CPI-0209 is a second-generation EZH2 inhibitor that has been designed to achieve comprehensive target coverage through extended on-target residence time.
EZH2 acts as an epigenetic writer and normally places one or more methyl groups on a histone protein, leading to the suppression of gene expression. Some cancers depend on an abnormal pattern of gene expression and re-direct EZH2 to genes that become abnormally repressed. Cancer cells with these abnormal gene expression programs may be more resistant to anti-cancer therapies.
Abnormal EZH2 function has been implicated in a number of ways in specific cancers, a finding that offers broad therapeutic potential for EZH2 inhibition:
- Synergy with oncogenic drivers in prostate cancer
- Activating mutations in lymphoma
- Tumor immunity in solid tumors
- Drug resistance in solid tumors
- Synthetic lethality in genetically defined solid tumors
CPI-0209 has demonstrated more potent anti-tumor activity compared with first-generation EZH2 inhibitors in preclinical models of multiple cancer types. It does not induce its own metabolism, which has been an issue with other EZH2 inhibitors.