CAMBRIDGE, MA, USA I October 17, 2014 I Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating innovative personalized therapeutics for patients with genetically defined cancers, today presented pre-clinical data on EPZ-6438 (E7438), its oral, small molecule inhibitor of EZH2, in models of synovial sarcoma, a soft tissue sarcoma that typically affects young adults. Synovial sarcomas 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. The data were presented by Heike Keilhack, Ph.D., Director of Biological Sciences, Epizyme, during the annual meeting of the Connective Tissue Oncology Society, held October 15-18 in Berlin, Germany. The poster is available on the Epizyme website at http://www.epizyme.com/wp-content/uploads/2014/10/E7438-CTOS-Poster.pdf.
“These data show that EPZ-6438 induced anti-proliferative activity in three of four pre-clinical models of synovial sarcoma tested,” said Dr. Keilhack. “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.”
In the study, synovial sarcoma cell lines and patient-derived xenograft models were evaluated for their sensitivity to EZH2 inhibition in vitro and in vivo. Histone methylation, changes in gene expression and histology endpoints were also assessed. The data showed that EPZ-6438 induced dose-dependent inhibition of cell growth and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice with either a cell line xenograft or two patient-derived xenograft models led to dose-dependent tumor growth inhibition, while treatment in a fourth xenograft model did not reflect such results.
About EZH2 Cancers
EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include germinal center (GC) non-Hodgkin lymphomas, INI1-deficient cancers such as synovial sarcoma and malignant rhabdoid tumors, and a range of other solid tumors.
About EPZ-6438
Epizyme and our partner Eisai are developing EPZ-6438 (Eisai refers to this therapeutic candidate as E7438), a small molecule inhibitor of EZH2 created with our proprietary product platform, for the treatment of non-Hodgkin lymphoma patients. In many human cancers, misregulated EZH2 enzyme activity results in misregulation of genes that control cell proliferation — without these control mechanisms, cancer cells are free to grow rapidly.
Epizyme granted Eisai a worldwide license to EPZ-6438 (E7438), subject to Epizyme’s right to opt in for co-development, co-commercialization and profit share arrangement with Eisai in the United States. Epizyme is working with Roche and Eisai to develop a companion diagnostic to identify patients with non-wild type EZH2, where EZH2 contains point mutations. Additional information about these partnerships may be found here: http://www.epizyme.com/about-us/partnerships/
In June 2013, Epizyme and Eisai initiated a Phase 1/2 clinical trial of EPZ-6438 (E7438) in patients with advanced solid tumors or B-cell lymphomas. EPZ-6438 is the second HMTi to enter human clinical development (following Epizyme’s DOT1L inhibitor, EPZ-5676).
Additional information about this program, including clinical trial information, may be found here: http://clinicaltrials.gov/ct2/show/NCT01897571?term=7438&rank=1
About Epizyme, Inc.
Epizyme, Inc. is a clinical stage biopharmaceutical company creating personalized therapeutics for patients with genetically defined cancers. Epizyme has built a proprietary product platform that the company uses to create small molecule inhibitors of a 96-member class of enzymes known as histone methyltransferases, or HMTs. HMTs are part of the system of gene regulation, referred to as epigenetics, that controls gene expression. Genetic alterations can result in changes to the activity of HMTs, making them oncogenic (cancer-causing). By focusing on the genetic drivers of cancers, Epizyme’s targeted science seeks to match the right medicines with the right patients for a personalized approach to cancer treatment.
SOURCE: Epizyme
Post Views: 102
CAMBRIDGE, MA, USA I October 17, 2014 I Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating innovative personalized therapeutics for patients with genetically defined cancers, today presented pre-clinical data on EPZ-6438 (E7438), its oral, small molecule inhibitor of EZH2, in models of synovial sarcoma, a soft tissue sarcoma that typically affects young adults. Synovial sarcomas 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. The data were presented by Heike Keilhack, Ph.D., Director of Biological Sciences, Epizyme, during the annual meeting of the Connective Tissue Oncology Society, held October 15-18 in Berlin, Germany. The poster is available on the Epizyme website at http://www.epizyme.com/wp-content/uploads/2014/10/E7438-CTOS-Poster.pdf.
“These data show that EPZ-6438 induced anti-proliferative activity in three of four pre-clinical models of synovial sarcoma tested,” said Dr. Keilhack. “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.”
In the study, synovial sarcoma cell lines and patient-derived xenograft models were evaluated for their sensitivity to EZH2 inhibition in vitro and in vivo. Histone methylation, changes in gene expression and histology endpoints were also assessed. The data showed that EPZ-6438 induced dose-dependent inhibition of cell growth and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice with either a cell line xenograft or two patient-derived xenograft models led to dose-dependent tumor growth inhibition, while treatment in a fourth xenograft model did not reflect such results.
About EZH2 Cancers
EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include germinal center (GC) non-Hodgkin lymphomas, INI1-deficient cancers such as synovial sarcoma and malignant rhabdoid tumors, and a range of other solid tumors.
About EPZ-6438
Epizyme and our partner Eisai are developing EPZ-6438 (Eisai refers to this therapeutic candidate as E7438), a small molecule inhibitor of EZH2 created with our proprietary product platform, for the treatment of non-Hodgkin lymphoma patients. In many human cancers, misregulated EZH2 enzyme activity results in misregulation of genes that control cell proliferation — without these control mechanisms, cancer cells are free to grow rapidly.
Epizyme granted Eisai a worldwide license to EPZ-6438 (E7438), subject to Epizyme’s right to opt in for co-development, co-commercialization and profit share arrangement with Eisai in the United States. Epizyme is working with Roche and Eisai to develop a companion diagnostic to identify patients with non-wild type EZH2, where EZH2 contains point mutations. Additional information about these partnerships may be found here: http://www.epizyme.com/about-us/partnerships/
In June 2013, Epizyme and Eisai initiated a Phase 1/2 clinical trial of EPZ-6438 (E7438) in patients with advanced solid tumors or B-cell lymphomas. EPZ-6438 is the second HMTi to enter human clinical development (following Epizyme’s DOT1L inhibitor, EPZ-5676).
Additional information about this program, including clinical trial information, may be found here: http://clinicaltrials.gov/ct2/show/NCT01897571?term=7438&rank=1
About Epizyme, Inc.
Epizyme, Inc. is a clinical stage biopharmaceutical company creating personalized therapeutics for patients with genetically defined cancers. Epizyme has built a proprietary product platform that the company uses to create small molecule inhibitors of a 96-member class of enzymes known as histone methyltransferases, or HMTs. HMTs are part of the system of gene regulation, referred to as epigenetics, that controls gene expression. Genetic alterations can result in changes to the activity of HMTs, making them oncogenic (cancer-causing). By focusing on the genetic drivers of cancers, Epizyme’s targeted science seeks to match the right medicines with the right patients for a personalized approach to cancer treatment.
SOURCE: Epizyme
Post Views: 102
