Prelude Therapeutics Presents Data at 2025 ASH Annual Meeting from its Myeloproliferative Neoplasm Programs
Key claim: PRT12396, a JAK2V617F-selective JH2 pseudokinase domain inhibitor, shows robust preclinical anti-MPN activity superior to ruxolitinib while sparing wild-type JAK2-mediated cytokine signaling, with IND filing and Phase 1 initiation anticipated in Q1 2026.
Abstract
PRT12396, a JAK2V617F mutant-selective JH2 inhibitor, selectively inhibits JAK2V617F activity while preserving wild-type JAK2-mediated cytokine signaling and demonstrated robust preclinical activity in multiple MPN models, superior to ruxolitinib. GLP toxicology studies have been completed and IND filing with Phase 1 initiation is anticipated in Q1 2026.
Why this matters
Across JAK2V617F-driven MPN subtypes (PV ~95%, ET ~50–60%, and a major fraction of PMF), current JAK inhibitors are limited by concurrent suppression of wild-type JAK2 cytokine signaling, which drives cytopenias and constrains disease modification. PRT12396’s preclinical demonstration of mutant-selective JAK2V617F inhibition with superiority to ruxolitinib establishes a mechanistically distinct option that could differentially benefit each JAK2-mutated subtype according to its baseline cytopenia/burden profile, and joins the broader next-generation JAK2-targeted pipeline (AJ1-11095 type II JAK2i) shaping subtype-specific therapeutic trajectories.