ATOR-4066, a Neo-X-Prime bispecific antibody targeting CD40 and CEACAM5, induces strong myeloid and T cell dependent tumor immunity

ATOR-4066 is a bispecific antibody that targets CD40 and CEACAM5 developed for immunotherapy of cancer using the Neo-X-Prime platform. ATOR-4066 shows potent CEACAM5-dependent activation in vitro with ability to activate intratumoral immune cells from patient derived material. In vivo, ATOR-4066 induced superior anti-tumor activity compared to CD40 mAb in MC38-CEA tumors and cured mice with well-established tumors with a heterogeneous CEACAM5 expression. Using RNA sequencing, we show that ATOR-4066 promotes immune cell trafficking to tumors and activates both myeloid cells and T cells within the tumor microenvironment, with limited immune activation in the periphery. RNAseq of lymph nodes, blood, whole tumors and CD45+Ly6G- cells from tumors from hCD40tg mice inoculated with MC38-CEACAM5 tumors and treated with either vehicle, CD40 mAb or ATOR-4066.