Cyclacel Pharma Reports CYC065 CDK Inhibitor Shows Terapeutic Potential in Acute Leukemias with MLL Rearrangements

Cyclacel Pharmaceuticals, Inc.

("Cyclacel" or the "Company"), today announced the presentation of preclinical data demonstrating the therapeutic potential of CYC065, Cyclacel's second-generation cyclin dependent kinase (CDK) inhibitor, to treat acute leukemias, and in particular those with rearrangements in the mixed lineage leukemia (MLL) gene. The data showed that in vitro all human acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) cell lines with MLL rearrangements (MLLr) tested were sensitive to CYC065 and that the drug inhibited MLL-driven gene expression. Potent anticancer activity of CYC065 was demonstrated in vivo in AML xenograft models resulting in over 90% inhibition of tumor growth. The data were presented at the 2014 Society of Hematologic Oncology (SOHO) meeting taking place September 17-20, 2014 in Houston, Texas. "CDK inhibition is emerging as an important therapeutic approach in a number of tumor types," said Spiro Rombotis, Cyclacel's President and Chief Executive Officer. "MLL rearrangements identified in AML or ALL patients are associated with a poor prognosis. CYC065 works by targeting CDK enzymes which are key components of MLLr cell survival and resistance to chemotherapy. We are encouraged by the data reported, as they provide evidence that CYC065 has promising anticancer activity, especially in AML or ALL with MLL rearrangements, and that it can counter drug resistance mechanisms. CYC065 has completed IND-directed drug development and we look forward to advancing it into clinical trials." The study (Poster no. 209) evaluated the anticancer activity of CYC065 in in vitro assays of human AML and ALL cell lines with normal and mutated MLL gene status, CYC065's mechanism of action and determinants of cellular sensitivity. CYC065 induced rapid apoptosis and inhibited MLL-driven transcription of genes involved in leukemia stem cell biology. Cell line sensitivity correlated with the levels of proteins from the Bcl-2 family, which regulate apoptosis, and combining CYC065 with Bcl-2 inhibitors was synergistic in all tested leukemia lines. CYC065's potent anti-cancer activity was confirmed in AML xenograft models in which tumor growth inhibition ranging from 90 to 97 percent was achieved at well-tolerated dose levels.