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  Lepu Biopharma and Miracogen have submitted the IND application for MRG006A, an anti-GPC3 ( Glypican-3 ) ADC in China, and the IND application is also expected to be submitted to the US FDA this year. MRG006A MRG006A is a GPC3-targeting ADC composed of a novel humanized IgG1 antibody conjugated to a potent topoisomerase 1 inhibitor via a peptide-based cleavable linker, with a DAR ratio of 8. MRG006A Lepu Biopharma and  Miracogen presented the results of the preclinical study of MRG006A at the 2023 AACR Annual Meeting. Highlights demonstrated its superior binding activity to GPC3-expressing cancer cell lines, rapid internalization, and potent GPC3-dependent cytotoxic activity. In 2022, Miracogen filed a patent (WO2024061305 ) covering the GPC3 ADCs and their use in cancers, including liver cancer.  The ADCs discussed in the examples included several candidates with DAR values ranging from 2 to 4, all of which were tested in the LIV#219 liver cancer PDX model. GPC3 targeting ADCs Curre

 Biosion submitted the IND application for BSI-992, a TROP2 ADC, on April 9th, 2024 in China. The TROP2 targeting antibody, discovered by Biosion, was licensed to OBI Pharma in 2021. OBI ADC Technology OBI Pharma (台灣浩鼎) owns the ex-China right of BSI-992/OBI-992 , with the US FDA clearing  an IND application for a Phase 1/2 Study in Jan 2024. The phase 1 trial in the US is estimated to be completed in 2025Q2. Besides OBI-992, OBI Pharma has also discovered a next-generation anti-TROP2 ADC, OBI-902, using the GlycOBI platform in various drug-antibody ratios (DAR). Furthermore, a BsADC targeting TROP2 and HER2 is currently in the preclinical stage. BSI-992/ OBI-992 OBI-992 is a TROP2-directed antibody-drug-conjugate (ADC) that carries a potent topoisomerase I inhibitor and uses a hydrophilic, enzyme-cleavable linker. Upon binding to TROP2 on the surface of cancer cells, OBI-992 is internalized into the cell and trafficked to lysosomes where the linker is cleaved by cathepsin B, releasing

 Innovent has initiated a phase 1 study (NCT06349408 ) of IBI3001, a bispecific ADC that targets B7-H3 and EGFR, in patients with solid tumors. Additionally, Innovent is conducting a phase 1 trial ( NCT05774873 ) of IBI344, a bispecific antibody that also targets B7-H3 and EGFR. Schematic overview of crosstalk between the EGFR signaling and the B7/CD28 family Recent research has suggested that the overexpression of novel B7/CD28 family proteins, including B7-H3 may be linked to EGFR signaling and could potentially lead to resistance to EGFR-targeted treatments by promoting an immune-depressed environment within the tumor microenvironment. IBI3001 According to the statement by Innovent, IBI3001 is a  site-specifically glycan-conjugated ADC that consists of a topoisomerase I inhibitor  with  multiple anti-tumor mechanisms of action : (1) enhanced EGFR signaling blockade; (2) EGFR- and B7-H3-aided payload internalization and cytotoxicity; and (3) potent bystander killing effects of ADC.