Oral IRAK1/4 Inhibitor for the Treatment of Autoimmune and Inflammatory Diseases:

  • The investigational candidate, R835, is an orally available, potent and selective inhibitor of interleukin receptor associated kinase (IRAK)1 and IRAK4 that blocks inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor family (IL-1R) signaling.
  • TLRs and IL-1Rs play a critical role in the innate immune response. Dysregulation of the TLR and IL-1R pathways may be associated with a variety of inflammatory conditions including psoriasis, rheumatoid arthritis, lupus and gout (among others).
  • The selective inhibition of IRAK1/4 kinases, resulting in the suppression of TLR/IL-1R-dependent signaling and associated cytokine production, may provide an attractive approach to treat a broad range of autoimmune and inflammatory diseases.
  • R835 blocks both IL-23 production in vivo and TH17 cell differentiation in vitro, providing a strong rationale for its use in the treatment of IL23/IL17-mediated diseases, such as psoriasis.
  • Rigel initiated a Phase 1 study to assess the safety, tolerability, and pharmacokinetics of R835 in healthy subjects during the second quarter of 2018.