INCA036978

INCA036978 is an investigational, oral small molecule inhibitor developed by Incyte Corporation for the treatment of myeloproliferative neoplasms (MPNs), including myelofibrosis, polycythemia vera, and essential thrombocythemia. The drug specifically targets the oncogenic interaction between mutant calreticulin (CALR) and the thrombopoietin receptor (MPL). In MPN patients harboring CALR mutations, the mutant CALR protein acts as a ligand that constitutively activates MPL, driving pathogenic JAK-STAT signaling and uncontrolled cell proliferation. INCA036978 is designed to disrupt this binding interface, thereby inhibiting downstream signaling pathways that lead to disease progression. It is currently being evaluated in a Phase 1 clinical trial (NCT06244108) as both a monotherapy and in combination with standard disease-directed therapies.