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Inhibition of Factor XI Using RBD4059: A Novel GalNAc-siRNA With Potent and Durable Antithrombotic Effects

Junshi Liang1, Sofia Nilsson2, Johannes Wikström3

  • 1Suzhou Ribo Life Science Co Ltd, Kunshan City, Jiangsu, China.

JACC. Basic to Translational Science
|June 25, 2025
PubMed

Coagulation factor XI (FXI) is an attractive target for novel antithrombotic drugs because of its minor role in hemostasis, which may address the current unmet medical need regarding a powerful anticoagulant with low bleeding risk. Here, we present RBD4059, the first FXI-targeting GalNAc-siRNA molecule to reach the clinical stage of development. In this study, RBD4059 demonstrated potent FXI inhibition with long duration in mice and monkeys, antithrombotic effects in mouse thrombosis models, and no prolonged bleeding in a mouse tail bleeding model. These findings make RBD4059 a promising candidate for the development of a safe and efficient antithrombotic drug.

Keywords:
anticoagulationfactor XIintrinsic pathwaysiRNAthrombosis

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