Reata’s mission is to develop novel therapeutics for patients with serious or life-threatening diseases by targeting molecular pathways involved in regulating cellular metabolism and inflammation. Our lead product candidates, bardoxolone methyl and omaveloxolone, are members of a class of small molecules called antioxidant inflammation modulators, or AIMs. Bardoxolone methyl is in Phase 3 clinical development for the treatment of pulmonary arterial hypertension associated with connective tissue disease, or CTD-PAH. We recently enrolled the first patient in our Phase 3 CTD-PAH trial, CATALYST, which is examining the safety, tolerability, and efficacy of bardoxolone methyl when added to standard-of-care vasodilator therapy. CATALYST is enrolling between 130 and 200 patients at 100 sites in the United States, Canada, Australia, Mexico, Europe, Israel, Japan, and South America. Bardoxolone methyl is also in Phase 2 clinical development for four types of pulmonary hypertension, or PH, due to interstitial lung disease, or PH-ILD. We are also currently designing a Phase 2/3 trial for bardoxolone methyl in Alport Syndrome and plan to initiate the Phase 2 portion of the integrated Phase 2/3 in the first half of 2017. Omaveloxolone is in Phase 2 clinical development for the treatment of multiple diseases, including Friedreich’s ataxia, or FA, and mitochondrial myopathies, or MM, sometimes referred to as mitochondrial disease with myopathy. Beyond our lead product candidates, we have several promising preclinical development programs employing both AIMs and other small molecules with different mechanisms of action. We believe that our product candidates and preclinical programs have the potential to improve clinical outcomes in numerous underserved patient populations.
AIMs activate Nrf2, a transcription factor that promotes normal mitochondrial function, increases production of antioxidant and detoxification enzymes, reduces oxidative stress, and reduces pro-inflammatory signaling during the resolution of a normal, healthy inflammatory response. Since mitochondrial dysfunction, oxidative stress, and inflammation are features of many diseases, AIMs have many potential clinical applications and have been the subject of more than 350 peer-reviewed scientific papers. In addition to the AIMs programs, we have technologies in preclinical development targeting the treatment of diseases through a variety of mechanisms. Our most advanced preclinical compound, RTA 901, targets pathways involved in the cellular response to misfolded proteins and mitochondrial protein import. It and related analogs have shown promising effects in animal models of neural disease.
- Bardoxolone methyl (formerly designated as RTA 402) is currently in a Phase 3 (CATALYST) study for the treatment of pulmonary arterial hypertension associated with connective tissue disease and a Phase 2 (LARIAT) study for the treatment of pulmonary hypertension due to interstitial lung disease. It is also being studied in a Phase 2 trial (TSUBAKI) in Japan in patients with chronic kidney disease.
- Planned initiation for bardoxolone methyl in a Phase 2/3 study for the treatment of Alport syndrome
- Phase 2 studies of omaveloxolone have been initiated in two genetic disorders involving mitochondrial dysfunction: Friedreich’s ataxia (enrollment underway in MOXIe) and mitochondrial myopathies (enrollment underway in MOTOR).
- Omaveloxolone is in a Phase 1b/2 study in melanoma patients to test its ability to augment checkpoint inhibitors such as ipilimumab and nivolumab (REVEAL).
- Omaveloxolone has also been formulated into a sterile ophthalmic suspension and has been tested in a Phase 2 study for prevention of corneal endothelial cell loss due to cataract surgery (GUARD).
Additional information on the pharmacology of the AIMs can be found here.
Beyond our platform technologies and in-licensed compounds, we are constantly working on novel science and have active internal discovery and preclinical programs in a number of significant disease areas. In addition to internal discovery, we continue to seek additional opportunities to in-license and collaboratively develop novel technologies from premier academic institutions. This operating model of combined internal discovery, in-licensing, and collaborative development guided the founding of Reata, and we continue this strategy today to maintain a pipeline of promising development programs.