LY5830966

LY5830966 (also known as AJ1-11095) is an orally bioavailable, first-in-class, small molecule type II Janus kinase 2 (JAK2) inhibitor. Unlike approved type I JAK2 inhibitors that bind to the active conformation of JAK2, LY5830966 selectively binds to the inactive (type II) conformation of the kinase. This mechanism of action prevents both JAK2 homodimerization and heterodimerization of JAK2 with JAK1 and TYK2, thereby overcoming clonal persistence and drug resistance associated with type I inhibitors. Originally developed by Ajax Therapeutics in collaboration with Schrödinger, the asset was acquired by Eli Lilly and Company in April 2026. It is currently being evaluated in Phase 1 clinical trials for the treatment of myeloproliferative neoplasms, including primary or secondary myelofibrosis and high-risk relapsed/refractory polycythemia vera.