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New Anti-Inflammation Modulator Improves Kidney/Diabetes Functions;
for CNS disease too
  View ADA Presentation: Renal Effects
View ADA presentation: Glycemic Control Effects
Phase 2a study in type 2 diabetics with chronic kidney disease (CKD)
"- Patients experienced significant improvements in eGFRand serum creatinine.
- Improvements also seen in creatinine clearance, cystatin C, BUN, uric acid, and phosphorus.
- 82%of patients with elevated baseline A1c experienced a decline.
- Euglycemic clamp results suggest an improvement in glucose metabolism.
- CV markers (CECs, AII and adiponectin) improved as well.
- BARD was well tolerated
8 Adverse Events (AEs) attributed to BARD
·4/60 (4.6%) patients experienced AEs assessed as possibly or probably related: mild muscle spasms (1), moderate decreased appetite (1), severe increased ALT (1), severe increased AST (1), severe increased ALP (1), and mild hypoglycemia (asymptomatic) (3)"
-- A 12-month Phase 2b study is underway
Reata's technological focus is on the development of small molecules to treat intractable diseases such as chronic kidney disease, COPD, neurodegenerative diseases, and cancer. Our pipeline is based around two important platform technologies:
Reata is the world leader in developing Antioxidant Inflammation Modulators (AIMs). AIMs control the balance of pro-and anti-inflammatory signaling molecules within the cell by mimicking the body's own natural regulators of inflammation. Like these natural regulators, AIMs bind to proteins responsible for sensing the redox balance, turning off master genes (called "transcription factors") that promote inflammation and turning on counter-balancing transcription factors that resolve inflammation. Through this mechanism, they turn up production of antioxidant and cytoprotective enzymes through the induction of Nrf2, while turning down the production of important pro-inflammatory mediators (known as "cytokines") such as IL-1, IL-6, and TNFα. In this way, AIMs effectively quench the inflammatory drive within inflamed cells. Reata owns the intellectual property rights to multiple classes of AIMs and is collaborating with many leading laboratories on this important emerging area of biology.
Reata is also a leader in the emerging field of protein misfolding. Reata Founding Scientist Dr. Philip J. Thomas of the University of Texas Southwestern Medical Center at Dallas was a pioneer in establishing the link between protein folding and disease. In recent years, protein folding has become an important emerging area of science and, as predicted, it has become widely accepted that defects in protein folding underlie a large number of intractable diseases including cancer, amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease), Alzheimer's disease, Parkinson's disease, and cystic fibrosis. Reata is conducting an active discovery program to identify small molecule chaperones that correct misfolded proteins using a best-in-class assay invented in Dr. Thomas' laboratory.
Reata Pharmaceuticals, Inc. today announced that results of a Phase II clinical trial of bardoxolone, its lead antioxidant inflammation modulator (AIM), ...
Antioxidant Inflammation Modulators
Reata is developing a series of Antioxidant Inflammation Modulators (called "AIMs") with activity against a number of intractable diseases.
How AIMs Work
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.
Applications for 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's AIM Portfolio
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.
AIMs for CNS Diseases
Reata is developing a series of orally available Antioxidant Inflammation Modulators (AIMs) that have been shown to cross the blood-brain barrier and achieve high concentrations in the central nervous system tissue following oral dosing. Like Reata's other AIMs, these drugs promote the resolution of inflammation by restoring redox homeostasis in inflamed tissues. They are potent inducers of the transcription factor Nrf2, which controls production of over 250 antioxidant and detoxification enzymes in the cell. Activation of Nrf2 and production of antioxidant enzymes inhibits important pro-inflammatory transcription factors including NF-κB and STAT3. These biological pathways are implicated in a wide variety of CNS diseases, including multiple sclerosis and several neurodegenerative diseases.
Multiple Sclerosis Program Several AIMs have shown outstanding activity in a number of validated animal models of multiple sclerosis. Based on the activity seen in these models, Reata plans to advance an AIM to clinical development for the treatment of multiple sclerosis.
Neurodegenerative Disease Program The mechanism of action of the AIMs is now widely recognized as an attractive therapeutic strategy for treating a number of major neurodegenerative diseases. Preclinical studies have shown that AIMs have significant activity in animal models of Alzheimer's, Parkinson's, Huntington's, and Lou Gehrig's (ALS) diseases. One recently published study, by researchers at a leading academic institution, demonstrated neuroprotective activity of an AIM in a genetic model of Alzheimer's disease. Based on these encouraging results, AIMs are undergoing evaluation as potential clinical candidates to treat neurodegenerative diseases.
Bardoxolone methyl - Oral, Once Daily AIM for Renal/Cardiovascular/Metabolic Diseases.
Bardoxolone methyl, previously known as RTA 402, is the lead molecule emerging from Reata's platform of Antioxidant Inflammation Modulators (AIMs). The AIMs are the most potent known inducers of Nrf2, an important emerging biological target that controls the production of many of the body's antioxidant and detoxification enzymes. There is a strong biological rationale for the use of agents targeting Nrf2 to treat renal and cardiovascular disease. Chronic oxidative stress-mediated inflammation is known to play an important role in the degeneration of kidney function. Based on data from three clinical studies demonstrating improvements in patients' kidney function, bardoxolone has been advanced into late stage clinical development.
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