Anti-PTK7 x TROP2 BsADC BCG033

BCG033 conjugates demonstrate promising preclinical efficacy in vivo, which ultimately could provide a new treatment option for TNBC and other solid tumors expressing PTK7 and TROP2.

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  • Highlights of anti-PTK7 x TROP2 bsADC
  • About PTK7 and TROP2

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    Highlights of anti-PTK7 x TROP2 bsADC
    • Co-expression of PTK7 and TROP2 in multiple solid tumors suggests that simultaneous targeting of PTK7 and TROP2 with bsADC has the potential to enhance efficacy and improve safety.
    • BCG033 is an PTK7 and TROP2 targeting bsADC derived from the proprietary, RenLite® common light chain, fully human antibody technology.
    • BCG033 is designed with selected TROP2 arm to have reduced binding and internalization capability at its monovalent form, with the purpose of reducing the known skin toxicity of TROP2 targeting.
    • BCG033 bsADC (both vcMMAE and BLD1102 conjugates) demonstrated potent anti-tumor activity in multiple CDX and PDX models, with improved efficacy over parental mAb ADCs in certain models, showing a synergistic effect.
    • BCG033-BLD1102 consistently exhibited strong and long-lasting enhanced antitumor efficacy than benchmark ADCs in various PTK7 and TROP2 expressing models, indicating that BCG033 bsADC has strong therapeutic potential in PTK7 and TROP2 expressing cancers.
    BCG033-vcMMAE showed a synergistic effect to increase efficacy in both TNBC CDX and PDX xenografts

    Note: All MMAE-ADCs with a DAR of about 4
    We first tested the anti-PTK7×TROP2 bsAb conjugate with vcMMAE (refer to BCG033-vcMMAE) for in vivo efficacy. The bsADC showed improved efficacy compared to the parental monoclonal Ab-ADCs in both TNBC CDX and PDX models, suggesting that bsADC has a synergistic effect and could overcome tumor heterogeneity.

    BCG033 consistently demonstrated superior efficacy over benchmark ADCs in multiple tumor models

    The BCG033 bsAb conjugated to BLD1102, a novel proprietary linker/payload composed of a DNA topoisomerase I inhibitor payload and a highly hydrophilic protease-cleavable linker, with a DAR of 8, are named BCG033-BLD1102.
    BCG033-BLD1102 showed robust efficacy in two PDX models, outperforming benchmark ADCs.

    About PTK7 and TROP2

    Metastatic triple-negative breast cancer (TNBC) patients have poor overall survival, highlighting the need for novel treatments. Although the TROP2-targeting ADC sacituzumab govitecan recently received accelerated approval from the FDA for the treatment of patients with metastatic TNBC, the on-target toxicity of this single-target agent has limited clinical efficacy. We sought to improve the specificity and efficacy of future TNBC-targeted therapies by generating a bispecific antibody-drug conjugate (bsADC) targeting TROP2 and PTK7, another tumor-associated antigen (TAA) that is highly expressed in TNBC and correlates with poor prognosis and metastatic disease.

    Learn more about the RenLite and ADC platform.