ZE74-2882 / Eilean Therapeutics - LARVOL DELTA

ZE74-0282 is a novel JH2 domain JAK2 inhibitor with promising pre-clinical activity in JAK2 V617F mutant diseases (ASH 2025) - "Current available JAK2 inhibitortherapies such as ruxolitinib and fedratinib target the JH1 domain and provide symptomatic relief but arelimited by non-selective JAK inhibition and disruption of WT JAK2 signaling. ZE74-282 is a first-in-class, JH2 domain specific JAK2 inhibitor with potent and selectiveactivity against mutant JAK2V617F while preserving normal JAK2-mediated function. Compared with JH1directed JAK2 inhibitors ZE74-2882 offers a superior therapeutic index in preclinical models,pharmacology suggesting twice daily dosing, and exceptional "drug properties" with ADME studiescompleted to date. These findings support its further development as a potentially disease-modifyingtherapy for JAK2 V617F mutated diseases."

Preclinical • Essential Thrombocythemia • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • ASXL1