Anti-HER3 x MET BsADC BCG022

The in vivo efficacy of BCG022-vcMMAE and BCG022-BLD1102 was evaluated in CDX of gastric cancer, and in PDX models of pancreatic and colorectal cancers. Both conjugates demonstrated strong anti-tumor activity, with efficacy greater than or comparable to that of the benchmark ADCs. Taken together, these preclinical results suggest that the BCG022 bsADC could be a promising novel treatment for HER3 and MET co-expressing tumors.

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  • Highlights of anti-HER3 x MET bsADC
  • About HER3 and MET

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    Highlights of anti-HER3 x MET bsADC
    • The upregulation of HER3 and MET in cancers act as two possible bypass resistance mechanisms, conferring resistance to multiple therapeutic agents, such as EGFR TKIs. They are also expressed in multiple tumor types, including colorectal, gastric, hepatocellular carcinoma, and NSCLC.
    • BCG022 bsAb bound a series of HER3 and MET co-expressing cancer cell lines, including NSCLC, gastric, liver, and colorectal cancer. BCG022 also demonstrated strong endocytosis activity in HER3 and MET co-expressing tumor cells.
    • BCG022 bsAbs conjugated to vcMMAE showed strong anti-tumor efficacy in CDX and PDX models expressing varying levels of HER3 and MET.
    • BCG022 bsAbs conjugated to BLD1102 showed strong anti-tumor efficacy in PDX models expressing varying levels of HER3 and MET.
    • Additional efficacy studies with BCG022-BLD1102 are planned.
    Both BCG022-vcMMAE and BCG022-BLD1102 demonstrated potent anti-tumor efficacy in a HER3-low PDAC PDX model

    (A,B) Efficacy of BCG022-vcMMAE (DAR 4) and BCG022-BLD1102 (DAR 8) in a HER3-low PDAC PDX model. Both BCG022-BLD1102 and BCG022-vcMMAE showed efficacy in controlling growth of BP0209 tumors, with activity superior to patritumab ADCs and comparable to that of telisotuzumab ADCs. H-score values, (histochemical scores) are labelled for BP0209.

    BCG022-BLD1102 showed superior efficacy compared to benchmark ADCs in a colorectal cancer PDX model with moderate HER3 expression

    BCG022-BLD1102 showed greater anti-tumor activity compared to benchmark ADCs in a colorectal PDX model with moderate HER3 expression. Benchmark ADCs, including the patritumab deruxtecan anolog at a higher dose or telisotuzumab vedotin analog at an equivalent dose, showed weak or no activity. H-score values, (histochemical scores) are labelled for BP0170.

    About HER3 and MET

    HER3 and MET expression act as bypass resistance mechanisms, conferring resistance to multiple therapeutic agents, such as EGFR TKI treatment. HER3 and MET are also co-expressed at high prevalence in multiple tumor types, including gastric, colorectal, breast, and non-small-cell lung cancer (NSCLC). In addition, HER3 and MET are frequently overexpressed in liver metastases from patients with colorectal cancer, indicating that targeting both targets may provide clinical benefit.

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