RBD4059, a GalNAc-siRNA drug based on our proprietary liver-targeting delivery technology RiboGalSTARTM, is being developed for treatment of thrombotic diseases. RBD4059 inhibits the expression of FXI in hepatocytes to reduce the activation of endogenous coagulation pathways, thus resulting in anticoagulant/antithrombotic effects. As the world’s first and most advanced siRNA drug in clinical development siRNA drug targeting FXI (First-In-Modality), RBD4059’s siRNA-based approach offers distinct advantages over both small molecules and antibodies for FXI inhibition: unlike small molecule drugs which often require daily dosing, RBD4059 can achieve sustained reduction in FXI protein and activity with extended dosing intervals up to several months, Compared to protein-based drugs like antibodies, RBD4059’s, synthetic design and liver-targeted delivery reduce the risk of immune reactions and anti-drug antibodies (ADA) . RBD4059 has completed a phase 1 clinical trial in Australia, and the results showed good safety profile, long-acting and strong inhibitory effectiveness. A clinical trial application for Phase 2a study has been approved by EMA, and the enrollment of all patients was completed. We are planning the next phase of clinical trials for RBD4059 in targeted patient populations.
Mechanism of Action of RBD4059
RBD5044, a GalNAc-siRNA drug based on our proprietary liver-targeting delivery technology RiboGalSTARTM, is being developed for treatment of triglycerides (TGs)-type hypertriglyceridemia. RBD5044 inhibits the expression of ApoC3 (Apolipoprotein C-III) to reduce the TGs level in blood by increasing the uptake of lipoprotein lipase and hepatocyte receptor-mediated residual particle and elevating the hydrolysis of triglycerides (TGs) on triglyceride-rich lipoproteins (TRLs). In preclinical studies, RBD5044 has demonstrated superior ApoC3 protein suppression, and more sustained triglyceride control RBD5044 is the second siRNA globally to enter clinical development that targets ApoC3. It completed the phase I clinical trial in Australia, and the results showed good safety profile，and potent and long-acting efficacy, supporting long-lasting TG control with quarterly or bi-annual dosing schedules，— a paradigm shift from daily drug regimens that significantly enhances patient adherence.. A clinical trial application for Phase 2 study in Europe has been approved and the study is ongoing.
Mechanism of Action of RBD5044
Being developed as the first GalNAc-siRNA drug based on our proprietary liver-targeting delivery technology RiboGalSTARTM for the treatment of Hepatitis B, RBD1016 covers patient population with hepatitis B virus genotypes A-E and I, which represent the vast majority of hepatitis B patients in Europe, the United States and Asia. RBD1016 represents a promising therapeutic opportunity for CHB due to its differentiated intracellular mechanism of action that potentially exerts multiple antiviral effects, particularly the suppression of HBsAg. In Phase 1b clinical study, RBD1016 has demonstrated well tolerated safety profile . Pharmacodynamic data on hepatitis B patients indicate that RBD1016 exhibits a relatively consistent and up to 6-month long-lasting inhibitory effect on HBsAg, HBV DNA, HBV RNA, and HBcrAg.
RBD1016 is one of the most advanced siRNA drugs in global clinical development for patients with chronic HBV infection, including those with HDV co-infection. It can serve as a cornerstone for combination treatments for HBV and a potential leading therapy for chronic HDV.
A Phase 1a study in Australia and as Phase 1b study in Hong Kong have been completed. RBD1016’s Phase 2 global MRCT for treating CHB is ongoing in Sweden and Hong Kong, and it also received IND approval from the NMPA. A clinical trial application for a phase 2a study in Hepatitis D patients has been approved by EMA, and the study is ongoing.
Mechanism of Action of RBD1016
RBD7022, a GalNAc-siRNA drug based on our proprietary liver-targeting delivery technology RiboGalSTARTM, is being developed for the treatment of hyperlipidemia. RBD7022 inhibits the expression of PCSK9 (proprotein convertase subtilisin/kexin type 9), to lower to reduce LDL-R (low-density lipoprotein receptor) lysosomal degradation and to increase the number of LDL-R on the surface of liver cells, thus reducing LDL-C levels in the blood. Currently, a phase 1 clinical trial for RBD7022 have been completed in China. The rights for development, manufacture and commercialization of RBD7022 in Mainland China, HK, and Macau has been licensed out to Qilu Pharmaceutical.
Mechanism of Action of RBD7022
RBD7007, a GalNAc-siRNA drug based on our proprietary liver-targeting delivery technology RiboGalSTARTM, is being developed for treatment of Complement-related diseases. RBD7007 inhibits the expression of complement components in hepatocytes to reduce the overactivation of the complement system, achieving the effect of treating complement-related diseases，such as renal and autoimmune diseases. RBD7007 has demonstrated robust and long-duration pharmacological effects in cynomolgus monkeys. A clinical trial application for a first-in-human study has been approved by EMA, and the study is ongoing.
RBD2080, a GalNAc-siRNA drug based on ’our proprietary liver-targeting delivery technology RiboGalSTARTM, is being developed for treatment of Complement-related diseases. RBD2080 inhibits the expression of complement components in hepatocytes to reduce the overactivation of the complement system, achieving the effect of treating complement-related diseases, such as renal and autoimmune diseases. A clinical trial application for a first-in-human study of RBD2080 has been approved by Australia, and the study is ongoing.
