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Alnylam Presents Pre-clinical Data from TTR Amyloidosis Development Program

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov 20, 2008 - Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it presented new pre-clinical data from its TTR amyloidosis development program at Cambridge Healthtech Institute's Drug Formulation conference held in Philadelphia, November 19-20, 2008. These data demonstrate the potential therapeutic benefit of an RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR amyloidosis, including familial amyloidotic polyneuropathy (FAP).

“Based on Alnylam's success in achieving systemic delivery of RNAi therapeutics, we are excited to be advancing an RNAi therapeutic targeting the TTR gene for the treatment of TTR amyloidosis,” said Dinah Sah, Ph.D., Vice President, Research, CNS, and Oncology. “We are very encouraged by these promising pre-clinical data and look forward to next steps with this program, which is one of our investigational new drug (IND) candidates for 2009. TTR amyloidosis is an example of a larger number of orphan-like indications that Alnylam intends to advance to the market where there is a very significant unmet medical need, the potential for early biomarker data in clinical studies that enables rapid proof-of-concept, and a clear opportunity for a large therapeutic impact for patients.”

“I am excited to be working with Alnylam on this novel program that represents an opportunity to make a profound difference in the lives of patients afflicted with this tragic disease,” said Maria Joao Saraiva, Ph.D., Professor of Biochemistry, Molecular Neurobiology Group, Institute for Molecular and Cellular Biology in Portugal. “TTR amyloidosis, which has severe manifestations in FAP, is an orphan disease estimated to affect approximately 10,000 people worldwide. The debilitating disease is associated with significant morbidity, such as intractable peripheral sensory neuropathy and disabling dysfunction of the autonomic nervous system, including severe gastrointestinal symptoms. Based on this encouraging pre-clinical data with ALN-TTR, I am excited about the advancement of this promising new RNAi therapeutic towards clinical trials.”

The new data demonstrated that highly potent RNAi therapeutics targeting TTR dramatically reduced the levels of target messenger RNA (mRNA) in the liver and TTR protein in circulation. Using Alnylam's proprietary lipid nanoparticle formulation, studies were performed in a transgenic mouse model where human TTR (hTTR) with a certain mutation known as V30M is over-expressed. Studies were also performed in non-human primates using lipid nanoparticle formulations from Tekmira Pharmaceuticals Corp. Specifically, data from these studies showed that administration of ALN-TTR resulted in:


  • dose-dependent silencing of TTR in vitro and absence of any immune stimulatory effects;
  • reduced TTR plasma levels and liver TTR mRNA by greater than 90% in the V30M-hTTR transgenic mouse model; and
  • reduced liver TTR mRNA levels by approximately 80% in non-human primates.

For most patients with TTR amyloidosis, liver transplantation is the only treatment option. These data suggest that treatment of TTR amyloidosis with an RNAi therapeutic may represent a promising alternative medical strategy, including the ability to simultaneously reduce the expression of mutant as well as wild-type TTR.

About TTR Amyloidosis

TTR amyloidosis 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, TTR amyloidosis 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 cardiac amyloidosis). TTR amyloidosis patients with FAP have a mean life expectancy of nine to eleven 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 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. 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, and Kyowa Hakko. 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 LLC, 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

Alnylam Forward-Looking Statement

Various statements in this release concerning Alnylam's future expectations, plans and prospects, 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 the results of the Company's on-going research and development, including pre-clinical and clinical testing of ALN-TTR, as well as those risks more fully discussed in the “Risk Factors” 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 Alnylam'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.



Contact: Alnylam Pharmaceuticals, Inc.
Cynthia Clayton (Investors), 617-551-8207
Yates Public Relations
Kathryn Morris (Media), 845-635-9828



Posted: November 2008