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Anti-Her2 II / Anti-Her2 IV Bi-specific antibody ADC

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  • Project profile
    Project name: Anti-Her2 II / Anti-Her2 IV Bi-specific antibody ADC
    Indications: Solid tumor
    Research phase: Preclinical
    Cooperation demands: License-out or co-development
  • Highlights

    1. Clear MoA:

    Clear MoA

    (1) Antibody-drug conjugates (ADCs) are a rapidly growing class of cancer therapeutics that seek to overcome the low therapeutic index of conventional cytotoxic agents. However, realizing this goal has been a significant challenge. ADCs comprise several independently modifiable components, including the antibody, payload, linker, and bioconjugation method. Many approaches have been developed to improve the physical properties, potency, and selectivity of ADCs.

    (2) ADC stands for antibody-coupled drug, which is formed by coupling a monoclonal antibody with a small molecule drug. This drug has the characteristics of high specificity and good safety, which can effectively kill tumor cells and be used in the clinical treatment of tumor diseases. The mechanism of action of ADC drugs is mainly through the targeting effect of monoclonal antibodies to specifically recognize the antigens on the surface of tumor cells, and then the endocytosis of the cells in the patient's body can make the chemical drugs enter the tumor cells in the patient to achieve the purpose of killing the tumor cells in the body. Since the small-molecule drugs of ADC drugs are generally released after they enter tumor cells, the safety of ADC drugs can be improved, the side effects of drugs can be reduced, and the effectiveness of drugs can be enhanced.

    (3) This molecule is the first reported P-BsADC that introduce bispecific antibody as its component and used PEG as its framework.

    2. Excellent molecular design:

    (1) Site-specific conjugation to reduce mismatch rate of bispecific antibody and control drug-to-antibody ratios (DAR) precisely, resulting in homogenous and stable end-product. Moreover, simple organic synthesis could scale up easily.

    (2) No Fc/FcR mediated non-target toxicity effect, by substituting Fc fragment with PEG.

    3. Excellent preclinical result:

    (1) Low binding-site barrier due to small molecular weight compared to marketed ADC, high efficiency of endocytosis with low excretion results in high utilization ratio of the drug, make this P-BsADC a promising candidate for the treatment of solid tumor.

    Clear MoA

    (2) Excellent bystander effect compared with DS8201 and T-DM1 in cells.

    (3) Tumor inhibiting ability was better than T-DM1 and DS8201a in both HER2 high and low expression models at the same dose. (Breast cancer, pancreatic cancer)

    Clear MoA

    Clear MoA

    Clear MoA

    (4) Without Fc, no cytotoxicity to megakaryocytes was observed, its huge improvement over DS8201 and T-DM1.

    Clear MoA

  • Project Introduction

    1. Asset type: Anti-Her2 II / Anti-Her2 IV Bi-specific antibody ADC

    2. Indication: Solid tumor

    3. Research phase: Preclinical

    4. Cooperation demands: License-out or co-development

    5. Research progress:

    (1) Completed proof-of-concept, mechanism research and animal experiments of this project.
    (2) In general, this project is superior to DS8201a and T-DM1 in vitro, and is far more effective than DS8201a or T-DM1 in tumor suppression in vivo.
    (3) The safety of this project has also been verified to some extent, will carry out further toxicological studies in non-human primates, and expect to obtain better results than DS8201a or T-DM1 in toxicological experiments. 2025.

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