Anti-PTK7×EGFR BsADC BCG017

The concurrent targeting of PTK7 and EGFR using a bsADC could potentially enhance both anti-tumor activity and tumor selectivity in heterogeneous tumors that express both PTK7 and EGFR. Further development involving topoisomerase I inhibitors (TOP1i) conjugates is currently in progress.

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  • Highlights of anti-5T4 x MUC1 bsADC
  • About PTK7 and EGFR

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    Highlights of anti-5T4 x MUC1 bsADC
    • PTK7 and EGFR are two receptor tyrosine kinases that are highly expressed in lung, head and neck, esophageal, colorectal, and other solid tumors.
    • The BCG017 bsAb features an EGFR arm with reduced endocytosis as a monovalent form, which has the potential to reduce EGFR on-target toxicity and widen the clinical window.
    • In CDX models, BCG017-vcMMAE bsADC exhibited superior efficacy compared to the parental PTK7-vcMMAE and demonstrated comparable effectiveness to EGFR-vcMMAE.
    • In two PTK7-low PDX modes, the BCG017-vcMMAE consistently exhibited superior efficacy compared to benchmark and parental single-targeting ADCs, suggesting that targeting PTK7 and EGFR simultaneously can improve anti-tumor activity in heterologous tumors.
    • Further studies on the efficacy of additional PDX modes and conjugated new TOP1i payload are ongoing.
    The PTK7×EGFR bsAb demonstrated increased endocytosis activity compared to the PTK7 Abs

    The PTK7×EGFR demonstrated increased endocytosis activity compared to the anti-PTK7 antibody in double-positive MDA-MB-468 (A) and A431 (B) cell lines. The internalization of monovalent (mv) anti-EGFR was significantly reduced compared to the bivalent form, suggesting that the PTK7×EGFR bsAb can promote the internalization of the PTK7 arm with tumor selectivity for the EGFR arm.

    BCG017-vcMMAE demonstrated potent and enhanced anti-tumor activity in a PTK7-low PDX model

    BCG017-vcMMAE exhibited enhanced anti-tumor efficacy compared to its parental Ab ADCs (A) and benchmark ADCs (B) in a PTK7-low pancreatic PDX model.

    BCG017-vcMMAE exhibited potent and durable antitumor activity in a PTK7-low breast cancer PDX model

    In a low PTK7 expressing breast cancer PDX model, the BCG017-vcMMAE displays enhanced efficacy compared to its parent antibodies-ADCs consistent with the BP0203 data (A), outperforming the benchmark ADCs (B). MRG003 is a clinical-stage EGFR-targeting ADC with MMAE for payload.

    About PTK7 and EGFR

    EGFR is a widely utilized target in various cancer therapies. However, EGFR-based therapies have been challenged by drug resistance and on-target toxicity. EGFR-targeted ADCs represent a promising new therapeutic strategy to address the drug resistance, due to the potent killing effects of the conjugated payload. Furthermore, we hypothesized that the development of a bispecific ADC (bsADC) targeting EGFR and another tumor-associated antigen could help to improve the tumor selectivity with a “1+1” format, thereby limiting the on-target off-tumor toxicity. PTK7, which is expressed on the tumor-initiating cells, belongs to the same receptor tyrosine kinases family as EGFR and is co-expressed with EGFR in multiple types of solid tumors, including lung, head and neck, esophageal, and colorectal cancers.

    Herein, we developed a fully human anti-human PTK7 х EGFR bsAb using our proprietary common light chain RenLite® mouse platform and knobs-into-holes technology that demonstrated high binding and internalization in vitro. The monovalent EGFR antibody reduced internalization as expected.

    Learn more about the RenLite and ADC platform.