Our pipeline is led by tazemetostat, an internally developed, orally administered, first-in-class small molecule EZH2 inhibitor, for the treatment of multiple types of hematological malignancies and genetically defined solid tumors. We are currently conducting a comprehensive development program for tazemetostat designed to identify efficient and accelerated pathways to treat as many patients as may benefit.
We are investigating tazemetostat as a single-agent therapy in multiple clinical trials, including Phase 2 clinical trials in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), adult patients with certain genetically defined solid tumors, including INI1-negative tumors and synovial sarcoma, and patients with mesothelioma characterized by BAP loss of function. We are also conducting a clinical trial of tazemetostat in pediatric patients with certain genetically defined solid tumors, including INI1-negative tumors and synovial sarcoma.
Tazemetostat is also being evaluated in combinations and in additional indications, including:
- a combination study of tazemetostat with rituximab in patients with relapsed and/or refractory FL;
- a combination study of tazemetostat with R-CHOP in front-line patients in collaboration with the Lymphoma Study Association;
- a combination study of tazemetostat with the standards of care in patients with castration-resistant prostate cancer, and
- a combination study of tazemetostat with a PARP inhibitor in patients with platinum-resistant solid tumors, such as small-cell lung cancer, triple-negative breast cancer and ovarian cancer.
Epizyme holds global development and commercialization rights to tazemetostat ex-Japan. Eisai owns development and commercialization rights to tazemetostat in Japan, and a right of first negotiation to rights in the rest of Asia.
We are also investigating the potential of G9 inhibition for the treatment of hemoglobinopathies like sickle cell disease. It is widely understood within the SCD research community that elevation of fetal hemoglobin, which is normally silenced after birth, has disease-modifying potential for patients with β-globinopathies, such as SCD and β-thalassemia. To this end, multiple academic groups have previously discovered that inhibition of the histone methyltransferase (HMT) G9a led to increased levels of fetal hemoglobin in preclinical in vitro studies.
Building upon these findings, our scientists leveraged their expertise in HMT drug discovery to generate potent, selective inhibitors of G9a with drug-like properties.