Discovery of mutation-independent EGFR degrading bispecific antibodies that suppress tumor growth in preclinical tumor models
Poster presentation, AACR 2024
Key messages
EpiTACs are bispecific antibodies with a target binding arm and degrader binding arm that together localize degradation of extracellular and membrane targets to disease tissue, sparing normal tissue and increasing efficacy.
Novel EpiTACs were rapidly selected and tested using the EpiAtlas of 270+ tumor- and tissue-specific degraders, including transmembrane E3 ubiquitin ligases, chemokine/cytokine receptors and tissue-enriched internalizing receptors.
EpiTAC protein degradation represents a promising new drug modality with multiple advantages over conventional treatment options, including improved efficacy and tissue- and disease-selectivity achieved through an actively expanding EpiAtlas of degraders.
Our preclinical data demonstrate that EpiTAC-driven degradation of EGFR:
is independent of EGFR mutational status and can overcome resistance mutations that arise with standard-of-care;
abrogates downstream signaling pathways in vitro and in vivo, which is not seen with blocking mAbs;
drives robust in vitro tumoricidal activity in colorectal cancer and non-small cell lung cancer organoid models, independent of KRAS status;
drives robust in vivo anti-tumor activity and survival benefit beyond standard-of-care in multiple preclinical tumor models.
