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Alnylam Scientists Present New Research on Expanded Delivery of RNAi Therapeutics

^{Published on 2010-10-08 08:28:51 - Market Wire}
 

CAMBRIDGE, Mass.--([ BUSINESS WIRE ])--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company presented new pre-clinical research today at the 8^th International M. Judah Folkman Conference, New Frontiers in Therapeutic Development, held October 8-9, 2010 in Cambridge, Mass, highlighting significant advances in the systemic delivery of RNAi therapeutics. The new research demonstrated effective silencing of target genes in distinct cell types and tissues beyond the liver with systemic delivery of RNAi therapeutics. In particular, novel lipid nanoparticles (LNPs) were designed in collaboration with the laboratory of Daniel Anderson, Ph.D. at the Massachusetts Institute of Technology (MIT) to deliver siRNAs to the vascular endothelium, the cells that line blood vessels throughout the body. RNAi-mediated target gene silencing was observed in endothelial cells across a broad range of tissues, with duration of action lasting for over two months after a single dose. Delivery to the vascular endothelium creates new RNAi therapeutic approaches in disease areas including atherosclerosis, diabetes, inflammation, and cancer. Additional new results were also presented regarding delivery of RNAi therapeutics to immune cells.

"a major scientific breakthrough that happens once every decade or so"

aOne of our key achievements over the past 12 months is the major progress we and our collaborators have made in advancing systemic delivery of RNAi therapeutics. In this regard, we have already shown markedly improved potency of RNAi therapeutics, with in vivo gene silencing at single microgram per kilogram doses, in addition to broadened activity that includes tumors and immune cells,a said Kevin Fitzgerald, Ph.D., Senior Director, Research. aAmongst other data presented at this meeting, we are pleased to now report the discovery of novel LNPs that enable RNAi-mediated silencing of target genes in endothelial cells across a wide variety of vascular tissues, with duration of silencing lasting over two months after a single dose. These new data continue to exemplify Alnylama™s leadership in delivery, a critical determinant in bringing RNAi therapeutics to patients as a whole new class of innovative medicines.a

This new work showed that potent siRNAs designed toward Tie2 a" an endothelium-specific receptor-like tyrosine kinase a" formulated in a novel LNP achieved dose dependent silencing of Tie2 mRNA. This in vivo efficacy was observed in a broad range of tissues including liver, heart, intestine, spleen, and skeletal muscle, reflecting silencing of the Tie2 mRNA in the vascular endothelium of these tissues. Tie2 mRNA silencing was also found to be durable, lasting more than two months after a single dose administration.

In addition, new data were presented regarding immune cell delivery, where up to 95% silencing of the target gene CD45 was achieved in immune cells with an ED₅₀ of 0.2 mg/kg. RNAi-mediated immune cell gene silencing was observed in multiple species and was found to be durable for approximately one month after a single dose.

Systemic delivery remains one of the most important objectives in advancing RNAi therapeutics as a new class of medicines to patients. In particular, LNPs represent a promising approach for delivery of siRNAs with robust therapeutic efficacy now reported across a broad range of cell types, tissues, and species. Alnylam is currently enrolling patients in two separate Phase I clinical programs with systemically delivered RNAi therapeutics, including ALN-VSP for the treatment of liver cancers and ALN-TTR01 for the treatment of transthyretin (TTR)-mediated amyloidosis (ATTR). Both ALN-VSP and ALN-TTR01 utilize a first generation LNP formulation and are developed in collaboration with Tekmira Pharmaceuticals Corporation. In addition, Alnylam is advancing second-generation LNPs with improved efficacy in its ALN-PCS and ALN-TTR02 programs. Additional systemic delivery approaches under development at Alnylam include siRNA conjugates, mimetic lipoprotein particles (MLPs), amongst other strategies under investigation.

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 aa major scientific breakthrough that happens once every decade or so,a 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 Alnylama™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 worlda™s top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics for the treatment of a wide range of disease areas, including respiratory syncytial virus (RSV), liver cancers, TTR-mediated amyloidosis (ATTR), hypercholesterolemia, and Huntingtona™s disease. In addition, Alnylam formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in manufacturing processes for biotherapeutic products, including recombinant proteins and monoclonal antibodies. The companya™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. Alnylam and Isis are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit [ www.alnylam.com ].

Alnylam Forward-Looking Statement

Various statements in this release concerning Alnylama™s future expectations, plans and prospects, including without limitation, its expectations regarding the development of effective and efficient delivery approaches for RNAi therapeutics, including through the discovery of novel technologies such as lipid nanoparticles for systemic delivery of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including Alnylama™s ability to continue the development of effective and efficient delivery approaches for RNAi therapeutics, and discover and develop novel drug candidates, including systemically delivered drug candidates formulated in novel lipid nanoparticles, as well as those risks more fully discussed in the aRisk Factorsa section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylama™s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.