NB003

NB003 is a fully humanized CEACAM1 blocking mAb. NB003 exhibits its anti-tumor function via enhancement of natural killer cell and T cell function, reduction in tumor metastasis and polypoidization.

CEACAM1, also known as the carcinoembryonic antigen cell adhesion molecule 1, serves as an inhibitory receptor that downregulates the functions of T cells and NK cells. Like CTLA4 and PD-1, CEACAM1 possesses an immunoreceptor tyrosine-based inhibitory motif (ITIM). Its interactions with ligands, both homophilic and heterophilic, result in the suppression of NK and T cell activity through the ITIM pathway, facilitating tumor growth and migration. Furthermore, CEACAM1 collaborates with TIM-3, contributing to TIM-3's inhibitory effects by promoting its maturation and localization to the T cell surface. Multiple studies have revealed a correlation between the maximal exhaustion state of T cells and the co-expression of CEACAM1 and TIM-3, highlighting the critical role of CEACAM1 in tumor progression and resistance.

NB003 is a fully humanized monoclonal antibody that blocks CEACAM1, discovered through NeologicsBio's Tier-A platform. It selectively binds to human CEACAM1 with high affinity in the nanomolar (nM) range, and effectively dampens its inhibitory effects on NK and CD8 T cells as demonstrated by increased in IFNγ production. Additionally, NB003 directly influences the growth and migration of tumor cells expressing either CEACAM1 or CEACAM5, as evidenced in humanized murine models of melanoma and pancreatic cancer. The comprehensive pre-clinical data supports the notion that NB003 significantly enhances NK cell cytotoxicity, modulates T cell immune activation, and restricts tumor growth and migration. As a result, NB003 holds promise as a targeted therapy for cancer, either as a stand-alone treatment or in combination with existing therapies.

View Poster Presentation AACR Annual Meeting 2023

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