BI 905681

BI 905681 is a novel, intravenously administered antagonist of the low-density lipoprotein receptor-related protein 5 (LRP5), developed for its potential antineoplastic and immunomodulating activities. It consists of three modules (nanobodies connected by two peptide linkers): two bind to distinct epitopes on LRP5 (biparatopic) and one binds to human serum albumin for half-life extension. By targeting and binding to LRP5, BI 905681 blocks the binding of Wnt ligands to this coreceptor, thereby inhibiting Wnt/β-catenin signaling—a pathway implicated in cancer cell proliferation and survival. Preclinical studies demonstrated that BI 905681 effectively inhibits ligand-dependent Wnt signaling in models with RNF43 mutations, showing antitumor activity in vitro and in vivo. A phase I clinical trial evaluated its safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy in patients with advanced or metastatic solid tumors who had no standard treatment options remaining; however, the trial was terminated early due to enrollment difficulties[1][2][3][4][7].

Other names

LRP5 antagonist BI 905681LRP-5 antagonist BI 905681LRP 5 antagonist BI 905681