Undisclosed JAK2V617F mutant specific allosteric inhibitor / Atavistik Bio - LARVOL DELTA

Discovery of JAK2V617F mutant specific allosteric inhibitors for the treatment of myeloproliferative neoplasms (ASH 2025) - "The V617F mutation in Janus Kinase 2 (JAK2V617F) is a recurrent driver of myeloproliferative neoplasms(MPNs), including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET).Current therapies targeting the JAK-STAT pathway such as pan-JAK inhibitors (JAKi) like Ruxolitinib havedemonstrated clinical benefit but are limited by a lack of disease-modifying activity. Additionalstudies in preclinical models of JAK2V617F driven splenomegaly are currently underway.In summary, we have discovered novel, potent, and selective allosteric inhibitors of JAK2V617F thateffectively suppress pathogenic, cytokine-independent JAK2V617F driven signaling and cell proliferationwhile sparing normal cytokine-dependent signaling. These findings support the development of highlymutant selective inhibitors for the treatment of JAK2V617F driven MPNs."

Essential Thrombocythemia • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • STAT5 • TYK2

Atavistik Bio to Present Discovery of JAK2 V617F Mutant-Selective Allosteric Inhibitors for the Treatment of Myeloproliferative Neoplasms (MPNs) at ASH 2025 (GlobeNewswire) - "In preclinical models, these compounds show potent inhibition of JAK2 V617F-dependent signaling and proliferation in multiple human hematopoietic cancer cell lines harboring the mutations while sparing wild-type JAK2 cells....In a mouse model bearing JAK2 V617F-expressing SET2 tumors, Atavistik JAK2 V617F selective inhibitors demonstrated strong target engagement, evidenced by reduced phosho-STAT5 levels."

JAK2V617F • Preclinical • Myeloproliferative Neoplasm