RiboBio’s Novel GalNAc-siRNA RBD4059 Demonstrates Potent and Durable Antithrombotic Effects with Low Bleeding Risk in Preclinical Studies

On February 19, a preclinical research article on RBD4059, a clinical pipeline of Suzhou Ribo Life Science Co., Ltd. ("Ribo Life Science"), was published in the journal *JACC: Basic to Translational Science*, a subsidiary of the *Journal of the American College of Cardiology*. The article, titled "Inhibition of Factor XI Using RBD4059: A Novel GalNAc-siRNA With Potent and Durable Antithrombotic Effects," showcases Ribo Life Science's capability and confidence in developing FIC and BIC small nucleic acid drugs, while also offering hope for revolutionary treatments in the antithrombotic field.

RBD4059 is a product developed by Ribo Life Science based on RIBO-GalSTAR.^TMRBD4059, a GalNAc-conjugated siRNA drug independently developed by the liver-targeting technology platform with global rights, achieves its anticoagulant/antithrombotic effect by inhibiting Factor XI and blocking the activation of the intrinsic coagulation pathway. The study results show that RBD4059 exhibits potent and long-lasting Factor XI inhibition in mice and cynomolgus monkeys by suppressing Factor XI activity and prolonging APTT (Activated Partial Thromboplastin Time). In both arterial and venous thrombosis models, RBD4059 effectively prevents thrombosis-induced reduction in blood flow, demonstrating significant antithrombotic efficacy. In bleeding models, RBD4059 does not prolong bleeding time, indicating a low risk of bleeding.

    Dr. Gan Liming, Co-CEO of Ribo Life Science and President of Global R&D, stated:"We are delighted to present to the public our comprehensive and detailed preclinical data, which strongly support RBD4059 as the first and best-in-class product. We are currently conducting Phase II clinical trials in the target patient population. Excitingly, although small nucleic acid drugs have shown good translation from preclinical to clinical research, in terms of potency and durability, the Phase I clinical data of RBD4059 is still significantly better than the animal model data, which once again confirms the excellent safety and potency characteristics of Ribo Life Science's RIBO-GalSTARTM platform."

Ribo Life Science is a global leader and pioneer in the research and development of small nucleic acid drugs, based on RIBO-GalSTAR.^TMThe liver-targeted delivery technology platform has successfully advanced six products into the clinical development stage, with extensive deployment in the cardiovascular, metabolic, and renal disease fields. RBD4059, as the first GalNAc-siRNA molecule targeting Factor XI to enter clinical development, demonstrates superior efficacy, longer duration, and a lower risk of bleeding compared to existing antithrombotic therapies. Existing Phase I clinical results show that RBD4059 exhibits dose-dependent, predictable pharmacokinetic properties, along with significant (>90%) and sustained reductions in FXI activity and protein levels. Additionally, it met primary endpoints for safety and tolerability, with no adverse safety signals detected within the studied dose range, indicating favorable safety. Currently, RBD4059 is undergoing Phase II clinical trials in Europe.