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Arrowhead presents preclinical data on expanding cardiometabolic pipeline.

Arrowhead Pharmaceuticals announced the presentation of new preclinical data on its expanding pipeline of RNA interference therapeutics for cardiometabolic diseases, including ARO-ANG3, which targets angiopoietin-like protein 3, and ARO-APOC3, which targets apolipoprotein C-III. The invited lecture, titled "The promise of RNA interference as a therapeutic approach for treatment of cardiovascular diseases," was presented at the Vascular Discovery: From Genes to Medicine - Scientific Sessions 2018, a symposium organized by the American Heart Association. Arrowhead intends to file clinical trial applications (CTA) for ARO-ANG3 and ARO-APOC3 before the end of 2018. In the presentation, Dr. Given discussed the recent progress achieved using RNA interference as a therapeutic modality for the development of new drugs to treat cardiovascular diseases. The new preclinical data presented on ARO-APOC3 and ARO-ANG3 included the following:: A single 2 mg/kg dose of ARO-APOC3 in ApoC3 transgenic mice led to the following observations: Serum ApoC3 levels were reduced by approximately 90%, maximum knockdown was sustained for over three weeks. the lipid profiles improved with large reductions in serum triglycerides and cholesterol and large increases in HDL and in dose ranging studies of ARO-ANG3 in wild type mice, reductions in serum ANGPTL3 and liver mRNA were similar, indicating that the observed knockdown of serum ANGPTL3 is a direct result of the expected RNAi effect. The following mouse disease models were also interrogated: LDL receptor knock-out mice, leptin receptor defective db/db mice and diet-induced obese mice. A single 3 mg/kg dose in LDLr-/- mice and in db/db mice led to: a maximum reduction of ANGPTL3 of 98% and substantial decreases in serum triglycerides and LDL. A single 3 mg/kg dose in DIO mice led to: a maximum reduction of ANGPTL3 of 99.7% and approximately 50-60% reductions in serum triglycerides and LDL.

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Publication:The Fly
Date:May 11, 2018
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