h9H11

h9H11 is a humanized monoclonal antibody specifically engineered to target the neopeptide C-terminus of mutant calreticulin (CALR), which is a primary driver of myeloproliferative neoplasms (MPNs) such as myelofibrosis and essential thrombocythemia. In MPNs, frameshift mutations in the CALR gene (most commonly Type 1 del52 and Type 2 ins5) result in a novel C-terminal sequence that binds to and constitutively activates the thrombopoietin receptor (MPL/TpoR). h9H11 binds to specific epitopes within this mutant protein to block the interaction with MPL, thereby inhibiting downstream oncogenic JAK/STAT signaling, including STAT5 and ERK phosphorylation. Preclinical data presented at EHA 2026 indicates that h9H11, particularly when combined with other antibodies targeting distinct CALR epitopes (such as h4D7), can effectively eradicate mutant megakaryocyte progenitors and overcome resistance to JAK2 inhibitors like ruxolitinib.