Reata is developing a series of Antioxidant Inflammation Modulators (called “AIMs”) with activity against a number of intractable diseases.
These unique drugs help to restore the balance between pro-oxidant and antioxidant signaling molecules within the cell by mimicking the body’s own natural regulators of inflammation. They increase the production of enzymes that maintain the antioxidant buffering system within the cell. Through this mechanism, AIMs prevent harmful inflammation and the associated oxidative stress and organ/DNA damage caused by excessive oxygen and nitrogen radicals. Also, by activating enzymes that maintain the antioxidant buffering system, they increase the body’s ability to protect against tissue damage from toxic insults, chronic health problems, and aging.
These activities occur through the control of several key transcription factors or “master switches” that simultaneously turn on groups of pro-inflammatory or anti-inflammatory genes. The AIMs have been shown to be the most potent activators of the transcription factor Nrf2, which promotes the production of important antioxidant and detoxification enzymes. The AIMs activate Nrf2 by mimicking the activity of endogenous lipid mediators that play a key role in the resolution of inflammation.
Researchers at leading institutions have defined how and where this binding occurs at the molecular level. Activation of Nrf2 and production of antioxidant enzymes inhibits important pro-inflammatory transcription factors including NF-κB and STAT3.
Reata believes that mimicking this endogenous system for controlling inflammation has two major advantages over competing approaches. First, it addresses a fundamental problem in inflammation research – the high redundancy and complexity of signaling pathways. This redundancy limits the effectiveness of agents that focus on a single molecular target. Secondly, molecules that target this endogenous system should be well tolerated with excellent safety profiles.
Click here for a more detailed description of the mechanism of action of the AIMs.
Restoration of redox balance, or “homeostasis” has implications in a broad range of diseases associated with oxidative stress, toxic injury, and aging. These include renal/cardiovascular disease, autoimmune diseases (rheumatoid arthritis, multiple sclerosis),
transplants, respiratory disease, neurodegenerative disease, and cancer. Human and animal studies conducted by leading researchers support the use of AIMs in each of these therapeutic areas.
Reata owns the intellectual property rights to multiple classes of AIMs and is developing drugs targeting a number of indications. The furthest advanced AIM compound, known as Bardoxolone methyl, is entering late-stage clinical trials for chronic kidney disease. Results from three clinical studies show that this drug is extremely well tolerated, affects the targeted biological pathways, and has produced significant and sustained improvements in renal function. Data
were presented at scientific meetings during the first half of 2009.
Additionally, Reata is developing other AIMS for the treatment of multiple sclerosis/neurodegenerative disease and COPD. |
