Alnylam Pharmaceuticals, Inc. has announced at the American Association for Cancer Research (AACR) 2007 Annual Meeting that it will advance a systemically delivered RNAi therapeutic, ALN-VSP01, for the treatment of liver cancer and potentially other solid tumors as a new development program.
ALN-VSP01 is an RNAi therapeutic that is designed to target vascular endothelial growth factor (VEGF) and kinesin spindle protein (KSP), two well-validated genes that are involved in distinct pathways of tumor pathology, cell proliferation and angiogenesis, in a wide variety of cancers.
Alnylam expects to submit an investigational new drug (IND) application for this program in 2008.
“We believe that there is real potential to develop an RNAi therapeutic for the treatment of liver cancer based on our encouraging progress with systemic delivery of siRNAs toward liver-expressed target genes,” said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam.
“Primary liver cancer is the world’s most common solid tumor type and is associated with one of the poorest survival rates in cancer. Our encouraging pre-clinical data demonstrate the ability of siRNAs to silence two well-validated genes critical for tumor proliferation and survival, and our strategy of using an RNAi therapeutic that targets these two distinct pathways is aimed at increasing the likelihood of achieving meaningful clinical benefit for patients,” he continued.
Data announced during a symposium titled “RNAi Therapies” at AACR showed the ability of RNAi therapeutics to silence both VEGF and KSP expression in the liver and to stop cancer cell proliferation by targeting KSP.
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 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.