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    Home > Medical News > Medical World News > Why TROP2 antibody coupling drugs are a hot research and development area.

    Why TROP2 antibody coupling drugs are a hot research and development area.

    • Last Update: 2020-08-02
    • Source: Internet
    • Author: User
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    Today, AstraZeneca and Daiichi Sankyo jointly announced a joint development agreement to jointly develop antibody conjugate dS-1062 (ADC) to target the surface glycoprotein antigen 2 (ADC) of the human nourishing layer cells.
    , AstraZeneca has agreed a $6.9 billion partnership with First Three to target her2 antibody conjugated drug Enhertu (DS-8201).
    Enhertu was approved to treat HER2-positive breast cancer patients in December, but this year's ASCO annual meeting also showed promising results in a variety of other cancer types that express HER2, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and stomach cancer.
    today's partnership, which totals $6 billion, reflects AstraZeneca's recognition of the potential of DS-1062.
    April, the U.S. FDA accelerated approval of The Acetotics, an antibody-conjugated drug developed by Immunomedics, to treat metastatic triple-negative breast cancer (mTNBC) patients.
    this is also the first FDA-approved antibody coupling drug to target TROP2.
    a number of biopharmaceutical companies are currently developing antibody coupling drugs that target TROP2. Why
    TROP2 protein is a hot target for ADC development? What types of cancer can ADCs target ING2 treat? Today, the potion-Conde content team will introduce TROP2 as an emerging target and the ADC research and development pipeline targeting TROP2.
    TROP2: Potential emerging targetforthed for multiple cancers, TROP2 is a cell surface glycoprotein, also known as tumor-related calcium ion signal transformer 2 (TACSTD2), encoded by the TACSTD2 gene.
    previous studies have shown that it has different levels of expression in human health tissue, with the highest levels of expression being the upper skin tissue of the breast, kidneys, and pancreas.
    attracting the attention of drug developers, TROP2's expression levels in a variety of tumors, including breast, lung, stomach, colorectal, pancreatic, prostate, cervical, head and neck, and ovarian cancer, are significantly higher, regardless of the level of expression in healthy tissue.
    high expression of TROP2 plays a key role in tumor growth and is also associated with more aggressive diseases and poor prognosis.
    because TROP2 is widely expressed in a variety of solid tumors and is located on the cell surface, it is one of the hot targets of ADC research and development.
    targetING TROP2 ADCs has the potential to treat a wide range of cancer types.
    the same way, improve the efficacy/safety characteristics of ADC ADC by targeting TROP2 monoclonal antibodies, with cytotoxic drug load (payload) connected to the killer cell load qualitative delivery to the highly expressive 2 tumor near, thus playing a targeted effect of the drug delivery.
    ADC design has been iterative since the 1970s, and great progress has been made in the selection of cytotoxic drugs and in the design of linker stoics connecting antibodies to payloads. Both the DS-1062 and the Trodelvy development by Immunomedics, developed by
    , reflect technological advances in ADC design.
    , using the first-three-to-three DXd ADC technology, the ADC links monoclonal antibodies targeting TROP2 with innovative DNA-top isomease I inhibitors (DXd), which has a unique mechanism of action that increases activity by 10 times compared to the common chemotherapy drug iricannote.
    and it has a strong ability to penetrate the cell membrane, allowing them to kill nearby cancer cells after killing them, creating a "bystander effect."
    , the optimization of dS-1602's coupling technology allows the drug antibody ratio (DAR) to be mostly 4, giving better control over its safety.
    in the connection, DS-1602 connecters can be specifically cut by the highly expressed lysosome protease in the tumor.
    ,DS-1062 introduction (Photo: 1st- and third-party website) By The Trodelvy, inc., uses Ilitikon's metaboliteSN-38 as a cytotoxic drug.
    its toxicity is three times more toxic than that of Ilitikon.
    the connection developed by Immunomedics, which enables Trodelvy's drug antibody ratio (DAR) to reach 7 and acts as a protective SN-38 activity.
    in animal models, this ADC was able to increase SN-38 levels delivered to near tumors by 120 times compared to treatment with Elithion.
    Immunomedics did not select ultra-toxic drugs as a load, and the company believes that by increasing DAR and allowing repeated administration, it can provide better treatment indicators.
    's diagram of the structure of Trodelvy (Photo: Immunomedics) The treatment of a variety of cancer types has shown promising efficacy due to the high expression of TROP2 in many types of cancer, one of the most attractive reasons for targeting it is that a ADC can be used to treat many different cancers.
    , dS-1602 and Trodelvy also showed encouraging results, according to preliminary clinical trial data released by 13th-third-year-old Immunomedics.
    DS-1602 achieved an objective remission rate (ORR) of 27% when treating most patients with non-small cell lung cancer (NSCLC) who received 3 pre-treatments.
    dS-1062 treatment of NSCLC patients in Phase 1 clinical trial results (picture d'etre source: The first three co-website) and Trodelvy in the treatment of metastatic triple negative breast cancer patients showed good results, in the treatment of metastatic urinary tract skin cancer, as well as HR positive, HER2 negative breast cancer patients also reached about 30% R.
    Trodelvy has the potential to change the treatment model for breast cancer and pee-road skin cancer (Photo: Immunomedics) A number of Chinese biopharmaceutical companies have joined TROP2 antibody conjugated drug development in China, and a number of biopharmaceutical and technology companies have begun to develop antibody conjugate drugs that target 2. among
    , Everest Medicines, founded by Kangqiao Capital, last year entered into an exclusive licensing agreement with Immunomedics, which acquired Trodelvy's development and promotion interests in Greater China, South Korea and some south Asian countries and regions.
    currently, the company plans to conduct a bridging registration trial for mTNBC's third-line treatment from 2020 to 2021, a registered trial of a third-line treatment for HR/HER2-metastatic breast cancer (mBC), a registered trial for second/third-line treatment of helioblastoma on the metastatic urethra, and a basket of Asian trials.
    , Genting Plans plans to submit an application for listing in China by the end of 2021 or the first half of 2022.
    , in addition, the TROP2 antibody coupling drugs developed by companies such as Baxter, Collum Pharmaceuticals and Hangzhou Polybiosa have also entered or are about to enter the clinical development phase.
    References: 1. Daiichi Sankyo and Astra Zeneca Enter New Global Development and Commercialization Collaboration for Daiichi Sankyo's ADC DS-1062. Retrieved July 27, 2020, from Zaman et al., (2020). Targeting Trop-2 in solid tumors: future. Onco Targets Ther., doi: 10.2147/OTT. S162447. DS-1062 Strategic Collaboration. Retrieved July 27, 2020, from ASCO 2020 Highlights. Retrieved July 27, 2020, from ADC Linker. Retrieved July 27, 2020, from Corporate Presentation. Retrieved DJul 27, 2020, from the original title: Before FDA Accelerated Approval, now a $6 billion co-development by AstraZeneca, why is THE TROP2 antibody conjugate dating drug a hot research and development area? Follow the Micro-Wei Public Number of "Drug Mingkang" .
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