This is a multicenter, open-label, single-arm, phase II study to evaluate the efficacy, safety, and pharmacokinetics of NHWD-870 HCl in adults and adolescents with advanced NUT cancer.

开始日期2024-04-25

申办/合作机构

浙江文达医药科技有限公司

CTR20231874

/ Recruiting临床2期

NHWD-870 HCl治疗复发或难治性弥漫大B细胞淋巴瘤的多中心、开放、单臂、II期临床研究

评价 NHWD-870 HCl 治疗复发或难治性弥漫大B细胞淋巴瘤的抗肿瘤活性。

开始日期2023-10-26

申办/合作机构

浙江文达医药科技有限公司

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100 项与 NHWD-870 相关的临床结果

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100 项与 NHWD-870 相关的转化医学

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100 项与 NHWD-870 相关的专利（医药）

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项与 NHWD-870 相关的文献（医药）

2025-05-01·Bioactive Materials

TME-responsive nanocomposite hydrogel with targeted capacity for enhanced synergistic chemoimmunotherapy of MYC-amplified osteosarcoma

Article

作者: He, Chuanglong ; Ma, Xiaojun ; Wu, Jiangpeng ; Lai, Peng ; Ma, Yichao ; Zhou, Xiaojun ; Sha, Zhou ; Li, Bing

The oncogene MYC is one of the most commonly activated oncogenic proteins in human tumors, with nearly one-fourth of osteosarcoma showing MYC amplification and exhibiting the worst clinical outcomes. The clinical efficacy of single radiotherapy, chemotherapy, and immunotherapy for such osteosarcoma is poor, and the dysregulation of MYC amplification and immune-suppressive tumor microenvironment (TME) may be potential causes of anti-tumor failure. To address the above issues, we developed an injectable TME-responsive nanocomposite hydrogel to simultaneously deliver an effective MYC inhibitor (NHWD-870) and IL11Rα-targeted liposomes containing cisplatin-loaded MnO₂ (Cis/Mn@Lipo-IL11). After in situ administration, NHWD-870 effectively degrades MYC and downregulates CCL2 and IL13 cytokines to trigger M1 type activation of macrophages. Meanwhile, targeted delivery of Cis/Mn@Lipo-IL11 reacts with excess intratumoral GSH to generate Mn²⁺ and thus inducing excess active oxygen species (ROS) production through Fenton-like reaction, along with cisplatin, thereby inducing immunogenic cell death (ICD) to promote dendritic cell maturation. Through synergistic regulation of MYC and ICD levels, the immune microenvironment was reshaped to enhance immune infiltration. In the osteosarcoma-bearing model, the nanocomposite hydrogel significantly enhanced tumor T cell infiltration, induced effective anti-tumor immunity and attenuated lung metastasis. Therefore, our results reveal a powerful strategy for targeted combination therapy of MYC-amplified osteosarcoma.

2024-04-01·European journal of pharmacology

A BET inhibitor, NHWD-870, can downregulate dendritic cells maturation via the IRF7-mediated signaling pathway to ameliorate imiquimod-induced psoriasis-like murine skin inflammation

Article

作者: Kuang, Yehong ; Yin, Mingzhu ; Chen, Wangqing ; Zhu, Wu ; Pei, Shiyao ; Dong, Liang ; Chen, Xiang ; Jin, Liping

Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of dendritic cells (DCs), which are primarily responsible for initiating an immune response. The bromodomain and extraterminal domain (BET) family plays a pivotal role in the transcriptional regulation of inflammation and its inhibitors can downregulate DCs maturation and activation. Here we investigated the effect of NHWD-870, a potent BET inhibitor, on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS) and IMQ. Application of NHWD-870 significantly ameliorated IMQ-triggered skin inflammation in mice, and markers associated with DC maturation (CD40, CD80 and CD86) were decreased in skin lesions, spleen and lymph nodes. Additionally, NHWD-870 reduced LPS or IMQ induced DCs maturation and activation in vitro, with lower expression of inflammatory cytokines [interleukin (IL)-12, IL-23, tumor necrosis factor-α, IL-6, IL-1β, chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10]. In addition, we found that interferon regulatory factor 7 (IRF7) significantly increased during DCs maturation, and inhibition of IRF7 could impair BMDCs maturation and activation. What's more, IRF7 was highly expressed in both psoriatic patients and IMQ-induced psoriasis-like mice. Single-cell RNA sequencing of normal and psoriatic skin demonstrated that IRF7 expression was increased in DCs of psoriatic skin. While NHWD-870 could inhibit IRF7 and phosphorylated-IRF7 expression in vivo and in vitro. These results indicate that NHWD-870 suppresses the maturation and activation of DCs by decreasing IRF7 proteins which finally alleviates psoriasis-like skin lesions, and NHWD-870 may be a potent therapeutic drug for psoriasis.

