Discovery Research

Our innovative discovery engine is built around the world-class expertise of a group of seasoned immunologists with extensive academic research and drug R&D experience. Our discovery team possesses world-class expertise in cutting-edge target biology and immunology to identify, create and translate science into “points of innovation” or differentiation to develop novel molecules. In a short span of four years, we have generated a panel of novel or highly differentiated drug molecules. Three of our monoclonal antibodies have entered clinical studies in the US.


Target Biology to Create Novel or Highly Differentiated Molecules

Our world-class expertise in immunology drives the identification of biological targets, and their immunological mechanisms of action, across the two therapeutic areas we focus on. Our discovery team has deep expertise in functional assays across a wide range of immune cells, including T cells, B cells and macrophages. By designing robust, high-throughput assays, we significantly increase screening efficiency and the probability of finding differentiated molecules.

Our discovery team is passionate about, and has excelled in, developing novel monoclonal antibodies by creating clinically meaningful differentiated, as well as novel or highly differentiated, bi-functional molecules that synergize biologic properties. For example, the demonstrated differentiation of TJC4 and TJD5 was engineered by design from an antibody screen through stepwise in vitro and in vivo validation processes. 

Instead of performing routine or traditional antibody screening, we set a specific goal to identify and select a unique CD47 antibody that is free from binding to red blood cells (RBC) among all CD47 antibody leads that naturally bind to RBCs. As a result, we selected, by design, our proprietary CD47 antibody (TJC4), with a rare epitope, uniquely spares binding to RBCs, which differentiates it from other CD47 antibodies that typically cause hematologic side effects. TJC4 has been validated in a series of in vitro assays as well as multiple monkey studies for its unique differentiation and is in a Phase 1 clinical trial in the US.

Another example of our R&D capability relates to our novel bi-specific antibody panel that represents a new wave of oncology drug candidates. We have created novel bi-specific antibodies with novel biological properties that are capable of enriching immune cells in tumors through dual targeting of PD-L1 and activating immune cells for a synergistic anti-tumor effect. These bi-specific drug candidates have been shown to exhibit unique properties that render tumors more responsive to treatment. TJ-C4GM and TJ-L1I7, for example, were designed as bi-functional molecules to specifically treat solid tumors that otherwise may not respond to the CD47 antibody alone, or tumors that respond poorly to standard PD-1 and PD-L1 treatment, respectively.

This discovery expertise, combined with our ‘fit-for-purpose’ antibody-engineering technology platforms as described below, fuels a powerful engine of innovation to create novel or highly differentiated molecules.

Technology platforms

Fit-for-Purpose Technology to Create Novel Molecules

We utilize four antibody or molecular engineering platforms in our ‘fit-for-purpose toolbox’ to engineer drug molecules that capture defined biologic properties of bi-specific antibodies and retain good manufacturability and druggability of the molecules. To date, we have created seven novel preclinical stage bi-specific drug molecules.

In addition to our own Ig-scFv bi-specific antibody platform, we have partnered with ABL Bio and WuXi Biologics to access their antibody engineering platforms in order to increase the probability of success, as different molecular configurations require different technologies. Furthermore, our proprietary antibody-cytokine technology has enabled another form of bi-specific antibodies, such as TJ-L1I7 and TJ-C4GM, that link a tumor-engaging antibody with an immuno-modulatory cytokine. 

  • Ig-cytokine

  • Bi-specific

  • Hy-Fc Protein

  • Monoclonal

Publications and Presentations

Our Proprietary Therapeutic Monoclonal Antibodies

  • 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 Anti-CD47 Antibody with Novel Epitope and RBC Sparing Properties

    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.

  • 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.

Our Proprietary Immunocytokines

  • 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.

Our Clinical Programs – Clinical Trial Progress

  • 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.

Intellectual Property

We seek to strengthen our intellectual property (IP) portfolio continuously through in-house R&D and in-licensing. To maintain our competitive advantage, we strive to safeguard our proprietary technology and drug candidates. With the help of our US and China IP counsels, we are establishing an efficient IP management system for patent filing, portfolio management, and confidentiality management.

As of October 30,2019, our patent portfolio consists of more than 170 issued patents and patent applications primarily related to the drug candidates in our Global Portfolio. Meanwhile, we have in-licensed the Greater China rights of 43 issued patents and patent applications primarily involving TJ202, TJ101, TJ301, TJ271 (Enoblituzumab) and TJ107. We also have 21 registered trademarks and trademark applications as of October 2019.

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