Alnylam Presents New Pre-Clinical Data on ALN-TTR, an RNAi Therapeutic for the Treatment of Transthyretin-Mediated Amyloidosis

New Data Demonstrate Durable In Vivo Efficacy for ALN-TTR

CAMBRIDGE, MA, USA | November 2, 2009 | Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it presented new pre-clinical research findings from its transthyretin (TTR)-mediated amyloidosis (ATTR) program at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (“The Liver Meeting”). Alnylam is developing ALN-TTR, a systemically delivered RNAi therapeutic targeting the TTR gene for the treatment of ATTR, including familial amyloidotic cardiomyopathy (FAC) and familial amyloidotic polyneuropathy (FAP). There are more than 100 mutations that have been identified in the TTR gene. ALN-TTR targets a region of the gene common to wild-type and all known mutant forms of TTR, and therefore, has potential as a therapeutic for all patients with FAC and FAP.

“We are very encouraged by these significant and important pre-clinical findings, which continue to validate the potential benefit of an RNAi therapeutic targeting TTR for the treatment of ATTR,” said Dinah Sah, Ph.D., Vice President, Research, CNS and Oncology at Alnylam. “Our new in vivo studies represent a significant step forward as they demonstrate the ability of ALN-TTR to silence the TTR gene for a period of weeks after a single dose administration. These data provide continued validation of our RNAi therapeutics strategy, and we are looking forward to advancing this program towards the clinic.”

The new pre-clinical research findings presented at the meeting demonstrated dose-dependent ALN-TTR reduction of liver TTR messenger (mRNA) and serum TTR protein levels by greater than 80% in transgenic mice and non-human primates, with gene silencing effects found to be durable for more than three weeks following a single dose administration.

“I am quite excited by these new data, which strongly support the advancement of this program towards patients who have extremely limited therapeutic options,” said Maria Joao Saraiva, Ph.D., Professor of Biochemistry, Molecular Neurobiology Group, Institute for Molecular and Cellular Biology in Portugal. “ATTR, which presents severe manifestations in both FAP and FAC, is estimated to affect approximately 50,000 people worldwide and is associated with significant morbidity, including intractable peripheral sensory neuropathy, disabling dysfunction of the autonomic nervous system that leads to severe intestinal dysfunction, and in many cases severe cardiomyopathy.”

Alnylam expects to file regulatory applications for ALN-TTR by the end of 2009 with a goal of initiating a Phase I clinical trial in early 2010. ALN-TTR is being advanced using stable nucleic acid-lipid particles (SNALP) delivery technology in collaboration with Tekmira Pharmaceuticals Corporation.

About TTR-mediated Amyloidosis

TTR-mediated amyloidosis (ATTR) is a hereditary, systemic disease caused by a mutation in the transthyretin (TTR) gene. TTR protein is produced primarily in the liver and is normally a carrier for thyroid hormones and retinol binding proteins. The mutation causes abnormal amyloid proteins to accumulate in and damage body organs and tissue such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and cardiomyopathy. In its severest form, ATTR represents a tremendous unmet medical need with significant morbidity and mortality as an orphan disease; FAP (familial amyloidotic polyneuropathy) affects approximately 10,000 people worldwide with additional patients affected by FAC (familial amyloidotic cardiomyopathy). ATTR patients with FAP have a mean life expectancy of five to fifteen years from symptom onset and the only treatment option is liver transplantation; as a result there is a significant need for novel therapeutics to treat patients who have a mutation in the TTR gene.

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. 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, 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, Inc.

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