Alnylam Presents New Pre-clinical Data on ALN-VSP, an RNAi Therapeutic for the Treatment of Liver Cancer

New Results Demonstrate Robust Anti-Tumor Activity in Multiple Models, Including Extra-Hepatic Tumors

CAMBRIDGE, MA, USA | November 18, 2009 | 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.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

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. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world’s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection and is partnered with Cubist and Kyowa Hakko Kirin. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, Huntington’s disease, and TTR amyloidosis. The company’s leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam established “RNAi 2010” in January 2008 which includes the company’s plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit

SOURCE: Alnylam Pharmaceuticals

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