( a rodent model; -- Silencing of KSP ...)Alnylam Announces Advancement of a New RNAi Therapeutic Development,Program for the Treatment of Liver Cancer,Health

-- Silencing of KSP mRNA in vivo by greater than 50 percent after a single injection of a KSP-specific siRNA in a rodent model; and

-- Halting of human cancer cell proliferation in vitro when KSP was silenced by a target-specific siRNA.

Alnylam's RNAi therapeutic, ALN-VSP01, is comprised of two small interfering RNAs, or siRNAs, the molecules that mediate RNAi. Each siRNA targets a distinct and well-validated gene in the growth and proliferation of tumors: VEGF, a key mediator of tumor angiogenesis; and KSP, a protein required for cell division that, when inhibited, leads to cell arrest and cell death in dividing cells. ALN-VSP01 is formulated using Alnylam's novel liposomal formulation technology, which has been used to achieve delivery of siRNAs to cells of the liver and efficient silencing of genes expressed in that organ. Liposomal delivery can also be optimized for delivery to other organs and tumor types, such that ALN-VSP01 may ultimately have potential for a range of solid tumors. Alnylam's collaborator, Inex Pharmaceuticals Corporation, is manufacturing the lipid-based formulation as the company prepares for pre-IND toxicology studies with ALN-VSP01.

"Despite many advances in the treatment of cancer with targeted small molecules and antibody therapeutics, the clinical impact of these therapies is generally measured in only months of survival benefit. New modalities like RNAi therapeutics offer the potential to advance cancer therapy to a whole new level," said George D. Demetri, M.D., of Dana-Farber Cancer Institute and Harvard Medical School. "I'm encouraged by Alnylam's pre-clinical data demonstrating the ability to silence disease pathway genes with delivery of RNAi therapeutics, and believe that the application of this approach for the treatment of primary and secondary liver cancers holds considerable promise."

About Liver Cancer

Primary liver cancer is cancer that forms in the tissues of the l
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