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[DewDiligence]

AMD discussion from ALNY’s 10K report

http://access.edgar-online.com/emailAlert.asp?SessionID=Ava7ykyXi0BdQrA&FilingID=3571953&Typ...
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Current Treatments

Until recently there were only two available treatments, of limited effectiveness, for wet AMD: the drug Visudyne, sold by Novartis AG, and laser treatment. Visudyne is used in a two-step process known as photodynamic therapy whose goal is to seal newly formed blood vessels behind the retina so that they neither grow nor leak. However, Visudyne is only approved for the treatment of certain subtypes of wet AMD, and its beneficial effects are frequently modest and of limited duration. The only alternative to photodynamic therapy was, until recently, treatment with a laser to burn out newly formed blood vessels. Unfortunately, this treatment can also cause irreversible damage to the retina, resulting in significant blind spots, and its beneficial effects appear to be of limited duration.

In December 2004, the United States Food and Drug Administration, or FDA, approved a new drug known as Macugen for the treatment of all types of wet AMD. Macugen belongs to a class of compounds known as aptamers and blocks the activity of a protein known as vascular endothelial growth factor, or VEGF. There is evidence that VEGF promotes both the growth and the leakage of new blood vessels behind the retina in AMD. Macugen was developed by Eyetech Pharmaceuticals, Inc. Several other companies are developing drugs for the treatment of wet AMD that target VEGF or its activity. The most advanced of these drug candidates is Lucentis, an antibody fragment being developed by Genentech, Inc. that binds specifically to VEGF. Regeneron, Inc. is developing a product called VEGF Trap, designed to block the activity and effects of VEGF, that is in the early stages of clinical testing for AMD. Two other companies are in the early stages of developing siRNA products to block VEGF activity. One of these products, being developed by Acuity Pharmaceuticals, Inc., is intended to limit production of VEGF by suppressing the activity of the VEGF gene. The other, being developed by Sirna Therapeutics, Inc., is intended to limit production of a protein known as VEGF-receptor, which is the protein on cell surfaces that VEGF must bind to in order to exert its effects. Acuity and Sirna both initiated Phase I human clinical trials of their siRNA products in the latter half of 2004.

Alnylam Program

We are developing an RNAi therapeutic, which we refer to as VEGF Production Inhibitor, for the treatment of wet AMD. We believe that an RNAi therapeutic that suppresses VEGF gene activity, thereby cutting off VEGF production, could have significant advantages over drugs that bind to VEGF once it has been produced or that limit production of the VEGF-receptor. We have identified siRNAs that suppress the activity of the VEGF gene potently and specifically in cultured cells. We believe that the siRNAs we have identified are significantly more potent and effective than VEGF-directed siRNAs reported by others, and that we can apply the current capabilities of our product engine to develop them into competitive drug candidates. We are currently evaluating these siRNAs in animal models relevant to wet AMD and expect to begin a clinical trial for a wet AMD product candidate during the second half of 2005.

Any siRNA we develop for wet AMD will be a Direct RNAi drug administered by direct injection into the eye, the method of administration for Macugen and Lucentis. We have filed patent applications relating to the use of siRNAs to suppress VEGF production for therapeutic purposes, and in August 2004, we obtained an exclusive license from Hybridon, Inc., under a number of issued patents covering the treatment of ocular diseases with siRNAs targeting VEGF.
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