BI 905677

BI 905677 is a novel tri-molecular antagonistic antibody designed to inhibit the Wnt/β-catenin signaling pathway by targeting the low-density lipoprotein receptor-related protein co-receptors LRP5 and LRP6. The drug consists of two modules that bind distinct domains on both LRP5 and LRP6, thereby blocking Wnt ligand-dependent pathway activation, and a third module that binds human serum albumin to improve pharmacokinetics by reducing glomerular filtration. The antibody modules are derived from camelidae heavy-chain antibodies (nanobodies). Preclinical studies demonstrated potent inhibition of Wnt/β-catenin signaling in models with aberrant ligand-dependent Wnt activation due to RNF43 mutation or RSPO fusion. In clinical trials for advanced solid tumors, BI 905677 showed target engagement but was associated with dose-limiting toxicities at higher doses. It was developed primarily for oncology indications such as colorectal cancer, triple-negative breast cancer, and non-small cell lung cancer.

Other names

LRP5/6 antagonist BI 905677