更新于：2024-11-01

MSLN x CD47

更新于：2024-11-01

基本信息

关联

项与 MSLN x CD47 相关的药物

NI-1801

靶点

CD47 x MSLN

作用机制

CD47抑制剂 [+1]

在研机构

Novimmune SA

原研机构

Novimmune SA

在研适应症

Mesothelin阳性实体瘤 [+1]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 MSLN x CD47 相关的临床试验

NCT05403554 / Recruiting临床1期

A Phase 1, Open-Label, Dose Finding Study of NI-1801, a Bispecific Mesothelin X CD47 Engaging Antibody, As a Single Agent, in Combination with Anti-PD-1 Antibody, and in Combination with Weekly Paclitaxel (Standard of Care) in Patients with Mesothelin Expressing Ovarian, Pancreatic, Non-Small-Cell-Lung and Triple-Negative Breast Cancers

Study LCB-1801-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), first-in-human clinical study of NI-1801 in patients with advanced, metastatic, or recurrent solid malignancies expressing mesothelin (MSLN).
The dose escalation part (Part A) of the main study will evaluate the safety and tolerability of escalating doses of NI-1801 to determine the maximum tolerated dose (MTD) and non-tolerated toxic dose (NTD) of NI-1801. The expansion part (Part B) of the main study will further evaluate the safety and efficacy of NI-1801 administered at or below the MTD in up to 10 additional subjects in order to determine the recommended Phase 2 dose (RP2D).
Treatments will be administered in 28-day cycles for up to 12 months until disease progression, unacceptable toxicity, or Investigator/patient decision to withdraw study consent.
The dose escalation part (Part A) of the sub-study will evaluate the safety and tolerability of escalating doses of NI-1801 in combination with anti-PD-1 antibody. The expansion part (Part B) of the sub-study will further evaluate the safety and efficacy of NI-1801 administered in combination with anti-PD-1 antibody at or below the MTD.
In the randomized cohort, the experimental arm will receive the investigational drug NI-1801 at the P2RD every two weeks in combination with weekly administration of paclitaxel (80 mg/m^2) over 4-week cycles. The control arm will be treated with weekly paclitaxel at the same regimen representing one of the standards of care (SoC) in this population. This trial specifically targets patients with platinum-resistant ovarian cancer. This cohort will be made up of 20 evaluable patients, 10 per arm.

开始日期2022-04-29

申办/合作机构

Novimmune SA

100 项与 MSLN x CD47 相关的临床结果

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100 项与 MSLN x CD47 相关的转化医学

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0 项与 MSLN x CD47 相关的专利（医药）

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项与 MSLN x CD47 相关的文献（医药）

2020-01-01·mAbs2区 · 医学

Targeting a membrane-proximal epitope on mesothelin increases the tumoricidal activity of a bispecific antibody blocking CD47 on mesothelin-positive tumors

2区 · 医学

Article

作者: Pontini, Guillemette ; Calloud, Sebastien ; Masternak, Krzysztof ; Charreton, Maud ; Juan, Flora ; Chatel, Laurence ; Chauchet, Xavier ; Shang, Limin ; Hatterer, Eric ; Richard, Françoise ; Moine, Valéry ; Barba, Leticia ; Bautzova, Tereza ; Broyer, Lucile ; Buatois, Vanessa ; Bosson, Nicolas

Mesothelin (MSLN) is a cell surface glycoprotein overexpressed in several solid malignancies, including gastric, lung, mesothelioma, pancreatic and ovarian cancers. While several MSLN-targeting therapeutic approaches are in development, only limited efficacy has been achieved in patients. A potential shortcoming of several described antibody-based approaches is that they target the membrane distal region of MSLN and, additionally, are known to be handicapped by the high levels of circulating soluble MSLN in patients. We show here, using monoclonal antibodies (mAbs) targeting different MSLN-spanning epitopes, that the membrane-proximal region resulted in more efficient killing of MSLN-positive tumor cells in antibody-dependent cell-mediated cytotoxicity (ADCC) assays. Surprisingly, no augmented killing was observed in antibody-dependent cellular phagocytosis (ADCP) by mAbs targeting this membrane-proximal region. To further increase the ADCP potential, we, therefore, generated bispecific antibodies (bsAbs) coupling a high-affinity MSLN binding arm to a blocking CD47 arm. Here, targeting the membrane-proximal domain of MSLN demonstrated enhanced ADCP activity compared to membrane-distal domains when the bsAbs were used in in vitro phagocytosis killing assays. Importantly, the superior anti-tumor activity was also translated in xenograft tumor models. Furthermore, we show that the bsAb approach targeting the membrane-proximal epitope of MSLN optimized ADCC activity by augmenting FcγR-IIIA activation and enhanced ADCP via a more efficient blockade of the CD47/SIRPα axis.

