On July 12th, 2024, Sirnaomics Ltd. ("Company", stock code: 2257.HK, along with its affiliated companies, collectively referred to as "Group" or "Sirnaomics", a leading biopharmaceutical company dedicated to exploring and developing RNAi therapies) announced today that the Group has completed the IND preparatory study of STP125G, an siRNA therapeutic drug targeting lipoprotein C3 (ApoC3), based on its proprietary GalAhead mxRNA technology. The safety and efficacy results of non-human primate (NHP) studies strongly support the Group's application for IND to the US FDA to initiate a Phase I clinical trial of STP125G for cardiovascular indications.
Lipoprotein C3 plays an important role in triglyceride metabolism and is recently considered a multifunctional modulator that regulates lipid metabolism through various pathways outside lipid metabolism by affecting cardiovascular, metabolic, and nervous system disease risks. Studies have shown that high levels of triglycerides (TG) are associated with an increased risk of cardiovascular disease. For patients with severe hypertriglyceridemia (sHTG) with triglyceride levels exceeding 1000 mg/dL, the risk of developing acute pancreatitis is 5 to 10 times that of the general population. The use of siRNA or antisense oligonucleotides to downregulate lipoprotein C3 has been shown to effectively reduce triglycerides in patients with severe hypertriglyceridemia.
During the efficacy evaluation of STP125G using non-human primate models (N = 4), we observed dose-dependent silencing activity at doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg, which also had high safety. The 10 mg/kg dose reached the maximum target silencing effect at around the fourth week and lasted for 9 weeks (a 13-week study period). Safety evaluation of STP125G using non-human primate models (N = 4) showed that a single subcutaneous injection of doses of 50 mg/kg, 100 mg/kg, or 250 mg/kg had excellent safety. The maximum target silencing effect of all three high doses was comparable to the 10 mg/kg level.
Dr. Patrick Y. Lu, Founder, Chairman of the Board, Executive Director, President and CEO of Sirnaomics, stated, "STP125G is our second candidate drug based on our GalAhead mxRNA technology, which has shown excellent safety and strong efficacy in non-human primate models. Compared with antisense nucleotides and other siRNA drugs, the long-lasting silencing activity of STP125G on lipoprotein C3 can bring better therapeutic effects for patients with cardiovascular disease. These test results further validate that STP125G is a new type of siRNA candidate drug that can use our proprietary GalAhead-based delivery technology to treat hypertriglyceridemia and other cardiovascular diseases."