Alnylam Announces Collaboration with University of Texas Southwestern Medical Center to Discover RNAi Therapeutics for Hypercholesterolemia; Collaboration to Focus on PCSK9, a Key Gene Involved in Metabolism of LDL-Cholesterol

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Alnylam Announces Collaboration with University of Texas Southwestern Medical Center to Discover RNAi Therapeutics for Hypercholesterolemia; Collaboration to Focus on PCSK9, a Key Gene Involved in Metabolism of LDL-Cholesterol
July 17, 2006
Alnylam
CAMBRIDGE, Mass.--(BUSINESS WIRE)--July 17, 2006--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has entered into a collaboration with University of Texas (UT) Southwestern Medical Center at Dallas to evaluate new approaches for reducing LDL-cholesterol levels using RNAi therapeutics directed to a disease target called proprotein convertase subtilisn/kexin type 9, or PCSK9.
"It is very exciting for us to be partnering with UT Southwestern Medical Center, one of the world's leading academic centers in the area of cholesterol metabolism," said Victor Kotelianski, M.D., Ph.D., Vice President of Research for Alnylam Pharmaceuticals. "PCSK9 is a compelling target for potential breakthrough treatments of hypercholesterolemia and complications of acute coronary syndromes. Although PCSK9 is validated based on human genetics, it has been a difficult protein to target using traditional drug discovery approaches. Therefore, we believe it is an ideal target for a systemic RNAi approach in light of our recent progress with systemic delivery of RNAi therapeutics."
PCSK9 is an important gene involved in the metabolism of LDL-cholesterol, or so-called "bad cholesterol." The normal role of the PCSK9 protein is to break down the LDL receptor (LDL-R); when there is less PCSK9 protein, there is more LDL-R on the cell surface. Research at UT Southwestern Medical Center has shown that reductions in the levels of PCSK9 protein can lead to significant reductions of LDL in the blood, and in fact mice lacking PCSK9 have significantly decreased cholesterol with no other adverse phenotype.
The collaboration will utilize systemic RNAi technologies developed by Alnylam such as those described in its recent Nature paper in primates (Nature 441: 111-114, 2006) where systemic RNAi targeting apolipoprotein B (apoB), another protein involved in cholesterol metabolism, resulted in dramatically reduced levels of apoB mRNA and protein and resulted in a greater than 65 percent lowering of cholesterol and a greater than 85 percent lowering of LDL.
"We believe PCSK9 is an excellent target for the potential development of RNAi therapeutics based on data from human genetic studies, and this approach holds significant promise for controlling LDL-cholesterol levels in humans," said Jay Horton, M.D., Associate Professor of Internal Medicine and Molecular Genetics, UT Southwestern Medical Center. "I have been impressed with Alnylam's ability to silence disease-causing genes with RNAi as evidenced in their 2006 Nature paper and look forward to working with them to evaluate an RNAi approach targeting PCSK9."
Human mutations in PCSK9 that increase PCSK9 activity are linked with an autosomal dominant form of hypercholesterolemia. In turn, recent research published in the New England Journal of Medicine (N. Engl. J. Med. 354, 1264-1272, 2006) has demonstrated that human polymorphisms that lower PCSK9 function are associated with an 88 percent risk reduction in coronary heart disease. PCSK9 is also known to be increased in expression in the presence of statin therapy, perhaps explaining resistance mechanisms for statin therapy in certain patient populations.
About RNA Interference (RNAi)
RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing.
About Alnylam
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 building a pipeline of RNAi therapeutics; its lead program is in Phase 1 human clinical trials for the treatment of respiratory syncytial virus (RSV) infection, which is the leading cause of hospitalization in infants in the U.S. 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 Merck, Medtronic, and Novartis. The company, founded in 2002, maintains global headquarters in Cambridge, Massachusetts, and has an additional operating unit in Kulmbach, Germany. Alnylam is honored to be the "emerging/mid-cap" company recipient of the 2006 James D. Watson Helix Award, the biotechnology industry's award for outstanding achievement. For more information, visit www.alnylam.com.
About UT Southwestern Medical Center
UT Southwestern Medical Center at Dallas, one of the top academic medical centers in the world, is known both for its research and its clinical expertise. It has four Nobel Prize winners on its faculty - more than any other medical school in the world - and has 17 members of the National Academy of Sciences and 17 members of the Institute of Medicine. These scientists and physicians and more than 1,500 other full-time faculty members train 4,000 students and clinical residents each year, as well as oversee more than 2,000 research projects totaling more than $340 million annually. The UT Southwestern faculty has some of the nation's best doctors, including more than 200 faculty physicians who have been voted as among the best medical specialists in America. Patient care is provided at UT Southwestern University Hospitals and Clinics located in the Southwestern Medical District of Dallas, Texas. Each year UT Southwestern faculty and residents provide inpatient hospital care to nearly 87,000 patients and oversee approximately 2 million outpatient visits. Treatment of cancers, including breast cancer, prostate disease, heart disease, neurological disorders, and childhood diseases are among the many areas of expertise for which UT Southwestern is recognized.