Tulmimetostat (CPI-0209) is an investigational next-generation dual inhibitor of Enhancer of Zeste Homolog 2 (EZH2) and EZH1 designed to counter abnormal gene activity that may contribute to cancer development and progression, as well as drug resistance.
In September 2023, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for tulmimetostat for the treatment of patients with advanced, recurrent or metastatic endometrial cancer harboring AT-rich interacting domain containing protein 1A (ARID1A) mutations and who have progressed on at least one prior line of treatment.
Tulmimetostat is an Investigational Next-Generation EZH2/EZH1 Dual Inhibitor
Tulmimetostat is a once-daily oral therapy developed to inhibit the epigenetic regulators EZH2 and EZH1, with the aim of restoring normal gene expression. Tulmimetostat was designed to improve on first-generation EZH2 inhibitors through increased potency, longer residence time on target and a longer half-life, offering the potential for enhanced anti-tumor activity.
In a Phase 1/2 clinical study, tulmimetostat has shown preliminary anti-tumor activity in heavily pre-treated patients across solid tumors and lymphomas. An interim review of safety data suggests that the safety profile of tulmimetostat is consistent with EZH2 inhibitor class effects and with previous data; further study is warranted and ongoing.
Abnormal EZH2 and EZH1 Activity Promotes Cancer Development
EZH2 and EZH1 are proteins involved in the regulation of genes controlling cell division and cell death. Deviations in EZH2 activity can cause the atypical expression of these genes, which in turn can contribute to tumor development, growth and progression.
Patients with EZH2-mutated or overexpressing cancers often face poor prognoses. Furthermore, increases in EZH2 activity can contribute to the ability of cancer cells to develop resistance to therapies. If EZH2 is inhibited as part of targeted cancer therapies, EZH1 may compensate for EZH2 activity. Dual inhibition of EZH2 and EZH1 may have the potential to overcome current treatment limitations and improve outcomes for patients.