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Reata's Synthetic Triterpenoids Profiled in Nature Reviews Cancer

gulate activation of NF-kB by binding to IKKB, the kinase that inhibits NF-kB activation. The triterpenoids block the activation of STAT3 and STAT5 in cancer cells by upregulating negative regulators of the STATs. These transcription factors are the target of major drug development programs at multiple companies with applications in treating both inflammation and cancer.

-- A description of the anti-inflammatory and anti-carcinogenic activity of the compounds. Reata's triterpenoids suppress production of pro-inflammatory cytokines and reduce mortality in animal models of LPS-induced inflammation. Synthetic triterpenoids are highly effective in preventing the development of both lung cancer and liver cancer in animals exposed to known carcinogens.

-- Multi-functional anti-cancer activity of these drugs, which includes driving immature cancerous cells to differentiate; inhibiting the growth of cancer cells and causing them to undergo programmed cell death (called apoptosis). This activity has been seen in multiple animal models, and has recently been confirmed in a Phase 1 study of RTA 402 in cancer patients being conducted at the M.D. Anderson Cancer Center and the Dana-Farber Cancer Institute.

-- A comparison of the mechanism of the Synthetic Triterpenoids with that of "targeted therapies" currently in vogue in the cancer field. Dr. Sporn argues that the genetic complexity of cancer requires the use of agents with a multi-factorial mode of action, rather than those with high affinity for a single, specific molecular receptor. While multi-factorial mechanisms are often thought to be associated with high drug toxicity, Dr. Sporn notes that these agents are derived from natural products that have been safely used for centuries with no appreciable toxicities. Recent clinical studies have shown that these agents are minimally toxic in humans.

About Reata

Reata Pharmaceuticals, Inc. is a biopharmaceutical company focused on selecting and
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