Rigel’s investigational candidates are oral, potent and selective inhibitors of receptor-interacting serine/threonine-protein kinase 1 (RIPK1).

RIPK1 is a critical signaling protein implicated in a broad range of key inflammatory cellular processes including necroptosis, a type of regulated cell death, and cytokine production. In necroptosis, cells rupture leading to the dispersion of cell contents, which can trigger an immune response and enhance inflammation. RIPK1 inhibition has therapeutic potential in treating autoimmune, inflammatory, and neurodegenerative disorders.

Rigel’s RIPK1 inhibitor program includes R552, a systemic molecule being developed for the treatment of autoimmune and inflammatory disorders, and brain penetrating RIPK1 inhibitors for central nervous system (CNS) diseases. In preclinical studies, R552 demonstrated prevention of joint and skin inflammation in a RIPK1-mediated murine model of inflammation and tissue damage.

Development of R552:

  • Phase 1 studies complete
  • The initial Phase 2a study in approximately 100 patients with moderately to severely active rheumatoid arthritis (RA) is anticipated to begin in the first half of 2023 with partner Eli Lilly. The Phase 2a study analysis is expected by the end of 2024

Development CNS-penetrating RIPK1 inhibitors:

  • Currently in preclinical studies