RBD4059 is a GalNAc-conjugated small-interfering RNA (siRNA) drug independently developed by Suzhou Ribo Life Science. Ltd (Ribo) based on the RIBO-GalSTARTM liver targeting technology platform. RBD4059 achieves antithrombotic effects by silencing the FXI protein expression by RNA interference and thereby blocking the activation of the endogenous coagulation pathway.
The results of the current preclinical study show that RBD4059 exhibits potent and long-lasting FXI inhibition in mice and cynomolgus monkeys measured by reduced FXI activity and prolonged aPTT (activated partial thromboplastin time). In FeCl3-induced mouse models of arterial and venous thrombosis, RBD4059 effectively inhibit the decrease in blood flow velocity caused by thrombosis in blood vessels, showing significant antithrombotic efficacy. Unlike the standard antithrombotic treatment Enoxaparin, RBD4059 did not cause prolonged bleeding time compared to PBS in the mouse tail bleeding model, indicating a low risk of bleeding with RBD4059.
Ribo is a pioneer in the research and development of siRNA drugs, having successfully obtained five clinical approvals based on the RIBO-GalSTARTM liver-targeted delivery platform. The company has made significant strides in the field of coagulation, with RBD4059 being the first GalNAc-siRNA molecule targeting FXI to enter clinical development. RBD4059 is long-acting and highly effective at inhibiting FXI activity, holding promise as a more potent antithrombotic agent with a lower risk of bleeding compared to existing therapies. Currently, RBD4059 is in a Phase II clinical trial at Ribo’s clinical R&D center, Ribocure Pharmaceuticals, in Sweden.
“We are excited to present our comprehensive preclinical data package, which supports our first- and best-in-class clinical asset currently in the midst of Phase 2 clinical trials within the target patient population. With Phase 1 clinical data now available, we are thrilled to see a strong translation from preclinical to clinical settings, validating the safe and robust performance of our GalNAc platform. Notably, the clinical efficacy of RBD4059 has proven to be even greater than the data from animal models in terms of both potency and duration.” says Li-Ming Gan, Co-CEO and President of R&D of Ribo.
The results are published in JACC: Basic to Translational Science on February 19th 2025
Title: “Inhibition of Factor XI Using RBD4059: A Novel GalNAc-siRNA With Potent and Durable Antithrombotic Effects”
Authors: Junshi Liang, Sofia Nilsson, Johannes Wikström, Huiqing Cao, Shuquan Zheng, Qian Xu, Xu Yan, Sebastian Ueckert, Qi Sun, Chun Guo, Hongyan Zhang, Zicai Liang, Shan Gao, Li-Ming Gan
Inhibition of Factor XI Using RBD4059: A Novel GalNAc-siRNA With Potent and Durable Antithrombotic Effects | JACC: Basic to Translational Science
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