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

In April, the U.SFDA accelerated approval of the application of the antibody-conjugated drug Trodelvy (sacituzumab govitecan-hziyy), developed by Immunomedics, to treat metastatic triple-negative breast cancer (mTNBC)It is also the first FDA-approved antibody coupling drug to target TROP2A number of biopharmaceutical companies are currently developing antibody coupling drugs that target TROP2Why is the TROP2 protein 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 TROP2TROP2: Potential emerging targetforthed for multiple cancers, TROP2 is a cell surface glycoprotein, also known as tumor-related calcium ion signal transconductor 2 (TACSTD2), which is encoded by the TACSTD2 genePrevious studies have shown that it has different levels of expression in human health tissue, with the highest levels of expression being the epithelial tissue of the breast, kidneys, and pancreasThe concern of drug developers is that TROP2 has significantly increased expression levels in a variety of tumors, including breast, lung, stomach, colorectal, pancreatic, prostate, cervical, head and neck, and ovarian cancer, regardless of the level of expression in healthy tissueThe high expression of TROP2 plays a key role in tumor growth and is also associated with more aggressive diseases and poor prognosisBecause 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 developmentTargeting TROP2 ADCs has the potential to treat a wide range of cancer typesTo improve the efficacy/safety characteristics of the ADC, ADC plays a directional effect by connecting monoclonal antibodies that target TROP2 with cytotoxic drug loads (payloads) and qualitatively delivering the payloads of killer cells to tumors that are highly expressed as TROP2The design of the ADC has been iterative since the 1970s, and great progress has been made in the selection of cytotoxic drugs and in the design of linker stol connecting antibodies to payloadsThe first three developments of the DS-1062 and the Development of The Trodelvy of Immunomedics reflect technological advances in ADC designIn the case of DS-1062, this ADC uses the first three-third-of-the-kind DXd ADC technology to link monoclonal antibodies targeting TROP2 with innovative DNA topological iwasanase I inhibitors (DXd), which has a unique mechanism of action that increases activity by 10 times compared to the common chemotherapy drug iritcannoteAnd it has the ability to penetrate the cell membrane, allowing them to kill nearby cancer cells after killing them into the ADC' cancer cells, creating a "bystander effect."Moreover, the optimization of dS-1602's coupling technology allows the drug antibody ratio (DAR) to be mostly 4, giving better control over its safetyIn terms of connecting sons, DS-1602 connecting sons can be specifically cut by a highly expressed lysosome protease in the tumor DS-1062 introduction (Photo: 1st All-In-One) The Trodelvy developed by Immunomedics uses Ilitikon's metaboliteSN-38 as a cytotoxic drug It is three times more toxic than Yilithon The connector developed by Immunomedics enables Trodelvy's drug antibody ratio (DAR) to reach 7 and protects SN-38 activity In animal models, this ADC was able to increase SN-38 levels delivered to near tumors by 120 times compared to receiving Iletikon treatment Immunomedics, which does not select ultra-toxic drugs as a load, believes it can provide better treatment indicators by increasing DAR and allowing repeated administration Trodelvy's structural schematic (Photo: Immunomedics) The treatment of a variety of cancer types has shown promising efficacy Because TROP2 is highly expressed in many types of cancer, one of the most attractive reasons for targeting it is that a DC can be used to treat many different cancers According to preliminary clinical trial data released by The First Three Republicans, DS-1602 and Trodelvy also showed encouraging results 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 phase 1 clinical trial results (picture source: 13 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) Several 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 them, 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 three-line treatment from 2020 to 2021, a registration trial for three-line treatment of HR/HER2-metastatic breast cancer (mBC), a registration trial for second/third-line treatment of helioblastoma on the metastatic urethra, and a basket trial in Asia In addition, Genting Plans plans to submit a listing application for the product 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 Related: 1: Daiichi Sankyo and AstraZeneca Enter New Global Development and Commercialization Collaboration for Daiichi Sankyo's ADC DS-1062 Retrieved Jul 27, 2020, from s2 s 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 [4] ASCO 2020 Highlights Retrieved Jul 27, 2020, from ADC Linker Retrieved Jul 27, 2020, from .6 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?