- In Alport syndrome (AS), bardoxolone methyl targets molecular pathways that promote the resolution of inflammation, which if unchecked, leads to chronic inflammation, and ultimately, progressive loss of kidney function. Bardoxolone methyl is being studied in Reata’s pivotal, registration, phase 2/3 CARDINAL trial
- In Friedreich’s ataxia (FA), omaveloxolone targets the chronic inflammation and mitochondrial dysfunction associated with this neurologic disorder. Omaveloxolone is being studied in the pivotal, registration, MOXIe trial
- In connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), bardoxolone methyl targets the mitochondrial dysfunction and increased NF-κB activation, which are among the pathologic factors underlying CTD-PAH. Bardoxolone methyl is being studied in Reata’s phase 3 CATALYST trial
Reata’s development program has produced a robust pipeline of late-stage therapeutic candidates for the treatment of serious diseases with significant unmet needs. Reata’s lead pivotal programs include AS, FA, and CTD-PAH, which are chronic diseases characterized by ongoing inflammation and mitochondrial dysfunction.
Reata’s lead drug candidates, bardoxolone methyl and omaveloxolone, have novel mechanisms of action that target the underlying pathogenic pathways involved in chronic inflammation. Research has shown that prolonged mitochondrial dysfunction and oxidative stress, including their molecular components, proinflammatory mediators called cytokines and ROS, are major contributors to chronic inflammation.
Bardoxolone methyl and omaveloxolone activate the Keap1/Nrf2 pathway. The Keap1/Nrf2 pathway plays a key role in the resolution of inflammation by normalizing mitochondrial function, restoring redox balance, and suppressing cytokine production. Bardoxolone methyl and omaveloxolone—exhibit broad anti-inflammatory, antifibrotic, and promitochondrial activity in vitro and in preclinical disease models.
Reata is developing bardoxolone methyl in four other rare forms of CKD including: autosomal dominant polycystic kidney disease (ADPKD), IgA nephropathy (IgAN), type 1 diabetic CKD (T1D CKD), and focal segmental glomerulosclerosis (FSGS). The clinical activity observed in patients with ADPKD, IgAN, and T1D CKD supports the hypothesis that bardoxolone methyl targets the final common pathway of kidney function loss relevant to many forms of CKD.
Reata’s pipeline also includes RTA 901, which has shown favorable activity in a range of preclinical models of neurodegeneration and neuroprotection, including diabetic neuropathy and neural inflammation. Reata’s development queue also includes RTA 1701, an orally bioavailable, allosteric inhibitor of RORγt for the potential treatment of a broad range of autoimmune and inflammatory disorders.