OPN-2853: a potential Best-In-Class BET inhibitor

Bromo- and extra-terminal domain (BET) proteins regulate transcription by reading acetylation marks on histones, playing an important role in homeostasis and cell survival.

In myelofibrosis (MF), the standard of care is janus kinase (JAK) inhibition, which reduces cytokine production and lessens symptoms such as spleen volume. However, treatment is not curative and many patients become refractory to JAKi. BET inhibition controls inflammation triggered by epigenetic changes in the BRD4 /NF-kB dependent regulatory network and normalizes megakaryocytic differentiation.

Combination therapy:

OPN-2853 selectively inhibits the BET protein recognition of acetylated histones and down-regulates oncogenic gene expression, with an optimized oral PK and safety profile that makes it uniquely combinable with other targeted drugs to accomplish full pathway inhibition.

The combination of OPN-2853 with JAK inhibitors such as ruxolitinib may synergize to reduce inflammation, splenomegaly and bone marrow fibrosis, and is currently being tested in a Phase 2 clinical study.