2024-02-01·Experimental eye research

IL1R2 promotes retinal angiogenesis to participate in retinopathy of prematurity by activating the HIF1α/PFKFB3 pathway

Article

作者: Liu, Li ; Li, Qiaolian ; Zhou, Na

Retinopathy of prematurity (ROP) is the leading cause of blindness in children, but there is no safe and effective treatment available. Interleukin-1 receptor type 2 (IL1R2) acts as a decoy receptor for IL-1 may affect ROP progression. This study aimed to investigate the role of IL1R2 in ROP. A microglial cell model was established under hypoxia conditions and co-cultured with choroidal endothelial cells, while an oxygen-induced retinopathy (OIR) model was also established. Microglial activation and IL1R2 levels in retinal tissues were analyzed using immunofluorescence assay. Endothelial cell migration was evaluated by Transwell assay and scratch test, angiogenesis was assessed using ELISA and tube formation assay, and proliferation was evaluated by EdU assay. The HIF1α/PFKFB3 pathway was analyzed by western blot. We observed that IL1R2 expression was predicted to be upregulated in ROP and was increased in hypoxia-treated BV2 cells. Additionally, IL1R2 levels were upregulated in the retinal tissues of OIR mice and correlated with microglial activation. In vitro experiments, we found that hypoxia promoted endothelial cell migration, angiogenesis, proliferation, and activated the HIF1α/PFKFB3 pathway, which were rescued by IL1R2 knockdown. Moreover, NHWD-870 (a HIF1α/PFKFB3 pathway inhibitor) suppressed endothelial cell migration, angiogenesis, and proliferation induced by IL1R2 overexpression. In conclusion, IL1R2 facilitates the migration, angiogenesis, and proliferation of choroidal endothelial cells by activating the HIF1α/PFKFB3 pathway to regulate ROP progression.

