药物发现

天境生物的创新引擎由一群具有深厚学术功底和丰富行业经验的免疫学家们驱动。我们的药物发现团队在靶标选择和免疫学方面有着丰富的研发经验,能够鉴别,发现并且将创新或差异化的科学假设转化为候选分子。 在短短的四年内,我们已经开发了一系列全新或高度差异化的药物分子。其中有三种单克隆抗体在美国和中国进入了临床研究阶段。


聚焦靶点生物学开发创新或差异化药物分子

我们聚焦肿瘤免疫和自身免疫两大治疗领域,在发现和鉴定药物靶点及其免疫学原理方面拥有自己独特的优势。我们的早期药物分子研究团队在T细胞、B细胞和巨噬细胞等多种免疫细胞功能分析方面拥有深厚的研究经验及科研积累。通过设计高通量和高质量的筛选平台,我们可以显著提高药物筛选效率以及发现正确分子的概率。

我们的早期研发团队热衷并擅长于开发具有临床意义的创新单克隆抗体,以及具有协同生物学特性的全新或高度差异化的双功能分子。立足差异化开发策略,通过一系列体内体外筛选实验,我们得到了具有差异化优势的TJC4和TJD5分子。

公司研发团队在CD47抗体开发伊始便设计了筛选不结合红细胞CD47抗体的开发策略以及相应的开发方案,并最终获得了具有差异化优势的CD47抗体TJC4。TJC4具有独特的CD47识别表位,该表位在红细胞上被遮蔽,不能被TJC4识别。因此,TJC4不会引起血液学上的副作用。TJC4差异化的作用机制已在一系列体外实验和多次猴子实验中得到验证,目前在美国处于I期临床阶段。

我们研发能力还体现于最新研发的一组新型双特异性抗体,这代表了新一波肿瘤药物候选分子。这类双特异性抗体具有新颖的生物学特性,能够通过双重靶向PD-L1来富集肿瘤中的免疫细胞,并激活免疫细胞以产生协同抗肿瘤作用。这些双特异性候选分子已显示出独特的特性,对肿瘤的反应更加灵敏。例如,针对CD47抗体单用可能无效的实体瘤或对标准PD-1和PD-L1治疗应答不佳的肿瘤,我们分别创建了全新的双功能分子TJ-C4GM和TJ-L1I7。

基于高效的免疫细胞功能筛选平台,依托定制化的抗体工程技术,我们致力于开发最具创新力的药物。

技术平台

采用定制化蛋白工程平台研发新分子

通过四大抗体工程平台,设计具有特定生物学特性的药物分子,赋予双特异性抗体明确的生物学特性,并保持分子的工艺性和成药性。迄今为止,我们已经创建了七个新的临床前阶段双特异性药物分子。


不同的分子搭配需要不同的技术平台以实现特定的生物学特性。因此,除了我们自己的Ig-scFv双特异性抗体平台BIMAB外,我们还与ABL Bio和WuXi Biologics合作共享其抗体工程平台,提高双抗成药的成功率。我们专有的抗体细胞因子技术能把作用于肿瘤的抗体与调节免疫功能的细胞因子联系起来,制备出另一种形式的双特异性抗体如TJ-L1I7和TJ-C4GM。

  • 抗体细胞因子

  • 双特异抗体

  • 长效hyFc TM蛋白

  • 单克隆抗体

发表文献

自主研发的单克隆抗体

  • αCD47
    (TJC4)

    A differentiated CD47 therapeutic antibody recognizing a novel epitope and sparing erythrocytes and platelets

    Poster presentation at the 2017 EACR meeting

    Tumor cells overexpress CD47 which engages signal-regulatory protein (SIRPa) on macrophages (mf) to deliver a “do-not-eat” signal to avoid being phagocytosed.

  •   

    TJC4, A Differentiated RBC Sparing Anti-CD47 Antibody for Anti-Cancer Therapy

    Poster presentation at the 2019 ASH meeting

    I-Mab has developed a novel CD47 antibody, TJC4 also known as TJ011133, which was endowed with an RBC sparing property and unique binding epitope, may have better safety profile based on the pre-clinical data.

  •   

    A first-in-patient study of lemzoparlimab, a differentiated anti-CD47 antibody, in subjects with relapsed/refractory malignancy: initial monotherapy results

    Poster presentation at the 2020 SITC Meeting

    CD47 blockade using SIRPα-Fc or anti-CD47 antibodies results in inhibition of the ‘do not eat’ signal and activation of phagocytosis and has emerged as a promising cancer treatment strategy. However, targeting CD47 leads to various hematological toxicities, particularly anemia and thrombocytopenia. Lemzoparlimab (also known as TJ011133 or TJC4) is a fully human, anti-CD47 IgG4 antibody that is endowed with a red blood cell (RBC) sparing property and unique binding epitope, potentially differentiating itself from other CD47 axis targeting therapies.