2019-12-01·Journal of Hematology & Oncology

CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy

作者: Liu, Delong

AbstractNew advances in the design and manufacture of monoclonal antibodies, bispecific T cell engagers, and antibody-drug conjugates make the antibody-directed agents more powerful with less toxicities. Small molecule inhibitors are routinely used now as oral targeted agents for multiple cancers. The discoveries of PD1 and PD-L1 as negative immune checkpoints for T cells have led to the revolution of modern cancer immunotherapy. Multiple agents targeting PD1, PD-L1, or CTLA-4 are widely applied as immune checkpoint inhibitors (ICIs) which alleviate the suppression of immune regulatory machineries and lead to immunoablation of once highly refractory cancers such as stage IV lung cancer. Tisagenlecleucel and axicabtagene ciloleucel are the two approved CD19-targeted chimeric antigen receptor (CAR) T cell products. Several CAR-T cell platforms targeting B cell maturation antigen (BCMA) are under active clinical trials for refractory and/or relapsed multiple myeloma. Still more targets such as CLL-1, EGFR, NKG2D and mesothelin are being directed in CAR-T cell trials for leukemia and solid tumors. Increasing numbers of novel agents are being studied to target cancer-intrinsic oncogenic pathways as well as immune checkpoints. One such an example is targeting CD47 on macrophages which represents a “do-not-eat-me” immune checkpoint. Fueling the current excitement of cancer medicine includes also TCR- T cells, TCR-like antibodies, cancer vaccines and oncolytic viruses.

2019-10-01·Antibody Therapeutics

Highlights of 2019 Protein Engineering Summit (PEGS) in Boston, USA: advancing antibody-based cancer therapies to the clinic

Article

作者: Wang, Cheng ; Wang, Shouye ; Li, Hong ; Li, You ; Ho, Mitchell

AbstractThe 15th Annual Protein Engineering Summit (PEGS) organized by Cambridge Healthtech Institute was held in Boston, USA, from 8 to 12 April 2019. This report highlights the presentations in the Oncology Stream of this meeting with a focus on bispecific antibodies (BsAbs). A variety of BsAb formats with different target antigens (CD3, CTLA4, PD-1, PD-L1, EGFR, HER2, BCMA, CD19, CD20, CD38, CD123, TGFβ, PSMA, etc.) have been discussed, in which the T-cell engaging (anti-CD3) BsAb is the most studied construct to exhibit promising immunotherapeutic activities. The BsAb formats include IgG-like structures or antibody fragments composed of antigen-binding sites only. Preclinical and clinical data from different BsAbs demonstrated the potential therapeutic applications in various solid tumors and hematological malignancies. The ongoing development of BsAb formats will help overcome current clinical issues, such as tumor selectivity and antigen coverage. This report also covers several presentations about emerging targets (e.g. mesothelin, CD47) and new technologies in the field of antibody engineering and therapeutics.

