A Phase 2 Study of the LSD1 Inhibitor Img-7289 (bomedemstat) for the Treatment of Advanced Myelofibrosis (original) (raw)

Blood, 2021

Abstract

There is an unmet need for novel therapies with distinct modes of action to offer clinical benefit for patients with myelofibrosis (MF) who become resistant or intolerant to JAK inhibitors. Lysine-specific demethylase-1 (LSD1) is a histone demethylase critical for self-renewal potential of malignant myeloid cells for hematopoietic differentiation, e.g., LSD1 licenses maturation of megakaryocytes, one cell type critical to the pathogenesis of MF. Bomedemstat is an orally active LSD1 inhibitor that in mouse models of MPNs reduced peripheral cell counts, splenomegaly, inflammatory cytokines, marrow fibrosis, mutant cell burden and overall survival (Jutzi et al. 2018). IMG-7289-CTP-102 is a global, open-label Phase 1/2 study evaluating bomedemstat dosed once daily in MF patients (NCT03136185). Data from this ongoing study are presented. Key eligibility criteria include IPSS int.-1 or -2 or high-risk patients refractory or resistant to, inadequately controlled by or intolerant of availab...

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