Advertisement Epizyme reports positive pre-clinical Phase I/II trial results of EPZ in synovial sarcoma - Pharmaceutical Business review
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Epizyme reports positive pre-clinical Phase I/II trial results of EPZ in synovial sarcoma

Epizyme has reported positive pre-clinical data from its Phase I/II trial of EPZ-6438 (E7438), its oral, small molecule inhibitor of EZH2, in models of synovial sarcoma, a soft tissue sarcoma that typically affects young adults.

EZH2 is a histone methyltransferase (HMT), which will play a potentially oncogenic role in a number of cancers such as germinal centre (GC) non-Hodgkin lymphomas, INI1-deficient cancers such as synovial sarcoma and malignant rhabdoid tumors, and a range of other solid tumors.

These tumors are characterized by a translocation of chromosomes X and 18, generating an SS18-SSX fusion protein that creates a state of deficiency of the INI1 protein.

Epizyme director of Biological Sciences Heike Keilhack said the data shows that EPZ-6438 induced anti-proliferative activity in three of four pre-clinical models of synovial sarcoma tested.

"The data continue to reinforce the importance of EZH2 inhibition in INI1-deficient malignancies, and warrant further investigation of EPZ-6438 in these genetically defined cancers," Keilhack said.

In the trial, synovial sarcoma cell lines and patient-derived xenograft models were evaluated for their sensitivity to EZH2 inhibition in vitro and in vivo.

The trial also assessed histone methylation, changes in gene expression and histology endpoints.

Results also showed that EPZ-6438 induced dose-dependent inhibition of cell growth and cell death specifically in SS18-SSX fusion-positive cells in vitro.

The company and its partner Eisai are developing EPZ-6438), a small molecule inhibitor of EZH2 created with its proprietary product platform, to treat patients with non-Hodgkin lymphoma.