SirT Modulators

Elixir's founding technology is based on the identification of genes and pathways that regulate aging, and we have mined these pathways to develop products for the treatment of age-related diseases, including metabolic disease. One such target involves a gene known as Sir2 which expresses one member of a class of enzymes called sirtuins, or SIRTs. Initial enthusiasm around the sirtuins was generated based on discoveries made by an Elixir founder showing Sir2 plays a potential role in increasing lifespan. When the amount of the Sir2 enzyme was increased in a simple organism, yeast, it led to an increase in its lifespan. This finding generated significant interest in the seven human sirtuins, referred to SIRT1-SIRT7, and in drug discovery and development efforts for the treatment of age-related diseases, most notably the major metabolic diseases.

Further in vitro research suggests SIRT1 is intimately involved in the regulation of a variety of very important basic cellular functions, including cell cycle control, cell survival, mitochondrial function and intracellular metabolism. Recently, animal models have shown SIRT1 has been implicated in the control of glucose homeostasis and fat mobilization, suggesting that increasing the amount of the SIRT1 enzyme may improve metabolic function.

Conversely, blocking the amount or activity of SIRT1 has recently been shown to reverse "epigenetic silencing," a phenomenon that decreases the expression of important tumor suppressor genes. The implication of these findings is that blocking SIRT1 could be important in combating several types of cancer. These observations highlight the large potential, and explain the recent interest, in the discovery and development of compounds which could either increase or decrease the enzymes of this important class of SIRT targets.

Leveraging our knowledge of the regulation of aging and metabolism, Elixir has built a leadership position in the field of sirtuins. The Company has an extensive intellectual property position around the screening, chemical composition of matter and novel uses of SIRT modulators.

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