OPN-2853
differentiated BET bromodomain inhibitor
Target
Hit identification
Lead optimization
Preclinical
Phase 1
Phase 2
Target:
BET
Therapeutic area:
myelofibrosis
Value:
- potential best-in-class BET inhibitor
- clinically validated target
- clinical data shows 50% reduction in spleen length
- active as single agent and in combination
Safety:
- well tolerated at 80mg once daily orally
- reduced thrombocytopenia in comparison to standard-of-care
Next milestone:
recommended Phase 2 dose in
combination with ruxolitinib
OPN-2853: 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.
Clinical trials
OPN-2853 is currently being tested in patients with myelofibrosis in combination with ruxolitinib for patients who have not responded to ruxolitinib alone. This study is being conducted through a collaboration with Cancer Research UK and the University of Birmingham.
To learn more about this trial, please click below.
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