RTA 901: A C-Terminal Heat Shock Protein 90 (Hsp90) Modulator with Neuroprotective and Neuroregeneration Potential

Overview

  • Heat shock protein 90 (Hsp90) is a molecular chaperone that plays important roles in protein folding and the heat shock response. Activation of the heat shock response results in increased expression of Hsp70, a key molecular chaperone that helps maintain normal mitochondrial function and has profound neuroprotective activity1-3
  • Reata is developing a novel class of Hsp90 modulators that bind to the C-terminus of the protein and induce Hsp70-dependent neuroprotective activity without affecting Hsp90 protein-folding activity. Our lead product candidate, RTA 901, has shown favorable activity in a range of preclinical models of neurodegeneration and neuroprotection, including diabetic neuropathy and neural inflammation
  • Results from a phase 1 clinical trial of RTA 901 demonstrated an acceptable pharmacokinetic profile without apparent safety or tolerability issues

RTA 1701: A Candidate for the Treatment of Autoimmune and Inflammatory Disorders

Overview

  • RORγt is an orphan nuclear receptor that controls T helper 17 (Th17) cell differentiation4
  • Reata has identified a series of potent and selective RORγt inhibitors that act through a novel allosteric binding mode to block Th17 cell differentiation. Our lead product candidate, RTA 1701, is orally bioavailable and demonstrates significant efficacy in animal models of rheumatoid arthritis and multiple sclerosis. RTA 1701 has the potential to be a best-in-class oral RORγt inhibitor for the treatment of chronic inflammatory and autoimmune diseases
  • A phase 1 clinical trial to evaluate the safety and pharmacokinetics of RTA 1701 and assess ex vivo suppression of IL-17A production is ongoing. Initial results are expected in the first half of 2019
References
  1. Saibil H. Chaperone machines for protein folding, unfolding and disaggregation. Nat Rev Mol Cell Biol. 2013;14(10):630-642.
  2. Craig EA. Hsp70 at the membrane: driving protein translocation. BMC Biol. 2018;16(1):11.
  3. Leu JI, Barnoud T, Zhang G, et al. Inhibition of stress-inducible HSP70 impairs mitochondrial proteostasis and function. Oncotarget. 2017;8(28):45656-45669.
  4. Martinez GJ, Nurieva RI, Yang XO, Dong C. Regulation and function of proinflammatory TH17 cells. Ann N Y Acad Sci. 2008;1143:188-211.