CTX-8573 / NKp30 x BCMA

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.

NKp30 x TAA

The NKp30 bispecific engager platform originally developed for targeting BCMA is a highly modular format that can be extended to other tumor-targeting antibodies against hematological and solid tumor antigens. Using our common light chain discovery platform, Compass scientists have generated NKp30 bispecific engagers targeting diverse indications including NHL and breast cancer, with additional programs for prostate and ovarian cancer in progress. Our lead NKp30 x Her2 bispecific demonstrates enhanced activity compared to trastuzumab (Herceptin) targeting cells with a wide range of Her2 expression.

TGFβtrap x TIGIT

Compass’ TGFβ x TIGIT bispecific is a novel therapy designed to neutralize TGFβ, a highly immunosuppressive cytokine that is overproduced by many tumors, while simultaneously blocking the immune inhibitory receptor TIGIT (T cell immunoreceptor with Ig and ITIM domains) commonly expressed on exhausted T and NK cells. Unlike other TIGIT blockers currently in development, Compass’ TIGIT blocker is a non-depleting, pure antagonistic antibody.