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

Area of Science:

• Pharmacology
• Thrombosis Research
• Drug Development

Background:

• Coagulation factor XI (FXI) is a potential target for antithrombotic drugs.
• Current anticoagulants carry a risk of bleeding.
• There is a need for safer and effective antithrombotic therapies.

Purpose of the Study:

• To evaluate RBD4059, a novel GalNAc-siRNA targeting FXI.
• To assess the efficacy and safety of RBD4059 as an antithrombotic agent.

Main Methods:

• RBD4059 administration in mouse and non-human primate models.
• Assessment of FXI inhibition and duration.
• Evaluation of antithrombotic activity in thrombosis models.
• Analysis of bleeding risk in a mouse tail bleeding model.

Main Results:

• RBD4059 demonstrated potent and long-lasting FXI inhibition in mice and monkeys.
• The drug exhibited significant antithrombotic effects in preclinical models.
• No prolonged bleeding was observed in the mouse tail bleeding model.

Conclusions:

• RBD4059 is the first FXI-targeting GalNAc-siRNA to enter clinical development.
• RBD4059 shows promise as a safe and effective antithrombotic drug with a low bleeding risk.