  • αLAG3

    Discovery of a novel anti-LAG3 antagonist antibody

    Poster presentation at the 2018 SITC meeting

    LAG3 is a negative regulator of T cells. Persistent T-cell activation in a chronic inflammatory environment, as in a tumor or during chronic viral infection, results in sustained LAG3 expression, contributing to a state of exhaustion manifest in impaired proliferation and cytokine production.

  • αTIGIT

    Discovery of a novel TIGIT therapeutic antibody with strong efficacy in tumor xenografts as monotherapy

    Poster presentation at the 2018 SITC meeting

    The immune checkpoint co-inhibitory receptor TIGIT (T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif) is expressed on activated CD4+ T, CD8+ T and NK cells and on regulatory T cells (Tregs). Blocking TIGIT interaction with its ligand CD155 can re-energize tumor antigen-specific CD8+ T cells, unleash NK cells and inhibit Treg-mediated immunosuppression in the tumor microenvironment.

自主研发的免疫细胞因子

  • αCD47-
    GMCSF
    (TJC4GM)

    A novel immunocytokine fusion protein combining tumor-targeting anti-CD47 antibody with GM-CSF cytokine for enhanced anti-tumor efficacy

    Poster presentation at the 2018 AACR meeting

    CD47 blockade has emerged as a promising cancer immunotherapy by promoting phagocytosis of tumor cells. However, this treatment strategy may be limited by the predominant accumulation of macrophages with pro-tumor M2 phenotype.

  • αPDL1-IL7
    (TJL1I7)

    A novel anti-tumor anti-PDL1-IL7 immunocytokine targeting lymphocytes

    Poster presentation at the 2019 SITC meeting

    Lymphocyte counts in the peripheral immune system and tumor are correlated with positive clinical outcomes in PD-(L)1 immunotherapy. Interleukin7 (IL7) is an immune homeostasis cytokine for T cells.

临床项目及进展

  • IL7-hyFc
    (TJ107)

    A Phase I/IIa, Open-label, Dose-Escalation and Dose Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TJ107 in Chinese Patients with Advanced Solid Tumors

    Poster presentation at the 2019 SITC meeting

    TJ107, an immuno-oncology agent also known as Hyleukin, is a T cell amplifier comprising a homodimer of engineered human interleukin-7 (IL-7) fused with Genexine’s proprietary long-acting platform hybrid Fc. IL-7 is a critical homeostatic factor for T cells, acting on T cells to increase their number, diversity and functionality.

自主研发的双特异性抗体

  • αCLDN18.2-4-1BB
    (TJCD4B)

    Claudin 18.2 - 4-1BB bispecific antibody induced potent tumor inhibition through tumor-specific 4-1BB activation

    Poster presentation at the 2020 AACR meeting

    Claudin 18.2 (CLDN18.2) is a gastric-specific membrane protein, and is believed to be an ideal tumor antigen for immunotherapy. I-Mab and ABL Bio co-develop a bispecific antibody CLDN18.2-4-1BB (TJCD4B). TJCD4B showed strong tumor growth inhibition (TGI) of CLDN18.2 expressing tumor cells, with an increase of tumor infiltrating lymphocytes. Our data suggested TJCD4B activated 4-1BB in a CLDN18.2-dependent manner, thus addressing the safety concern associated with 4-1BB-based therapies. TJCD4B is a promising IO therapeutic option for gastric and other CLDN18.2-positive tumors.

 

知识产权

天境生物十分重视知识产权保护和侵权风险防控,通过自主研发和项目引进不断加强我们的知识产权,为候选药物的开发和未来的商业化保驾护航。在外部和内部IP律师的共同努力下,我们逐渐建立起一套行之有效的IP管理系统,不仅涉及专利保护和商业秘密管理,而且注重IP的组合管理。

截至2020年12月31日,天境生物自主研发且具有全球知识产权的候选药物已获得270多件授权专利/专利申请,包括TJC4、TJD5、TJX7、TJ-CD4B等,主要涉及美国、欧洲、韩国、日本、俄罗斯、印度、澳大利亚等国家;引进产品包括TJ202、TJ101、TJ301、TJ271和TJ107,天境生物就引进产品在大中华区获得的超过50件专利/专利申请享有独家许可权。

 

 

 

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