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 and plasma cells and potently recruits and activates innate 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 maintains activity in the context of CD16a downregulation. This allows the bispecific to productively engage CD16a-low or -negative innate cell subpopulations
Unlike conventional monoclonal antibodies that require high levels of target antigen for efficacy, CTX-8573 potently induces NK cell activation and killing of tumor and plasma 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 or plasma cells, lowering the risk of off-target toxicities validating its therapeutic potential in oncology and autoimmune indications. 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.