Anti-FOLR1 x MUC1 BsADC BCG023

BCG023 exhibited superior tumor growth inhibition compared to benchmark ADCs conjugated with the same payload and DAR in a low FOLR1-expressing NSCLC PDX model. These data suggest that targeting FOLR1 and MUC1 with a bispecific ADC is a promising therapeutic strategy for the treatment of ovarian and other tumors. We will continue testing in additional PDX models and use a novel TOP1i payload as a conjugate for further preclinical development.

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  • Highlights of anti-FOLR1 x MUC1 bsADC
  • About FOLR1 and MUC1

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    Highlights of anti-FOLR1 x MUC1 bsADC
    • Through immunohistochemistry (IHC) analysis, we observed a high co-expression of FOLR1 and MUC1 in ovarian cancer PDX samples. Similarly, RNAseq analysis revealed co-expression in ovarian cancer, breast cancer and NSCLC.
    • The BCG023 bsAb bound to multiple cancer cells, including ovarian, lung, and breast cancer.
    • The BCG023 bsAb showed enhanced internalization in two cell lines expressing both FOLR1 and MUC1, with different internalization activity depending on FOLR1 and MUC1 expression. Note: this is accurate, but be prepared to explain the data from the other two cell lines if asked.
    • The BCG023-MMAE showed potent anti-tumor activity in a FOLR1-low PDX model, with improved efficacy over benchmark ADCs.
    • Additional in vivo efficacy studies are ongoing.
    BCG023 bsAb demonstrated enhanced internalization in certain cell lines

    (A-D) Internalization of BCG023 bsAb in four mammalian cell lines. Internalization was measured with a pH sensitive dye by FACS. BCG023 bsAb showed superior to benchmarks internalization activity, and enhanced internalization compared to parental Abs in MDA-MB-468 (C) and T47D (D) tumor cell lines. The anti-FOLR1 Ab showed stronger or comparable activity to benchmarks in all cell lines.

    BCG023 bsADC showed potent anti-tumor activity in a TNBC CDX model

    (A) Efficacy study of BCG023 bsADC in a TNBC MDA-MB-468 xenograft model. All ADCs were conjugated to vcMMAE with the same DAR (~4). The anti-FOLR1-MMAE demonstrated stronger anti-tumor efficacy compared to the two FOLR1 benchmark ADCs, and the BCG023-vcMMAE showed comparable efficacy to that of the FOLR1 benchmark ADCs. The body weight of the mice did not decrease over the period of study. (B).

    BCG023 bsADC demonstrated superior anti-tumor efficacy in a NSCLC PDX model with low FOLR1 expression compared to benchmark ADCs

    BCG023 bsADC exhibited potent anti-tumor efficacy in a FOLR1-low NSCLC PDX model.
    (A) Expression of FOLR1 and MUC1 in the PDX.
    (B, C) Efficacy studies of BCG023-vcMMAE. All ADCs carried the same payload (vcMMAE) with the same DAR of ~4, except for Gatipotuzumab analog-Dxd (DAR ~8). The BCG023-MMAE was more effective in the PDX model than the benchmark ADCs, and showed increased efficacy compared to the parental MUC-1 ADC alone or MUC-1 and FOLR1 ADCs in combination.

    About FOLR1 and MUC1

    Folate receptor alpha (FOLR1) is specifically overexpressed in malignant tumors of epithelial origin, including ovarian, lung and breast cancers. While antibody-drug conjugate (ADC) therapies targeting FOLR1 have shown promise in clinical trials, there is still a large proportion of patients, particularly those with low FOLR1 expression, who do not respond, indicating new therapeutic strategies are needed. MUC1 is another tumor-associated antigen that is likewise overexpressed in epithelial ovarian cancer, breast cancer, and NSCLC, among other cancers; analysis of ovarian PDX tumors by immunohistochemistry (IHC) suggests that FOLR1 and MUC1 are both highly expressed in this cancer type.

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