ZE74-0282 / Eilean Therap - LARVOL DELTA

A Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZE74-0282 in Healthy Volunteers. (ANZCTR) - P1 | N=40 | Not yet recruiting | Sponsor: Eilean Therapeutics AU Pty Ltd (A subsidiary of Eilean Therapeutics LLC)

First-in-human • New P1 trial • Myeloproliferative Neoplasm • Oncology

Eilean Therapeutics Advances ZE74-0282, a Highly Selective Inhibitor of Mutated JAK2 V617F, into First-in-Human Clinical Development (PRNewswire) - "An IND application has been submitted to support first-in-human clinical studies of ZE74-0282. The initial clinical study is designed as a single ascending dose trial in healthy volunteers, with objectives to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and target engagement. Enrollment in the first-in-human study is planned to begin in the first quarter of 2026. In parallel, Eilean Therapeutics is preparing for subsequent clinical studies in patients with myelofibrosis and other myeloproliferative disorders, with the intent to transition efficiently from healthy volunteer evaluation into patient-based studies focused on JAK2 V617F–driven disease."

First-in-human • IND • JAK2V617F • New trial • Myelofibrosis • Myeloproliferative Neoplasm

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

Eilean Therapeutics to Present First-in-Class, Wild-Type-Sparing JAK2-JH2/V617F Inhibitor ZE74-0282 at ASH 2025 and Initiate Clinical Studies in December 2025 (PRNewswire) - "Picomolar potency and > 500-fold selectivity for JAK2 V617F JH2 versus WT JAK2 JH2 in cellular assays; 100× selective inhibition of pSTAT5 phosphorylation and proliferation in BaF3 JAK2 V617F and SET-2 JAK2 V617F cells, with minimal effect on WT cells; Nanomolar potency in selectively reducing pSTAT5 in myeloid cells from human JAK2 V617F⁺ MPN whole-blood assays, with no effect on lymphoid cells—confirming wild-type sparing. In contrast, ruxolitinib suppressed signaling across both lineages; Selective inhibition of colony formation from JAK2 V617F/ASXL1-mutant progenitors, without affecting WT JAK2 progenitors, in murine colony-forming assays....Eilean Therapeutics plans to initiate its first-in-human clinical study of ZE74-0282 in December 2025."

JAK2V617F • New trial • Preclinical • Myeloproliferative Neoplasm