Alnylam Forms Collaboration with University of California, San Francisco (UCSF) to Investigate Therapeutic Silencing of Key Gene Implicated in Uveal Melanoma

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has formed an exclusive collaboration with the University of California, San Francisco (UCSF) to evaluate the potential of an RNAi therapeutic targeting a heterotrimeric G protein alpha-subunit, known as G-alpha q or GNAQ, for the treatment of metastatic uveal melanoma. The collaboration is based on new data that UCSF scientists, along with collaborators, published in the journal Nature suggesting that GNAQ plays an important role in the development of uveal melanoma.

“We very much look forward to working with Alnylam’s scientific team to evaluate innovative therapies for patients with uveal melanoma”

“The emerging data on cancer genomes and the molecular basis for malignant cell transformation form a very compelling opportunity for the advancement of RNAi therapeutics targeting genes derived from somatic mutations. In this case, we are excited to be collaborating with UCSF on this program, as there is a clear need for novel therapeutics to effectively treat patients with advanced uveal melanoma,” said Jared Gollob, M.D., Senior Director, Clinical Research of Alnylam Pharmaceuticals. “The new data published in Nature greatly increases our understanding of the biology of this disease, and given our clear success in achieving systemic delivery we believe that an RNAi therapeutic targeting GNAQ in uveal melanoma that has spread to the liver may represent an ideal treatment option for this devastating disease. Uveal melanoma represents another example of an orphan indication that Alnylam intends to pursue where there is a very high unmet need and a clear opportunity for a significant therapeutic impact for patients.”

“We very much look forward to working with Alnylam’s scientific team to evaluate innovative therapies for patients with uveal melanoma,” said Boris Bastian, M.D., Professor of Dermatology and Pathology, and Leader, Cutaneous Oncology Program at UCSF.

GNAQ is involved in mediating intracellular signals which are capable of promoting cell proliferation and survival. Normally, GNAQ is only activated by its associated receptor; however, mutated forms of GNAQ confer a persistently activated state for the protein, which leads to inappropriate signaling. This Nature publication (Raamsdonk et al., Nature, advance online publication 10 December 2008; doi:10.1038/nature07586) reports on the first example of a GNAQ mutation associated with cancer in humans – specifically, uveal melanoma – and the silencing of GNAQ with a small interfering RNA, or siRNA, the molecules that mediate RNAi. The study found that:

mutated GNAQ was found in approximately 50% of patients with uveal melanoma. In these patients, the mutation always resulted in a change in the same amino acid within the protein which then resulted in uncontrolled activation of that protein;
insertion of the mutated GNAQ gene into human melanocytes, or pigment cells, transformed these cells into cancer cells that grew and formed tumors both in vitro and in a mouse model; and
siRNAs targeting GNAQ in human uveal melanoma cells demonstrated approximately 70% silencing of GNAQ, which then resulted in growth inhibition, cell death, and the inability to form tumors in vitro.

About Uveal Melanoma

Uveal Melanoma is a highly aggressive cancer of the eye arising from melanocytes of the iris, ciliary body and choroidal plexus. The disease is diagnosed in approximately 1,500 patients each year in the U.S. Despite successful treatment of the original tumor in the eye, the disease metastasizes to the liver in approximately 50% of these patients within two to five years of onset. There are currently no effective treatment options available for patients with uveal melanoma once it has metastasized to the liver, and it is uniformly fatal with a life expectancy of six to twelve months.

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. RNAi therapeutics target the cause of diseases by potently silencing specific messenger 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 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 http://www.alnylam.com.

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 company’s ability to successfully research and develop products such as products for the treatment of metastatic uveal melanoma, 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.