CTX-8573 is a first-in-class, common light chain-based NKp30 x BCMA bispecific antibody that targets B-cell maturation antigen (BCMA) positive tumor cells and potently recruits and activates NK and γδ T cells through engagement of the activating receptor NKp30, as well as the activating receptor CD16a through an intact Fc. Compared to monoclonal antibodies that only engage CD16a, the NKp30 bispecific platform increases ADCC potency more than 100-fold, and also maintains activity in the context of CD16a downregulation. This allows the bispecific to productively engage CD16a-low or -negative NK subpopulations that are enriched in certain tumor settings.
Unlike conventional monoclonal antibodies that require high levels of target antigen for efficacy, CTX-8573 potently induces NK cell activation and killing of tumor cells that express high, medium and low levels of BCMA. Importantly, CTX-8573 does not activate NK cells in the absence of BCMA-positive tumor cells, lowering the risk of off-target toxicities. Due to its common light chain-based molecular structure, CTX-8573 is highly manufacturable with expression, purity, stability, and pharmacokinetics essentially identical to a monoclonal antibody.
Preclinical data on the NKp30 x BCMA platform was presented at the 2018 Society for Immunotherapy of Cancer (SITC) annual meeting and the 2019 American Association for Cancer Research annual meeting.