Suzhou Ribo Life Science (Ribo) and Ribocure Pharmaceuticals (Ribocure) presented new data from three projects from its cardiovascular pipeline at the European Society of Cardiology Congress (ESC) in Amsterdam on August 25-28, the world’s largest and most influential conference in cardiology. Building on its proprietary liver-targeting platform RIBO-GalSTAR®, highly specific, potent and durable gene silencing effects knock down disease causing genes in the liver. Data from three successful siRNA therapeutic programs within the field of thrombosis (FXI), dyslipidemia (APOC3) and hypertension (AGT) were presented. The presentations fully reflect Ribo’s and Ribocure’s determination to be a key player in the cardiovascular field using the mature RNA interference technology platform.
World´s first hemostasis sparing antithrombotic drug with high potency and long duration – inhibition of Factor XI (FXI) using a GalNAc-siRNA conjugate (RBD4059)
Accumulating data supports that by only inhibiting the intrinsic coagulation pathway via FXI blockade provides a new efficacious antithrombotic approach with low bleeding risk. Using RNAi approach targeting FXI, Ribo presented the key safety and efficacy data from its preclinical IND-enabling data package, showing the high potency and long duration of its FXI gene silencer. It is anticipated that high patient compliance, and a long durable effect can be achieved, at the same time with no need for monitoring, as well as no specific antidote will be required. Ribo is the first company in the world that brings forward such an FXI-targeting GalNAc-siRNA molecule, and is currently in Phase 1 clinical testing.
A novel GalNAc-siRNA conjugate targeting Apolipoprotein CIII (ApoC3) with best-in-class potential (RBD5044)
Hypertriglyceridemia is one of the most important dyslipidemia diseases, which causes endothelial dysfunction, accelerates the initiation and progression of atherosclerosis, and increases the risk of acute pancreatitis. Targeting APOC3 through the siRNA mechanism is believed to achieve long-lasting and efficient reduction of plasma triglyceride, as well as ApoB-containing lipoproteins in patients, which in turn will be cardioprotective for patients with atherosclerotic cardiovascular diseases. RBD5044 is currently at the Phase 1 clinical stage. IND-enabling safety and efficacy data was shown at the conference and demonstrated potential class-leading efficacy and duration.
Improvement of cardiac remodeling and blood pressure by targeting liver angiotensinogen (AGT) with GalNAc-siRNA – a RNAi molecule with best-in-class potential (R0797070)
In addition to the two siRNA products in clinical stage, Ribo also presented long-term preclinical efficacy data from an angiotensinogen silencing GalNAc-siRNA program. The preclinical data shows efficient inhibition of hepatic AGT expression, leading to sustained reduction of blood pressure, and a significant improvement in left ventricular hypertrophy, the efficacy also demonstrated partially blood pressure independent mechanism compared with Captopril. Taken together, Ribos AGT drug candidate is anticipated to provide superior blood pressure control in patients with resistant hypertension, as well as bringing additional cardioprotective benefits. The product is about to start the IND-enabling work and will also explore new indications beyond hypertension in upcoming clinical trials.
”It is fascinating to see from the congress that RNAi-based therapies are entering the cardiology for real, both in the primary and secondary prevention setting especially when it comes to chronic diseases. Also, it is increasingly evident, by specifically targeting the liver, we can treat a wide range of cardiovascular diseases, including lipid and coagulation disorders, hypertension, as well as heart failure. With our rich pipeline and extensive capacity build in this area, our confidence and dedication are greater than ever to accelerate development of these promising projects to benefit patient in need worldwide.” says Dr. Li-ming Gan, Global R&D President and Co-CEO of Suzhou Ribo Life Science, and CEO at Ribocure Pharmaceuticals AB.