项与 NHWD-870 相关的新闻（医药）

2023-09-11

·SYNAPSE

Brief Discussion on Clinically Under-Investigation BRD4 Inhibitors

Bromodomain (BRDs) is a conserved protein structural domain that can specifically recognize acetylated lysine residues in proteins. Based on their structure and sequence similarity, 61 human bromodomains are classified into eight families, among which the BET family proteins, including BRD2, BRD3, BRD4, and BRDT are the most representative. The BET family bromodomain protein BRD4 contains acetylated lysine residues capable of binding chromatin and other proteins, which play a crucial role in gene regulation and cell growth control. BRD4 is associated with large protein complexes involved in regulating gene transcription, including mediator, PAFc, and super elongation complex, etc. The kinase activity of BRD4 can directly phosphorylate and activate RNA polymerase II, thereby regulating gene transcription expression. Many human diseases are closely related to BRD4 protein, such as tumors, autoimmune or inflammatory diseases, viral infections, and so on. BRD4 inhibitors target BRD4 for inhibition, which hold tremendous value in anti-cancer and anti-inflammatory sectors, as well as many other fields. It continues to attract the attention of major pharmaceutical companies and research institutions. BRD4 Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 8 Sep 2023, there are a total of 76 BRD4 drugs worldwide, from 62 organizations, covering 57 indications, and conducting 58 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The analysis of the target BRD4 reveals a competitive landscape with multiple companies actively involved in its development. Resverlogix Corp., Shenzhen Hepalink Pharmaceutical Group Co., Ltd., and Daiichi Sankyo Co., Ltd. are among the companies showing significant progress in their R&D efforts. The approved indications for drugs targeting BRD4 cover a wide range of diseases, indicating its potential as a therapeutic target. Small molecule drugs and PROTACs are the drug types progressing most rapidly, suggesting intense competition in the market. The countries/locations with active development include the United States, European Union, China, and others. China has shown progress in the development of BRD4 drugs. Overall, the target BRD4 presents a promising opportunity for pharmaceutical companies, with a diverse range of indications and active research and development efforts worldwide. BRD4 Inhibitor in Phase III Clinical Trials: ApabetaloneApabetalone is a small molecule drug that targets BRD4, a protein involved in various cellular processes. It has shown potential therapeutic benefits in a wide range of therapeutic areas, including immune system diseases, infectious diseases, urogenital diseases, respiratory diseases, nervous system diseases, cardiovascular diseases, congenital disorders, endocrinology, and metabolic diseases. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. In terms of active indications, Apabetalone has demonstrated efficacy in COVID-19, coronary artery disease, type 2 diabetes mellitus, atherosclerosis, acute coronary syndrome, hypercholesterolemia, kidney failure, chronic, Fabry disease, prediabetic state, diabetic nephropathies, pulmonary arterial hypertension, and HIV infections. This suggests that the drug may have a broad spectrum of applications in treating various diseases and conditions. Apabetalone is developed by Resverlogix Corp., an originator organization specializing in the pharmaceutical industry. Currently, the drug is currently in Phase 3 of clinical development. This indicates that it has progressed through earlier stages of testing and is now being evaluated in larger populations to assess its safety and efficacy. Furthermore, Apabetalone has been granted Breakthrough Therapy designation, a regulatory status that recognizes its potential to provide significant benefits over existing treatments for serious or life-threatening conditions. This designation highlights the drug's potential to address unmet medical needs and expedite its development and review process. In summary, Apabetalone is a small molecule drug that targets BRD4 and has shown promise in various therapeutic areas, including immune system diseases, infectious diseases, urogenital diseases, respiratory diseases, nervous system diseases, cardiovascular diseases, congenital disorders, endocrinology, and metabolic diseases. It is currently in Phase 3 of development and has been granted Breakthrough Therapy designation, indicating its potential to address unmet medical needs. BRD4 inhibitor entering Phase II Clinical Trials: NHWD-870NHWD-870 is a small molecule drug developed by Ningbo Wenda Pharma. It is designed to target BRD4, a protein that plays a role in various diseases. The drug is currently in Phase 2 of clinical trials, both globally and in China. The therapeutic areas that NHWD-870 aims to address include neoplasms (abnormal growth of cells), immune system diseases, hemic and lymphatic diseases, skin and musculoskeletal diseases, and respiratory diseases. This indicates that the drug has potential applications in a wide range of medical conditions. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. The active indications for NHWD-870 are diffuse large B-cell lymphoma, melanoma (cutaneous malignant), non-Hodgkin lymphoma, non-small cell lung cancer, and small cell lung cancer. These are all serious and life-threatening diseases, highlighting the importance of developing effective treatments in these areas. Ningbo Wenda Pharma is the originator organization behind NHWD-870. As the developer of the drug, they are responsible for its research, development, and clinical trials. The fact that NHWD-870 has reached Phase 2 in both global and Chinese trials suggests that it has shown promising results in earlier stages of testing. Overall, NHWD-870 is a small molecule drug that targets BRD4 and has potential applications in various therapeutic areas, including neoplasms, immune system diseases, hemic and lymphatic diseases, skin and musculoskeletal diseases, and respiratory diseases. Its active indications include diffuse large B-cell lymphoma, melanoma, non-Hodgkin lymphoma, non-small cell lung cancer, and small cell lung cancer. Developed by Ningbo Wenda Pharma, NHWD-870 has reached Phase 2 in clinical trials, indicating its potential as a treatment option for these serious medical conditions.

