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Jun 23, 2011

The Leukemia & Lymphoma Society to Help Epizyme with Drug for Mixed Lineage Leukemia

  • The Leukemia & Lymphoma Society (LLS) and Epizyme will jointly support preclinical and Phase I development of the company’s therapy for mixed lineage leukemia (MLL). LLS will provide up to $7.5 million in milestone-based funding to Epizyme.

    The MLL drug candidate covered in this deal is a small molecule DOT1L-targeted histone methyltransferase inhibitor (HMTi). MLL patients are distinguished by the presence of a chromosomal alteration (MLL-translocation) that recruits DOT1L activity to aberrant gene locations.

    This results in increased expression of specific gene products that are known to drive leukemia cell proliferation. Epizyme’s investigational agent selectively kills MLL cells, while sparing cells that do not contain this chromosomal alteration.

    Epizyme says that its aim is to create personalized therapeutics for genetically defined oncology and rare disease patients. Its focus is small molecule inhibitors of histone methyltransferases.

    The company has one other program in its pipeline. EZH2 is in preclinical development for certain non-Hodgkin lymphomas and breast cancer subtypes. EZH2 targets the catalytic center of a multiprotein complex known as polycomb repressive complex 2 (PRC2). The PRC2 complex is responsible for placing three methyl groups on a specific histone lysine known as H3K27.

    In many human cancers, elevated levels of PRC2 enzyme activity cause hypertrimethylation of H3K27, resulting in the silencing of genes that otherwise control cell proliferation. Epizyme has discovered that specific mutations in the EZH2 enzyme are responsible for driving hypertrimethylation of H3K27, hence malignancy, in certain forms of non-Hodgkin lymphomas.


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