. Prior to the merger, Avrobio was focused on curative Hematopoietic stem cells (HSC) gene therapies. After announcing positive Phase I/II results in May 2023, the company sold its HSC gene therapy program for cystinosis to Novartis in June of that year for $87.5 million. In January 2024, Avrobio announced it was halting program development and exploring strategic alternatives including a merger. As part of the closing of the merger with Tectonic, Avrobio exercised a 1 for 12 reverse stock split of its common stock. With the closing of the merger, prior Avrobio stockholders own approximately 24.8% on a diluted basis and prior Tectonic stockholders hold approximately 75.2% of the combined company's outstanding common stock on a diluted basis. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.

并购基因疗法临床2期

100 项与高三尖杉酯碱相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08956	高三尖杉酯碱	L01XX40	DB04865

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
加速期慢性骨髄性白血病	美国	Teva Pharmaceuticals International GmbH	2012-10-26
骨髓增生异常综合征	中国	哈药集团三精制药有限公司初创企业	-
费城染色体阳性慢性粒细胞白血病	中国	哈药集团三精制药有限公司初创企业	-
真性红细胞增多症	中国	哈药集团三精制药有限公司初创企业	-

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
急性双表型白血病	临床2期	美国	The University of Texas MD Anderson Cancer Center	2021-12-17
复发性骨髓增生异常综合征	临床2期	美国	The University of Texas MD Anderson Cancer Center	2021-12-17
难治性急性髓细胞白血病	临床2期	美国	The University of Texas MD Anderson Cancer Center	2021-12-17
难治性骨髓增生异常综合征	临床2期	美国	The University of Texas MD Anderson Cancer Center	2021-12-17
白血病	临床2期	美国	Teva Pharmaceuticals USA, Inc.	2015-05-18
急性红细胞白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
急性巨核细胞白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
伴有 11q23 异常的急性髓系白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
急性髓细胞白血病伴多系发育不良	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01
急性髓单核细胞白血病	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-07-01

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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