2023-03-14

·CPHI制药在线

关注 | 裁员17%，管线砍掉大半，这家德国药企的“保留项目”有何看点？

关注并星标CPHI制药在线近日，德国慕尼黑MorphoSys AG宣布计划停止所有临床前管线，并裁减17%的员工，以延长其现金跑道，届时MorphoSys将有110名员工失业。公司表示，后续将其主要资源集中于3款抗肿瘤药物。这三款仅存的产品分别是已上市的CD19抗体tafasitamab，在研产品BET抑制剂pelabresib及EZH2抑制剂CPI-0209。 CD19抗体tafasitamab Tafasitamab是一款靶向CD19的人源化单克隆抗体，也是目前MorphoSys AG唯一商业化上市的产品。2020年8月，FDA加速批准Tafasitamab上市，用来与来那度胺联用二线治疗成人复发或难治性（r/r）弥漫性大B细胞淋巴瘤（DLBCL）。2021年6月，欧洲药品管理局CHMP发表了积极意见，建议有条件批准tafasitamab和来那度胺联合治疗及后续tafasitamab单药治疗，用于不符合自体干细胞移植（ASCT）条件的r/r DLBCL成人患者的治疗。 Tafasitamab在开发过程中，使用Xmab技术平台，对抗体的Fc段进行改造，通过改造抗体的Fc端，能够将抗体与Fcγ受体的亲和力提高数十倍，从而更好地激活NK细胞、巨噬细胞等免疫细胞。临床数据表明，在使用来那度胺和Tafasitamab联合治疗r/r DLBCL成人患者中，试验数据显示：客观缓解率（ORR）为55%，完全缓解率（CR）为37％，部分缓解率（PR）为18％；中位缓解持续时间（mDOR）为21.7个月。最常见的不良反应是中性粒细胞减少。看到CD19这个靶点以及DLBCL，就会联想到CD19-CAR-T。虽然Tafasitamab临床效果稍逊一筹，但Tafasitamab的安全性更好，目前上市的CAR-T具有免疫相关不良反应，严重者甚至收到FDA的黑框警告，而Tafasitamab相关的不良反应主要为中性粒细胞减少。另外，目前上市的CAR-T产品多为自体来源，耗时长且价格昂贵，Tafasitamab则是一种工业化生产的即用型产品。 BET抑制剂pelabresib Pelabresib是一款潜在FIC的BET抑制剂，其用于治疗骨髓纤维化的III期MANIFEST-2研究正在进行中，将于明年初公布关键数据。 BET（溴结构域和超末端结构域）属于BD（溴结构域）大家族的一员，BD是一类由约110个氨基酸组成的、能够特异性识别组蛋白中乙酰化赖氨酸（KAc）的高度保守的蛋白结构域，其包含八大家族，其中BET是被研究较多的一个家族。 BET蛋白家族包含四个异构体，分别是：BRD2、BRD3、BRD4和BRDT。每个家族成员含有两个溴结构域（BD1、BD2）和一个超末端结构域（ET）。其中BD1和BD2识别并结合KAc从而发挥生理作用，ET结构域与辅助因子相互作用。BET家族蛋白通过BD1、BD2与乙酰化的染色质结合，从而在表观遗传学水平上对基因表达进行调控，广泛参与细胞周期、细胞分化、信号转导等过程，在许多肿瘤的发生、发展中起着重要作用。目前，一系列BET抑制剂正在研发中，不过BET抑制剂的研发极具挑战。这是因为BD1和BD2具有高度同源性，之前报道的大多BET抑制剂对BD1和BD2具有相似的亲和活性，这类抑制剂通常被称为泛BET抑制剂，如二氮杂及其衍生物（JQ1、IBET762、OTX015）等。这类抑制剂不但具有剂量限制性毒性而且其抗肿瘤活性比临床前观察到的弱。为了解决这些问题，开发高亚型选择性的BET抑制剂是未来的研发方向，这些高亚型选择性抑制剂包括BD1、BD2以及BRD4选择性抑制剂等。 Pelabresib就是在泛BET抑制剂JQ1的基础上进行优化改造而得。化合物JQ1是一种研发较早的BET小分子抑制剂，其作用疾病范围广泛，但是半衰期短且治疗过程中毒性较大，为了得到药效持久且毒性较低的高选择性BET抑制剂，Pelabresib在JQ1的基础上，用苯环替换代谢不稳定的噻吩环改造而来，它对BD1的抑制活性是BD2的6倍以上。在治疗骨髓纤维化患者的II期临床试验中，Pelabresib表现出积极的疗效，其与JAK抑制剂ruxolitinib联用，在未接受过JAK抑制剂治疗的患者中能够让67%的患者脾脏体积缩小35%以上。目前全球III期临床研究正在进行中。目前，多款高选择性BET抑制剂正在研发中。如GSK的BD1选择性抑制剂GSK779、艾伯维的BD2选择性抑制剂ABBV-744、以及靶向BRD4的PROTACs等。在国内，也有多家企业在进行相关产品的研发，如贝达药业的BET抑制剂BPI-23314，其能抑制BET相关多种癌症基因表达及降解靶蛋白BRD4等；文达医药的NHWD-870 HCl，是一款靶向BRD4的选择性抑制剂，拟开发用于治疗晚期复发非霍奇金淋巴瘤、非小细胞肺癌和小细胞肺癌等；加科思的BET抑制剂JAB-8263，临床前研究表明其对多种实体瘤和血液瘤均能发挥抗肿瘤作用。总之，BET抑制剂赛道已变得非常拥挤，不过以上BET抑制剂大多处于临床早期阶段。MorphoSys AG的Pelabresib是为数不多进入临床III期的高选择性BET抑制剂，未来有望率先撞线，是一款潜在FIC的骨髓纤维化疗法。 EZH2抑制剂CPI-0209 EZH2是一种组蛋白赖氨酸甲基转移酶，其通过催化组蛋白H3赖氨酸27（H3K27）的甲基化以控制各种基因表达，从而调节细胞的正常生理功能。在多种癌症中均存在EZH2的失调，另外EZH2的表达还与临床的不良预后和疗效相关。自EZH2在临床上发现其与肿瘤的发生及预后相关后，科学家们就尝试利用EZH2抑制剂来干预肿瘤发生的甲基化水平。2012年开始，Epizyme、诺华、GSK、辉瑞、第一三共等陆续入局EZH2抑制剂的研发。 MorphoSys AG的CPI-0209是一款新一代EZH2抑制剂，临床前研究显示，CPI-0209具有比其他EZH2抑制剂强10-500倍的效力，目前，它正在开展I/II期临床试验，治疗多种血液瘤和实体瘤患者。目前，大多EZH2抑制剂仍处于临床开发的前期，很多临床试验正在摸索中前进，尚未形成同质化恶性竞争，MorphoSys AG的CPI-0209尚有突围机会。上述三款产品是目前MorphoSys AG仅剩的三款产品，从分析可知，三款产品各有优势，且在研产品在领域内研发进度均靠前，未来很有希望分到市场的一杯羹。事实上，在资本寒冬下，缩减管线，及时调整研发策略是再正常不过的一件事，就连大厂也在不断瘦身，如辉瑞在2022年财报披露中曾透露，公司将剔除8个研发项目；BMS也在2022年财报中表示将削减9项资产；国内三叶草生物也在去年年中对外宣布，将优先把所有资源配置给新冠疫苗这一管线，减少非新冠项目的投入。如今，MorphoSys AG由于市场变化，欲将有限的资源集中到更具希望的临床后期管线项目上，虽然砍掉临床前团队这一决策的影响要在多年后才会得到验证，但就当下来说，这一决策不失为明智之举。毕竟，在资本寒冬下，如何活下去，活得好，才是当下创新biotech要思考的第一要义。参考来源： 1. https://www.morphosys.com/media-investors/media-center/fda-approves-monjuvir-tafasitamab-cxix-in-combination-with-lenalidomide; 2. Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study [published online ahead of print, 2020 Jun 5]. Lancet Oncol. 2020;S1470-2045(20)30225-4. doi:10.1016/S1470-2045(20)30225-4; 3. Pan Tang,Jifa Zhang et al.（2021）. Targeting Bromodomain and Extraterminal Proteins for Drug Discovery: From Current Progress to Technological Development.Journal of Medicinal Chemistry,DOI: 10.1021/acs.jmedchem.0c01487； 4. 陈金晶，赵晓丽等.（2017）.含溴结构域和额外终端域家族蛋白--表观遗传领域的新型治疗靶点。《药学学报》DOI：：10.16438/j.05l3-4870.2017-0143； 5. 宫玉芳等. 新兴抗肿瘤靶点EZH2作用机制及研究进展.《现代肿瘤医学》，2020, 28（10）, 1757-1760. 智药研习社近期研习会报名来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

