INCA033989 + Jakafi

INCA033989 + Jakafi is an investigational combination therapy consisting of INCA033989, a first-in-class, fully human, Fc-silenced IgG1 monoclonal antibody targeting mutant calreticulin (mutCALR), and Jakafi (ruxolitinib), an FDA-approved small molecule inhibitor of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2). Developed by Incyte, this combination is being evaluated for the treatment of patients with calreticulin-mutated myeloproliferative neoplasms, specifically myelofibrosis (MF). INCA033989 selectively binds to the mutant CALR protein in complex with the thrombopoietin receptor (TPO-R), leading to internalization and lysosomal degradation of the complex, which abrogates oncogenic JAK-STAT signaling and selectively eliminates CALR-mutant cells. Jakafi provides complementary symptom control and spleen volume reduction by directly inhibiting JAK1 and JAK2. In Phase 1 clinical trials, the combination has demonstrated a manageable safety profile and encouraging clinical activity, including spleen volume reductions, symptom improvements, and anemia responses in patients with myelofibrosis.

Other names

INCA-033989 + JakafiINCA-033989 + ruxolitinibINCA033989 + JakafiINCA033989 + ruxolitinibINCA033989 and JakafiINCA-033989 and JakafiINCA 033989 and JakafiINCA033989 and ruxolitinibINCA-033989 and ruxolitinibINCA 033989 and ruxolitinibruxolitinib + INCA-033989ruxolitinib + INCA033989