Alnylam Pharmaceuticals (NASDAQ: ALNY) is a leader in the field of RNA interference, or RNAi. RNAi, a breakthrough discovery in biology, 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 an entirely new way to treat a wide range of human diseases. Alnylam is working to harness the RNAi mechanism to silence genes whose activity is implicated in the cause or pathway of human disease. Working both independently and with top-tier collaborators, Alnylam is building a deep pipeline of RNAi therapeutics to treat a wide range of diseases.

Alnylam maintains a leadership position in this promising field, with a goal of realizing RNAi’s full potential for therapeutic applications. The unique mechanism of action in RNAi enables the targeting of previously ‘non-druggable’ genes. The company’s expertise in designing and optimizing RNAi molecules, together with its leading position in critical intellectual property relating to RNAi, has enabled Alnylam to form major alliances with world-class companies including Merck, Medtronic, Novartis and Biogen Idec. In these alliances and independently, Alnylam is applying its expertise in RNAi to address multiple therapeutic areas. The company’s product platform enables rapid generation and optimization of potent small interfering RNAs (siRNAs) – the molecules that mediate RNA interference – for virtually any disease target. Alnylam was founded by some of the scientific pioneers in the field of RNAi and has assembled a management team with significant product development experience. With strong financial resources and the support of its top-tier academic and industry collaborators, Alnylam has made excellent progress in building a pipeline of RNAi therapeutics.

Development Programs

Respiratory Syncytial Virus (RSV)
Alnylam's ALN-RSV01 therapeutic development program targets RSV for the treatment of RSV infection. Using our Direct RNAi approach, we will deliver the drug directly to the lungs in order to specifically silence a key viral gene in infected lung cells; hence neutralizing the virus, and preventing viral spread and further infection. RSV infection poses a great risk to young children and other immune deficient populations (e.g. elderly, bone marrow transplant); specifically, infants born prematurely and children with lung or congenital heart disease.

Alnylam conducted two Phase I trials with ALN-RSV01 to evaluate the safety, tolerability, and pharmacokinetics of ALN-RSV01 in healthy adult volunteers. Both trials were double-blind, placebo-controlled, and randomized. In total, 101 subjects were enrolled in the trials and 65 were exposed to ALN-RSV01. The subjects received a single or multiple daily doses of ALN-RSV01 or saline placebo in a nasal spray. Results show that ALN-RSV01 was safe when administered in relevant doses intranasally to human volunteers, with an adverse event profile comparable to placebo. All reported adverse events for both ALN-RSV01 and placebo subjects were mild, with no reported serious adverse events. Further, there was no evidence of laboratory or electrocardiographic abnormalities in subjects exposed to drug. Finally, as expected, there was no significant systemic exposure to ALN-RSV01 administered intranasally.

Pandemic Flu
The goal of Alnylam's influenza program is to develop Direct RNAi therapeutics effective against all flu strains including potentially highly virulent strains of flu, such as H5N1. By targeting key flu genes required for viral replication, Alnylam and its collaborator, Novartis, aim to demonstrate potent anti-viral activity for the prevention and treatment of highly pathogenic flu strains.

This program has also received initial funding support from the Department of Defense's DARPA arm. The pandemic flu effort represents Alnylam's second development program and the company expects to file an IND for pandemic flu as early as the end of 2006.

Partnerships

Merck
Alnylam and Merck are in a collaboration to develop RNAi therapeutics across a potentially broad spectrum of disease areas. Originally forged in 2003, the companies amended the terms of the collaboration in 2006 to provide Merck with a more active role in the development of RNAi therapeutic products, and Alnylam with an opportunity to receive accelerated R&D funding and the potential for significant milestones and royalty payments on commercialized products resulting from the collaborations.

The collaboration is focused on nine therapeutic targets to be nominated by Merck. Under the terms of the agreement, Alnylam may select three of the nine programs as joint development programs, which Merck will co-fund and participate in from the outset, thereby providing Alnylam with accelerated R&D funding for its efforts. In the U.S., Alnylam will have the right to co-promote RNAi therapeutic products developed in these three programs. Merck will assume primary responsibility for the remaining six programs and Alnylam is eligible to receive milestone payments and royalties on RNAi therapeutic products developed and commercialized by Merck in these programs.

Medtronic
In February 2005, Alnylam initiated a collaboration with Medtronic, the world's leading medical technology company. The collaboration will pursue the development of novel drug-device combinations incorporating RNAi therapeutics to treat neurodegenerative disorders such as Parkinson's, Huntington's and Alzheimer's. Initial work will focus on delivering RNA therapeutics to specific locations within the brain via novel infusion systems. Under the terms of the agreement, Alnylam will be responsible for discovery and early clinical development of the RNAi therapeutic products and Medtronic will be responsible for late-stage development and commercialization of the drug-device product.

Novartis
In September 2005, Alnylam and Novartis Institute for BioMedical Research (NIBR), the research institute of Novartis AG, formed a landmark alliance focused on the discovery of innovative therapeutics based on RNAi. The alliance will discover, develop and commercialize RNAi therapeutics across multiple therapeutic areas. The partnership, valued at >$700M, brings together the leader in RNAi with one of the largest and most successful innovation-based pharmaceutical company.

In February 2006, Alnylam and Novartis formed a second collaboration to jointly advance RNAi therapeutics for pandemic flu.

Biogen Idec
In September 2006, Alnylam and Biogen Idec announced a collaboration to develop RNAi therapeutics for the potential treatment of progressive multifocal leukoencephalopathy (PML). PML is caused by infection of the central nervous system with a virus called "JC virus" and can occur in certain immune-suppressed patients, including those receiving immunomodulatory therapies. Alnylam and Biogen Idec will initially conduct investigative research into the potential of using RNAi technology to develop therapeutics to treat PML. Under terms of the collaboration, Biogen Idec will fund all research and development activities.