Alnylam Pharmaceuticals, Inc, a leading RNAi therapeutics company, announced that it has submitted an investigational new drug (IND) application to the US Food and Drug Administration (FDA) for ALN-VSP, an RNAi therapeutic for the treatment of liver cancers, including hepatocellular carcinoma and other solid tumours with liver involvement. ALN-VSP contains two small interfering RNAs (siRNAs), the molecules that mediate RNAi, formulated in a lipid nanoparticle developed by Tekmira Pharmaceuticals Corporation.

ALN-VSP is designed to target two genes critical in the growth and development of cancer: kinesin spindle protein, or KSP, required for tumour proliferation; and vascular endothelial growth factor, or VEGF, required for tumour growth. Pre-clinical data in mouse tumour model studies have demonstrated robust efficacy of ALN-VSP, including suppression of these targeted genes, demonstration of an RNAi mechanism of action, tumour reduction, and extension of survival.

"ALN-VSP represents Alnylam's first IND for a systemically delivered RNAi therapeutic, which is a testament to the very strong progress we've made in achieving systemic delivery of siRNAs, including our efforts with Tekmira," said Akshay Vaishnaw, M.D., Ph.D., senior vice president, clinical research at Alnylam. "We're also pleased, with this IND filing, to have met one of our key pipeline goals for 2008. Following FDA review of our submission, we expect to initiate patient dosing in the first half of 2009, which positions us solidly on track to meet our goal of having three programs in clinical trials next year."

"Based on the encouraging pre-clinical data we've seen to date with this programme, we believe our strategy of using an RNAi therapeutic targeting Two well-validated genes critical for tumour proliferation and survival has the potential of achieving meaningful clinical benefit for patients with liver cancer," said Dinah Sah, Ph.D., vice president, Research, CNS and Oncology, at Alnylam. "We believe that this is the first dual targeting RNAi therapeutic program to advance to this stage of development across the entire industry. This is an important milestone, as we view the ability to design and formulate siRNAs that achieve dual targeting as a very attractive feature of our RNAi therapeutics platform, especially in the setting of oncology drug discovery."

"Cancer affecting the liver, either as primary disease or as metastatic spread from cancer originating at another site, represents a major cause of death and a major unmet medical need affecting a large number of patients in the U.S. and across the world," said George D. Demetri, M.D., director of the Ludwig Center at Dana-Farber Cancer Institute and Harvard Medical School, a collaborating investigator in this work. "Many common cancers, such as breast cancer and colorectal cancer, spread to the liver, where the metastatic disease is life threatening. Additionally, primary liver cancer, known as hepatocellular carcinoma, is one of the most common solid tumours in the world overall, and is associated with one of the poorest survival rates in cancer. The ALN-VSP clinical development programme will have great impact in this area, if the pre-clinical testing can be translated into similar benefits for patients with liver involvement from cancer."

The proposed Phase I study is a multi-centre, open label, dose escalation trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous ALN-VSP in patients with advanced solid tumours with liver involvement. Additional study design details will be provided upon initiation of the Phase I trial.

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs.