Targeting Multiple Myeloma: BI 836909's Specific and Potent T Cell Engager Therapy

BI 836909 is a BiTE that directs the body's T cells to target cells expressing BCMA. BCMA is a plasma cell-specific antigen predominantly found on the surface of certain cancer cells, making it a suitable target for therapy. The drug's action is due to its binding to the CD3 epsilon subunit on T cells and BCMA on cancer cells, leading to the destruction of BCMA-expressing cells.

In laboratory tests, BI 836909 showed a dose-dependent effect on multiple myeloma cell lines, with no impact on BCMA-negative cells, indicating its specificity. It also activated T cells and induced cytokine release in the presence of BCMA-positive cells.

Animal studies using human T cell-reconstituted mice with myeloma xenografts demonstrated BI 836909's anti-tumor activity. In subcutaneous models, significant tumor reduction was observed with daily doses of 50 μg/kg or higher, with comparable efficacy between intravenous and subcutaneous administration. In orthotopic models, survival was significantly prolonged with doses of 5 μg/kg/day or higher.

BI 836909 also exhibits cross-reactive binding to human and macaque BCMA and CD3 epsilon, allowing for pharmacodynamic, pharmacokinetic, and safety assessments in non-human primates. Toxicity studies in cynomolgus monkeys showed a dose-dependent reduction in plasma cells in bone marrow, consistent with BCMA expression and demonstrating the drug's pharmacological activity.

The pre-clinical findings suggest BI 836909 is a potent, effective, and BCMA-selective T cell redirecting agent, warranting further clinical evaluation in multiple myeloma patients. The disclosures section mentions affiliations with Boehringer Ingelheim and Amgen Research entities.