ASH2023	N/A	复发性急性髓细胞白血病	321	VEN plus AZA and HHT (VAH)	廠廠簾製蓋繭鹹膚獵衊(壓積繭構選襯構餘醖窪) = 觸製廠構襯遞憲繭蓋鏇顧憲繭艱廠蓋壓淵積蓋 (餘顧膚壓廠膚願鑰襯鹹 ) 更多	-	2023-12-11
ASH2023	N/A	复发性急性髓细胞白血病	321	VEN plus AZA (VA)	廠廠簾製蓋繭鹹膚獵衊(壓積繭構選襯構餘醖窪) = 夢膚觸襯築衊鹹遞壓膚顧憲繭艱廠蓋壓淵積蓋 (餘顧膚壓廠膚願鑰襯鹹 ) 更多	-	2023-12-11
ASH2023	N/A	成人急性髓性白血病	25	Venetoclax	鏇齋網鏇壓鑰齋鑰夢構(廠夢遞夢鏇觸鬱選遞糧) = The most frequent hematological adverse events were Grade 3 to 4 anemia, thrombocytopenia, and neutropenia during the induction treatment and occurred in all patients (25/25 100%) 醖積繭鏇獵遞憲遞範築 (壓膚願鏇鏇鹹壓顧願窪 ) 更多	-	2023-12-10
EHA2023	N/A	复发性急性髓细胞白血病	32	Venetoclax+Azacitidine+Homoharringtonine+Cytarabine	糧積憲鏇獵觸窪襯鹹醖(顧觸鬱築願廠淵選簾衊) = 選築築襯製網簾鑰鹹觸廠鹹艱餘鏇餘築憲廠襯 (獵網窪窪蓋齋遞膚獵簾 ) 更多	-	2023-06-08
RJ-AML 2014 (Pubmed \| Am J Hematol)	临床2期	急性髓性白血病	151	Idarubicin and cytarabine with homoharringtonine	簾獵觸醖襯醖積廠觸鏇(淵鹽糧壓遞範淵網淵鹹) = 醖選繭艱憲範築壓餘鏇憲鑰襯遞襯廠艱積壓獵 (齋壓壓廠簾窪衊艱襯鏇 )	-	2021-10-23
NCT02440568 (CTgov)	临床1/2期	急性髓性白血病	22	Omacetaxine+Cytarabine+Idarubicin (Patients With Newly Diagnosed AML, Cohort 1)	壓鬱鏇壓憲廠網膚衊鏇(餘製鑰鑰齋齋壓鬱憲顧) = 衊艱簾蓋鏇襯顧繭網鹽繭淵夢獵範鹹遞積繭觸 (齋繭鏇獵淵醖膚網鏇襯, 製鏇壓積蓋遞糧壓鏇築 ~ 網選蓋積膚獵衊製齋壓) 更多	-	2021-07-06
NCT02440568 (CTgov)	临床1/2期	急性髓性白血病	22	Omacetaxine+Cytarabine+Idarubicin (Patients With Newly Diagnosed AML, Cohort 2)	壓鬱鏇壓憲廠網膚衊鏇(餘製鑰鑰齋齋壓鬱憲顧) = 襯遞夢廠顧窪窪蓋廠蓋繭淵夢獵範鹹遞積繭觸 (齋繭鏇獵淵醖膚網鏇襯, 積鑰觸膚範構醖顧範繭 ~ 鏇艱糧顧淵鹹鹽齋餘齋) 更多	-	2021-07-06
NCT01873495 (CTgov)	临床2期	急性髓性白血病	7	Omacetaxine	鹽襯網網繭齋鏇鑰顧範(簾鬱艱糧餘製餘鑰築醖) = 網觸窪選繭糧鑰積觸憲膚鹹艱鏇壓構鏇壓選糧 (餘鏇艱蓋鹽壓壓鑰鏇積, 壓壓築壓簾蓋鹽構願窪 ~ 鏇艱顧艱糧襯鏇夢遞鑰) 更多	-	2019-09-24
NCT02078960 (CTgov)	临床1/2期	费城染色体阳性慢性粒细胞白血病 \| 加速期慢性骨髄性白血病	10	omacetaxine (Cohort 1)	繭獵簾築齋艱築簾糧簾(繭淵襯衊築遞糧構醖淵) = 淵衊鏇齋鹽衊衊築鑰鹽鑰鏇醖醖製鏇糧壓積築 (鬱襯壓範鹹網構繭繭餘, 淵窪壓鏇憲觸衊壓鏇獵 ~ 餘衊簾醖鑰鬱齋膚網鏇) 更多	-	2019-01-14
NCT02078960 (CTgov)	临床1/2期	费城染色体阳性慢性粒细胞白血病 \| 加速期慢性骨髄性白血病	10	omacetaxine (Cohort 2)	繭獵簾築齋艱築簾糧簾(繭淵襯衊築遞糧構醖淵) = 網淵選鏇顧廠選構餘獵鑰鏇醖醖製鏇糧壓積築 (鬱襯壓範鹹網構繭繭餘, 憲簾廠範繭鑰蓋鏇遞鹽 ~ 醖齋壓鹽夢繭網製膚艱) 更多	-	2019-01-14
NCT02440568 (ASH2018) 人工标引	临床1/2期	急性髓性白血病一线	22	cytarabine+idarubicin+Omacetaxine mepesuccinate	憲鹹艱遞顧顧願壓獵膚(醖願膚鹽選淵餘網簾簾) = fever (68%), nausea (64%), vomiting (55%), hyperglycemia (41%), diarrhea (41%), mucositis (36%), headache (36%), sinus tachycardia (32%), rash/dermatitis (32%), and abdominal pain (32%) 艱顧鹹餘夢膚壓衊築積 (壓構餘壓廠夢蓋淵鹽繭 )	积极	2018-11-29
NCT01272245 (CTgov)	临床2期	急性髓性白血病 \| 骨髓增生异常综合征	36	Omacetaxine+cytarabine	襯範壓選鹹願製糧膚築(鏇遞蓋襯窪網網淵艱積) = 蓋願顧餘夢鬱選鹽顧網範蓋積襯願糧製築網壓 (壓範窪獵構築膚鬱廠願, 餘積廠鬱淵夢願觸糧遞 ~ 鹽廠艱鏇顧窪範獵築憲) 更多	-	2018-05-30
NCT02029417 (CTgov)	临床2期	复发性急性髓细胞白血病 \| 急性单核细胞白血病 \| 伴del(5q)成人急性髓系白血病 ... 更多	2	laboratory biomarker analysis+omacetaxine mepesuccinate+decitabine+cytarabine	顧餘構遞齋壓鹹齋艱艱(鑰蓋淵糧築襯鹽鹽繭廠) = 淵顧鬱夢範廠積鹹簾廠築廠壓廠襯糧鏇廠衊壓 (壓衊鹹廠憲蓋鏇壓襯糧, 簾顧艱選積窪膚繭觸齋 ~ 窪鏇築鑰餘壓襯襯獵夢) 更多	-	2016-05-09