免疫疗法加速审批临床3期临床2期细胞疗法

100 项与 NHWD-870 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床2期	中国	浙江文达医药科技有限公司	2024-04-25
晚期 NUT 癌	临床2期	中国	浙江文达医药科技有限公司	2024-04-25
弥漫性大B细胞淋巴瘤	临床2期	中国	浙江文达医药科技有限公司	2023-10-26
非霍奇金淋巴瘤	临床2期	-	浙江文达医药科技有限公司	-
NUT中线癌	临床2期	-	浙江文达医药科技有限公司	-
难治性弥漫性大 B 细胞淋巴瘤	临床1期	中国	浙江文达医药科技有限公司	2021-01-29
播散性弥漫性大 B 细胞淋巴瘤	临床1期	中国	浙江文达医药科技有限公司	2021-01-29
滤泡性淋巴瘤	临床1期	中国	浙江文达医药科技有限公司	2021-01-29
皮肤黑色素瘤	临床1期	中国	浙江文达医药科技有限公司	2021-01-29
黏膜黑色素瘤	临床1期	中国	浙江文达医药科技有限公司	2021-01-29

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临床结果

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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


NHWD-870 (WCLC2017)	N/A	小细胞肺癌	-	NHWD-870	鹽糧獵觸鑰夢膚願艱願(製顧獵壓膚鏇糧糧鏇鏇) = 鹹齋簾鏇遞顧選顧構窪廠膚蓋鹽遞築簾糧簾壓 (糧選鏇窪鬱襯醖積夢鹹 )	-	2017-10-17