Bomedemstat (LSD1 inhibitor) shrinks spleen and improves fibrosis markers in JAKi-refractory myelofibrosis

Bomedemstat (IMG-7289/MK-3543) is an oral, irreversible lysine-specific demethylase 1 (LSD1/KDM1A) inhibitor evaluated in an open-label Phase 1/2 study in myelofibrosis patients refractory/resistant to, inadequately controlled by, or intolerant of approved therapies (n=89; NCT03136185). Any-cause AEs occurred in 97% with thrombocytopenia (48%) and dysgeusia (36%) most common; grade 3-5 AEs occurred in 69%, and 3% had fatal AEs deemed unrelated to treatment; dosing was titrated to a platelet target (≥50 to ≤75×10^9/L), underscoring thrombocytopenia as an on-mechanism constraint. At week 24 among those with imaging data (n=35), 66% had any spleen volume reduction and 26% achieved ≥20% reduction—below the canonical SVR35 week-24 benchmark seen with frontline JAK inhibitors in JAKi-naïve MF (e.g., ruxolitinib ~42% SVR35 in COMFORT-I; fedratinib ~47% in JAKARTA), but this dataset is in a post-therapy, higher-need population and reports a lower spleen-response bar (≥20%). Exploratory signals included symptom improvement (including fatigue), marrow fibrosis improvement by ≥1 grade in 23% (8/35), and VAF reductions in 56% (of mutation-positive patients with week-24 data, n=36), suggesting potential disease-modifying activity beyond spleen control.