11亿美元合作,赛诺菲与Biond共同开发新的肿瘤免疫治疗新靶点----ILT2抗体抑制剂BND-22

2021-01-16 网络 网络

2021年1月13日,以色列创新生物药公司Biond Biologics宣布,与赛诺菲公司签订了一份价值11亿美元的全球许可协议,协议核心产品为首个(first-in-class)人源化IgG4抗IL

2021年1月13日,以色列创新生物药公司Biond Biologics宣布,与赛诺菲公司签订了一份价值11亿美元的全球许可协议,协议核心产品为首个(first-in-class)人源化IgG4抗ILT2单克隆抗体,可同时作用于巨噬细胞、NK细胞和T细胞,将开发治疗实体肿瘤, 预计到2021年中期进入I期临床阶段。

BND-22是一种人源化的IgG4,靶向免疫球蛋白样转录子2(ILT2)受体的抗体拮抗剂,可用于治疗实体瘤。ILT2是ILT免疫调节受体家族成员之一,是一种在先天和适应性免疫细胞上表达的抑制性受体,它与包括HLA-G在内的MHC I类分子结合,HLA-G是一种由多种肿瘤类型表达的免疫抑制蛋白。

根据该协议的条款,Biond将获得1.25亿美元的现金预付款,并有权获得超过10亿美元的开发,监管和销售里程碑付款,以及两位数的分层特许权使用费。而在具体实施过程中,Biond将领导BND-22的Ia临床阶段研究,以评估BND-22作为单一药物的安全性和耐受性,以及与已批准的癌症治疗药物联合使用,并探索BND-22抗肿瘤活性与选定肿瘤和血液生物标志物之间的潜在联系。此后,赛诺菲将承担临床开发和商业化的责任。

此前的临床前研究表明,BND-22通过靶向巨噬细胞中的ILT2介导的“不要吃我”信号,激活自然杀伤细胞(NK)和CD8+淋巴细胞,具有广泛的抗肿瘤作用。BND-22的研究新药(IND)申请最近已提交给FDA,并计划于2021年年中开始一期研究,以评估BND-22在晚期癌症患者中的安全性、耐受性和初步抗肿瘤活性。

ILT2是一种多类型细胞抑制性免疫检查点,在先天性免疫细胞(巨噬细胞、NK细胞)和适应性免疫细胞(T细胞)上均有表达。ILT2与MHCⅠ类分子如HLA-G紧密结合,HLA-G是一种在多种类型肿瘤表明表达的免疫抑制分子。

ILT2介导的免疫抑制可导致T细胞和NK细胞的细胞毒性和增殖受损,并产生一个“不要吃我”的信号,从而阻止巨噬细胞有效吞噬肿瘤细胞,故可将ILT2信号确定为抗癌免疫治疗的潜在新靶点。

BND-22对ILT2具有较高的亲和力和选择性。BND-22可阻断ILT2-HLA-G相互作用。BND-22阻断ILT2可增强巨噬细胞对肿瘤细胞的吞噬作用,增强T细胞和NK细胞对多种癌细胞杀伤力。

到目前为止,癌症免疫疗法的发展重点一直放在刺激适应性免疫系统攻击恶性细胞,特别是T淋巴细胞的药物上。不过,该策略的缺陷是许多晚期癌症患者并未从这些药物中获得持久的受益。而BND-22作为一种新型的免疫疗法,既针对适应性免疫细胞,又针对先天性免疫细胞,并且不仅利用T细胞,还将利用其他免疫细胞(如NK细胞)和巨噬细胞的抗肿瘤活性。

Biond Biologics是一家药物发现和开发公司,致力于通过发现免疫调节途径并实现生物制剂的细胞内递送,为新型肿瘤学目标开发创新疗法。Biond的产品线基于对新发现的免疫检查点和免疫逃逸机制的内部研究,领先的开发计划包括BND-22(一种靶向ILT2的多细胞检查点抑制剂)和BION-206(一种通过靶向可溶性CD28克服PD-1阻断耐药性的新型药物)。

除了其免疫治疗药物的生产线外,Biond还开发了INspire,这是一个创新的技术平台,能够将生物制剂在细胞内传递到细胞内。INspire基于化学修饰的载体蛋白,该蛋白可与蛋白质治疗剂(例如抗体或酶)偶联,设计用于在细胞内提供偶联治疗,从而提供许多目前认为“不可用药”的关键疾病靶点。

参考来源:

Biond Biologics and Sanofi Enter into Global Licensing Agreement for BND-22, a Novel Immune Checkpoint Inhibitor Targeting the ILT2 Receptor

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    2021-06-10 sunylz
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    2021-03-20 jklm09
  3. 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    2021-01-19 水晶8077

    厉害了

    0

  4. 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    2021-01-18 lsndxfj
  5. 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createdBy=35645453396, createdName=ms2000001516371729, createdTime=Sat Jan 16 22:41:58 CST 2021, time=2021-01-16, status=1, ipAttribution=)]
  6. 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  7. 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    2021-01-17 841975707

    真牛

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  8. 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    2021-01-17 841975707

    真牛

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  9. 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    2021-01-16 ms9000000657906932

    厉害

    0

  10. 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    2021-01-16 ms2000001516371729

    0

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