项与 MSLN x CD47 相关的新闻（医药）

2024-09-04

·Armstrong生物药资讯

实体瘤CAR-T明星：Arsenal Bio完成3.25亿美元C轮融资

▎Armstrong 2024年9月4日，Arsenal Biosciences宣布完成3.25亿美元C轮融资，新投资机构包括ARCH Venture Partners、Milky Way Investments Group、再生元、英伟达风投基金、Luma Group，老投资人软银愿景基金二期、BMS、Westlake Village BioPartners、PICI、Kleiner Perkins、Byers Capial、Hitachi Ventures追加投资。 Arsenal Biosciences聚焦研发实体瘤CAR-T疗法，首发管线AB-1015用于治疗卵巢癌，已经进入临床阶段。 Arsenal Bio成立于2019年，当年完成8500万美元A轮融资，2022年完成2.2亿美元B轮融资，此次完成3.25亿美元C轮融资，累计融资金额达到6.3亿美元。Arsenal Bio的联合创始人Ken Drazan曾是一名肝移植外科医生，后从事风险投资。另一位联合创始人W.Nicholas Haining曾是默克研究实验室的发现肿瘤学和免疫学副总裁。 Arsenal Bio尝试通过多种技术手段来让CAR-T攻克实体瘤。 Arsenal采用CITE技术实现单点定点插入，而不是随机多点插入。 Arsenal Bio采用多个模块来改造CAR-T，包括精准插入、逻辑门、克服肿瘤微环境免疫抑制性等。 Logic gate的目的是让CAR-T在健康细胞中不会被激活，只有结合肿瘤细胞才会激活，具体而言是两个癌细胞同时表达的靶蛋白结合后才会激活。以首发管线AB-1015为例，靶向MSLN治疗卵巢癌，同时ALPG靶向用来实现肿瘤细胞特异性的激活，FAS shRNA用来规避TME的抑制性，PTPN2 shRNA用来优化CAR-T的杀伤效应。总结 CAR-T在血液瘤取得了很多突破，但实体瘤一直进展不大。Arsenal Biosciences针对这一问题，围绕CAR-T进行了系统化的工程化改造设计，与传统CAR-T有着非常大的不同。这些尝试也得到了众多基金包括MNC的认可，BMS、再生元等纷纷选择投资或合作。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇； CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

细胞疗法免疫疗法抗体药物偶联物

2024-08-19

·Armstrong生物药资讯

宜联生物：FDA解除HER3 ADC临床的部分暂停

▎Armstrong 2024年8月19日，宜联生物宣布FDA正式解除了对HER3 ADC新药YL202一期临床试验的部分暂停，该临床试验将继续患者入组，并将集中在3.0mg/kg及以下剂量水平进行开发。今年ASCO会议上，YL202报告了一期临床最新数据，一期临床原计划剂量爬坡从0.5mg/kg到5.5mg/kg。可以看到DL1-4也就是3.0mg/kg及以下剂量的耐受性较好。可以看到剔除4.0mg/kg、4.5mg/kg、5.5mg/kg剂量组，YL202的有效性仍然非常好。总结宜联生物基于TMALIN技术平台开发了多款创新ADC管线，同时也达成多项授权合作或共同开发合作，包括授权给BioNTech的HER3 ADC，授权给罗氏的cMET ADC，与复宏汉霖进行技术授权开发的PD-L1 ADC、EGFR ADC，与再鼎医药进行技术授权开发的DLL3 ADC，与和铂医药进行技术授权开发的MSLN ADC等。虽然HER3 ADC一期临床爬坡方案有些激进，但3.0mg/kg及以下剂量已经表现出优异的疗效，同时安全性可控，期待其后续临床进展。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇； CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

抗体药物偶联物临床1期ASCO会议临床结果

2024-06-21

·医药笔记

365例：辉瑞/诺纳生物MSLN ADC启动美国一期临床

▎Armstrong 2024年6月19日，Seagen在Clinicaltrials.gov网站上注册了SGN-MesoC2的一期临床试验，用于治疗晚期实体瘤患者。该一期临床试验计划入组365例晚期实体瘤患者，预计2028年11月完成。探索的瘤种包括非小细胞肺癌、卵巢癌、胰腺癌、间皮瘤、结直肠癌等。 SGN-MesoC2即Seagen于2023年12月从和铂医药子公司诺纳生物引进的MSLN ADC，Seagen支付预付款及近期付款5300万美元、潜在里程碑付款或高达约10.5亿美元，以及按净销售额支付的分级特许权使用费，其最高比例可达高双位数。 HBM9033进行了充分的差异化设计，抗体部分与可溶性MSLN结合较弱，与膜上MSLN亲和力高，从而减少血液中可溶MSLN带来的影响。合理调节的结合动力学指标，选择具有更高Koff的抗体，用以提高肿瘤内部的穿透性。同时，HBM9033采用第四代双机制肿瘤特异性解离接头，并配合活性更优的新一代拓扑异构酶抑制剂。HBM9033在体内研究中表现出卓越的药效性和安全性，尤其对于抗原表达异质性的肿瘤，小鼠模型中其治疗效果远远高于目前的临床阶段竞品。总结诺纳生物一方面与众多ADC明星公司达成合作，共同开发新一代ADC药物，另一方面也在积极开发双特异性ADC或者双表位ADC的研究。此外，公司并未局限于ADC本身，也在探索抗体偶联核素等更广泛的生物偶联药物领域。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇； CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

抗体药物偶联物引进/卖出临床2期临床1期