Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has presented new pre-clinical data from RNAi therapeutic programs toward genetically validated targets in cardiovascular metabolic diseases, 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. These data are being presented at the Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) 2014 Scientific Sessions being held May 1-3 in Toronto, Ontario. In an oral presentation titled “ A Subcutaneous, Potent and Durable RNAi Platform Targeting Metabolic Diseases, Genes PCSK9, ApoCIII and ANGPLT3” new pre-clinical data utilizing the company’s GalNAc-siRNA conjugate platform demonstrated robust and durable knockdown of these key cardiovascular metabolic disease targets. Amongst other data, Alnylam presented new single-dose durability data for ALN-PCSsc showing robust knockdown of PCSK9 and reductions in LDL-C that support once-monthly and possibly once-quarterly subcutaneous dosing regimens. Specifically, a single dose of ALN-PCSsc maintained greater than 50% LDL-C reductions for over three months in the absence of statin co-administration. The company plans to file an investigational new drug (IND) application, or IND equivalent, for ALN-PCSsc by late 2014 or early 2015.
“As evidenced by these data presented at ATVB, we are building the beginnings of a promising pipeline of RNAi therapeutics toward genetically validated disease targets in the cardio-metabolic space. We see this as an attractive area for continued investment for Alnylam given the large number of liver-expressed disease-causing genes and the emerging profile of our GalNAc-conjugate platform enabling subcutaneous delivery with potent disease gene knockdown, a wide therapeutic index, and highly durable effects. These features are exemplified with ALN-PCSsc, where new non-human primate pre-clinical results demonstrate significant knockdown of PCSK9 and reductions in LDL-C with very durable effects, lasting over three months. We believe that this level of durability should readily support a once-monthly and possibly a once-quarterly subcutaneous dosing regimen, and thus represents what should be a highly competitive profile with anti-PCSK9 monoclonal antibodies. We look forward to advancing ALN-PCSsc toward clinical trials by the end of this year or early next,” said Kevin Fitzgerald, Ph.D., Senior Director, Research at Alnylam. “In addition, new rodent data with ALN-AC3, our GalNAc-siRNA conjugate targeting apoCIII, showed up to 95% knockdown of ApoCIII and up to 68% reduction in triglycerides. These pre-clinical results warrant further efforts to advance this new RNAi therapeutic program into later stages of development.”