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Pre-clinical Results with RNAi Therapeutics for Cardiovascular Metabolic Disease at ATVB 2014

We have presented new pre-clinical data from our growing pipeline of RNAi therapeutics for the treatment of cardiovascular metabolic disease, including ALN-PCSsc targeting PCSK9 for the treatment of hypercholesterolemia, and a newly named program, ALN-AC3 targeting apolipoprotein C-III (apoCIII) for the treatment of hypertriglyceridemia.  The data were presented in an oral presentation at the Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) 2014 Scientific Sessions held May 1-3, 2014 in Toronto, Ontario.



New data in non-human primates demonstrated that a single dose of ALN-PCSsc significantly reduced plasma PCSK9 protein by up to 96%, with mean PCSK9 knockdown at nadir of 88% at the top dose.  Results also showed lowering of LDL-C of up to 77%, with a mean reduction of 69% at the top dose.  These results were observed in the absence of statin co-administration.  In addition, knockdown of PCSK9 and lowering of LDL-C were rapid and durable, with maximal effects lasting greater than 90 days and returning to baseline at approximately 160 days.  At the top dose, an over 50% reduction in LDL-C was maintained for over 90 days.  These data support a once-monthly and possibly a once-quarterly subcutaneous dosing regimen, which represents what should be a highly competitive profile with anti-PCSK9 monoclonal antibodies.  We plan to advance ALN-PCSsc, which is partnered with The Medicines Company, toward clinical trials by the end of this year or early next.

In addition, we presented rodent data with ALN-AC3 – our newly named GalNAc-siRNA conjugate targeting apoCIII – showing up to 95% knockdown of apoCIII and up to 68% reduction in triglycerides.  These results warrant further efforts to advance this new RNAi therapeutic program into later stages of development.