84-EBET

**84-EBET** is an investigational antibody-drug conjugate (ADC) designed for targeted cancer therapy. It consists of the CEACAM6-targeted monoclonal antibody #84.7 conjugated via a cathepsin B-cleavable linker (GGFG) to EBET, a small-molecule degrader of bromodomain and extra-terminal (BET) proteins. Mechanistically, 84-EBET delivers the BET degrader specifically to CEACAM6-expressing tumor cells, leading to potent proteasomal degradation of BET proteins such as BRD4 in both cancer and stromal cells through a bystander effect. This results in direct antitumor cytotoxicity and modulation of the tumor microenvironment by inhibiting inflammatory and immunosuppressive phenotypes in cancer-associated fibroblasts (CAFs). In preclinical models, 84-EBET has demonstrated broad-spectrum efficacy with significant tumor regression in pancreatic, colorectal, lung, and breast cancer xenografts, outperforming other clinically approved ADC payloads. Additionally, 84-EBET enhances the efficacy of PD-1 antibody immunotherapy and standard chemotherapies without increasing toxicity or body weight loss[1][2][3][4].