New pre-clinical data from Alnylam Pharmaceuticals' ALN-VSP program presented

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced new pre-clinical data from its ALN-VSP program presented at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics International conference being held November 15 - 19, 2009 in Boston, Mass. ALN-VSP is an RNAi therapeutic currently in a Phase I clinical trial for the treatment of liver cancers, including hepatocellular carcinoma (HCC) and other solid tumors with liver involvement. The new data demonstrated robust anti-tumor activity in orthotopic liver tumor models comprised of both HCC- and colorectal cancer-derived cell lines. ALN-VSP was also shown to act on disseminated tumors outside of the liver. Further, in addition to anti-proliferative effects, studies showed that ALN-VSP exerts a potent anti-angiogenic effect on tumors.

“ALN-VSP is Alnylam’s first systemic RNAi program, as well as our first clinical program in an oncology indication,” said Dinah Sah, Ph.D., Vice President Research, CNS and Oncology at Alnylam. “This RNAi therapeutic targets two well-validated genes critical for tumor cell proliferation and survival, an attractive strategy supported by these current data for the advancement of novel anti-cancer medicines. Meanwhile, we are making continued progress in our Phase I clinical trial with ALN-VSP having now enrolled a significant portion of the study across multiple dose cohorts, and look forward to sharing preliminary results in mid-2010.”

ALN-VSP is an RNAi therapeutic comprised of two small interfering RNAs (siRNAs) formulated in a lipid nanoparticle (LNP) and designed to target two genes critical in the growth and survival of cancer cells: kinesin spindle protein, or KSP, required for tumor cell proliferation; and vascular endothelial growth factor, or VEGF, required for blood vessel formation to sustain tumor growth. The pre-clinical studies were performed using ALN-VSP in an orthotopic liver tumor model utilizing either human HCC cells or human colorectal carcinoma cells. In a poster titled “Development of ALN-VSP: an RNAi Therapeutic for Liver Malignancies,” Alnylam scientist Dr. Iva Toudjarska, presented the following data:

• ALN-VSP-mediated silencing of KSP in both HCC and colorectal carcinoma models, resulting in the accumulation in tumor cells of aberrant mitotic figures, also known as monoasters, a hallmark of KSP inhibition;
• monoaster formation in tumor cells within lymph node metastases derived from the orthotopic liver tumors, demonstrating the ability of LNPs in general, and ALN-VSP in particular, to achieve effective delivery in extra-hepatic tumor sites;
• marked anti-angiogenic effects resulting from ALN-VSP treatment, including reductions in both tumor microvessel density and intratumoral hemorrhage; and
• similar anti-angiogenic results with an LNP containing only the VEGF siRNA, demonstrating that the vascular effects are due to VEGF silencing.

“We are very encouraged by these new results, as they show anti-tumor activity for ALN-VSP in both primary and metastatic disease settings,” said David Bumcrot, Ph.D., Director, Research at Alnylam. “Importantly, these new studies demonstrate anti-tumor activity in extra-hepatic tumors, highlighting the potential for effective delivery of siRNAs to sites beyond the liver. These new results also confirm the anti-angiogenic effects of ALN-VSP, providing continued support for our dual-targeting strategy.”

ALN-VSP is currently in a Phase I multicenter, open-label, dose-escalation trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALN-VSP in patients with advanced solid tumors with liver involvement, including HCC. Alnylam has enrolled a significant number of patients across multiple dose cohorts in the Phase I trial, and expects to present preliminary data from the Phase I trial in mid-2010. ALN-VSP is formulated in an LNP, also known as SNALP, in collaboration with Tekmira Pharmaceuticals Corporation.