Sirnaomics Completes IND-Enabling Studies for STP125G Targeting ApoC3 in Cardiovascular Treatment

July 12, 2024  -- Sirnaomics Ltd. (Stock Code: 2257.HK), a premier biopharmaceutical company, announced the completion of IND-enabling studies for their siRNA therapeutic candidate, STP125G. This groundbreaking drug targets Apolipoprotein C3 (ApoC3) using Sirnaomics' unique GalAhead™ mxRNA technology. The non-human primate (NHP) study results have paved the way for an IND filing with the U.S. FDA to start Phase I clinical trials for cardiovascular disease treatments.

Apolipoprotein C3 (ApoC3) is a crucial element in triglyceride metabolism and has implications in various pathways influencing cardiovascular, metabolic, and neurological risks. Elevated triglyceride (TG) levels are linked to a higher likelihood of cardiovascular diseases. For individuals with severe hypertriglyceridemia (sHTG), with TG levels exceeding 1000 mg/dL, the risk of acute pancreatitis is significantly higher. Reducing ApoC3 via siRNA or antisense oligonucleotides has been effective in lowering TG levels in such patients.

During the efficacy assessment of STP125G in an NHP model (N = 4), a dose-dependent silencing activity was observed across 1 mg/kg, 3 mg/kg, and 10 mg/kg doses, exhibiting a robust safety profile. The maximum silencing effect was seen at 10 mg/kg by the fourth week and sustained for another nine weeks. Safety evaluations using an NHP model (N = 4) showed excellent results with a single subcutaneous dose of 50 mg/kg, 100 mg/kg, or 250 mg/kg. These doses displayed similar maximum target silencing efficacies as the 10 mg/kg dosage.

"STP125G is our second drug candidate using the GalAhead™ mxRNA technology, demonstrating remarkable safety and efficacy in NHP models. Its prolonged silencing effect against ApoC3 could offer a better therapeutic option for cardiovascular patients compared to existing antisense and siRNA drugs," stated Dr. Patrick Lu, Founder, Chairman, Executive Director, President, and CEO of Sirnaomics. "These data reaffirm STP125G as a pioneering siRNA therapeutic candidate for hypertriglyceridemia and other cardiovascular conditions using our proprietary GalAhead™ delivery technology."

ApoC3 is emerging as a key target linking hypertriglyceridemia with cardiovascular diseases (CVD). It modulates several established CVD risk factors and is found on chylomicrons, VLDL, LDL, and HDL particles. Studies have shown that ApoC3 levels are an independent CVD risk factor, potentially promoting the atherogenicity of lipoproteins. ApoC3 is also involved in HDL metabolism and may contribute to atherosclerosis, inflammation, and ER stress in endothelial cells. Additionally, it plays a role in insulin resistance, lipodystrophy, diabetic dyslipidemia, and postprandial hypertriglyceridemia (PPT).

The involvement of ApoC3 in Alzheimer's disease pathogenesis suggests that modifying its levels could slow disease progression. It is also linked to cardiovascular disease risk, coronary artery disease progression, and aortic valve calcification. Inhibiting ApoC3 has been identified as a promising strategy to manage hypertriglyceridemia and prevent CVD. The role of ApoC3 in multiple cardio-metabolic pathways reinforces its significance. STP125G, a single-stranded siRNA therapeutic targeting ApoC3 mRNA, leverages Sirnaomics' GalAhead™ mxRNA technology.

Sirnaomics is dedicated to discovering and developing RNA therapeutics for unmet medical needs. It is the first clinical-stage RNA therapeutics company with a strong presence in both Asia and the United States. Utilizing proprietary delivery technologies, Sirnaomics has built an extensive drug candidate pipeline. STP122G, the initial drug candidate using GalAhead™ mxRNA technology, is in Phase I development. STP125G, the second siRNA therapeutic targeting ApoC3 mRNA, focuses on cardiovascular disease treatment. STP237G, the first dual-targeted drug based on GalAhead™ muRNA technology, is in the late preclinical evaluation stage. Sirnaomics has also advanced oncology applications through its clinical programs for STP705 and STP707, transitioning from a biotech firm to a biopharma corporation.

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