�Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics caller, announced that new presymptomatic data from its hypercholesterolemia program was published in Proceedings of the National Academy of Sciences (Frank-Kamenetsky, M., et al (August 11, 2008) Proc. Natl Acad. Sci. USA, 10.1073/pnas.0805434105). The promulgated, peer-reviewed information demonstrate for the offset time that a chemically synthesized minuscule interfering RNA (or siRNA, the molecules that mediate RNAi) targeting the factor proprotein convertase subtilisin/kexin type 9 (PCSK9) achieves acute and undestroyable lowering of total cholesterol levels in both mice and rats, and LDL cholesterol levels in nonhuman primates. Human genetic studies have correlative increased levels of PCSK9 with an increased risk of cardiovascular disease (Abifadel et al., Nature Genetics, 34 (2): 154-6; 2003). Conversely, human genetic studies have confirmed a most 88 per centum reduced risk of exposure of cardiac events in subjects with decreased levels of PCSK9 (Cohen et al., New England Journal of Medicine, 354: 1264-72; 2006).
The new inquiry, conducted by Alnylam scientists in coaction with scientists at UT Southwestern Medical Center in Dallas, Alnylam Europe (straightaway Roche Kulmbach), and the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, demonstrated in vivo efficaciousness for an RNAi sanative targeting PCSK9 in mice, rats, and non-human order Primates.
Specifically, the data showed:
- potent silencing of PCSK9 mRNA in mouse, rat, nonhuman primate, and in a transgenic model expressing human PCSK9;
- highly selective silencing of the PCSK9 messenger RNA (mRNA) by PCSK9 specific siRNAs as compared with unrelated siRNA controls and want of induction of INF? and TNF? by chemically modified siRNA compounds;
- proof of an RNAi mechanism of action as driven by 5'-RACE measurements;
- acute onset of action and long durability of biologic effect with reductions in total cholesterin levels in rodents and LDL cholesterin in order Primates observed by 48 to 72 hours that lasted 2 to 3 weeks after a single judicature;
- mechanistic rationale for cholesterin lowering as demonstrated by reduction in PCSK9 plasma protein levels and a concomitant addition in LDL-receptor levels in liver;
- therapeutic efficacy as measured by significant reductions in LDL-cholesterol levels by up to 60 pct of pre-dose levels in nonhuman primates; and,
- tolerability as analyzed by legion measurements including liver triglyceride levels with no statistical differences discovered between handling versus control groups.
Partial results of this study were antecedently presented at the XVI International Symposium on Drugs Affecting Lipid Metabolism in October 2007.
"We are very bucked up by the significance of these findings, including information in nonhuman primates, which continue to validate PCSK9 as an attractive aim for a systemic RNAi therapeutic approach given its ability to achieve acute and indestructible reductions in LDL cholesterin," said Victor Kotelianski, M.D., Ph.D., Vice President of Research at Alnylam. "PCSK9 is well validated based on human genetics, simply it has been a difficult protein to objective using traditional drug discovery modalities, such as small molecules and monoclonal antibodies. Thus, RNAi affords mayhap the only viable approaching for new medicines targeting this key mechanism for control of LDL metamorphosis."
"There is a clear unmet medical need for novel agents that john lower LDL cholesterol, and PCSK9 appears to be an fantabulous, genetically validated target for disease intervention," said Jay Horton, M.D., Professor of Internal Medicine and Molecular Genetics, UT Southwestern Medical Center. "Based on its novel mechanism of activeness and presymptomatic data to date, an RNAi remedial targeting PCSK9 has the potential to rapidly lour LDL cholesterin, while mayhap functioning synergistically with statins in the treatment of hypercholesterolemia."
Alnylam is developing ALN-PCS, an RNAi therapeutical targeting PCSK9, for the treatment of hypercholesterolemia; ALN-PCS is a systemically delivered RNAi therapeutical comprised of an optimized siRNA encapsulated in a liposomal nanoparticle formulation.
About PCSK9
PCSK9 is an important cistron involved in the metamorphosis of LDL cholesterol. The normal part of the PCSK9 protein is to break down the cellular phone surface receptor for LDL; when thither is less PCSK9 protein, there is more sensory receptor on the cell surface to remove LDL cholesterol from the bloodstream. In human studies, mutant forms of PCSK9 that take increased activity are linked with a familial form of hypercholesterolemia. Conversely, recent research published in the New England Journal of Medicine (Cohen et al., New England Journal of Medicine, 354: 1264-72; 2006) has demonstrated that former mutations in humans, including those that lower PCSK9 function, ar associated with decreased LDL cholesterol levels and an 88 percentage risk diminution in cardiovascular disease.
About RNA Interference (RNAi)
RNAi (RNA encumbrance) is a revolution in biology, representing a breakthrough in sympathy 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 one time every decennium or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug find 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 biologic process of RNAi occurring in our cells, the creation of a major new course of instruction of medicines, known as RNAi therapeutics, is on the purview. RNAi therapeutics target the cause of diseases by potently silencing specific courier RNAs (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 curative expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the stream 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 ripe program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide kitchen stove of disease areas, including liver cancers, hypercholesterolemia, and Huntington's disease. The company's leadership position in rudimentary patents, applied science, and know-how relating to RNAi has enabled it to signifier major alliances with preeminent companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, and Kyowa Hakko Kogyo. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established "RNAi 2010" which includes the s be after to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to mannikin four or more new major line collaborations, all by the end of 2010. Alnylam is a joint proprietor of Regulus Therapeutics LLC, a joint venture focused on the discovery, growing, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit http://www.alnylam.com.
Alnylam Forward-Looking Statements
Various statements in this sack concerning Alnylam's future expectations, plans and prospects, appoint forward-looking statements for the purposes of the safe harbor commissariat under The Private Securities Litigation Reform Act of 1995. Actual results whitethorn differ materially from those indicated by these modern statements as a consequence of versatile important factors, including risks related to: Alnylam's approach to discover and acquire novel drugs, including ALN-PCS, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam's ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third base parties; Alnylam's ability to obtain additional funding to support its business activities; Alnylam's ability to understand future milestones and royalties as well as co-development and co-commercialization opportunities; Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory favourable reception for products; competition from others using technology like to Alnylam's and others developing products for similar uses; Alnylam's dependence on collaborators; and Alnylam's unforesightful operating history; as well as those risks more fully discussed in the "Risk Factors" section of its to the highest degree recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In gain, any advanced statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does non assume any obligation to update any forward-looking statements.
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