Cyclacel Announces Presentation of Molecular Rationale for Clinical Development of CYC065 CDK Inhibitor in Leukemias, Lymphomas

Cyclacel Pharmaceuticals, Inc. CYCC CYCCP ("Cyclacel" or the "Company"), today announced the presentation of preclinical data demonstrating the molecular rationale for the clinical development of CYC065, Cyclacel's second-generation cyclin dependent kinase (CDK) inhibitor, to treat hematological malignancies, including acute leukemias and lymphomas. The data showed that a range of CDK9-dependent acute myelogenous leukemia (AML) and diffuse large B-cell lymphoma (DLBCL) cell lines were sensitive to CYC065. The cell line panel represented different genetic characteristics of hematological malignancies correlating with poor prognosis, including MLL rearrangements (MLLr) and myc amplification or overexpression. CYC065 was also shown to combine effectively with standard cytotoxic agents, such as cytarabine, and with agents targeting apoptotic regulators, including Bcl-2 inhibitors, such as venetoclax (ABT-199/GDC-0199). The data were presented at the Society of Hematologic Oncology (SOHO) 2015 Annual Meeting taking place September 16-19, 2015 in Houston, Texas. "CDK inhibition is emerging as an important therapeutic approach in a number of cancer types," said Spiro Rombotis, Cyclacel's President and Chief Executive Officer. "The mechanism of action of CYC065 targets key molecular features of hematological cancers, such as MLLr leukemias or myc-driven lymphomas, diseases with high unmet medical need. In addition, we have identified both approved and investigational anticancer agents which have a synergistic effect when combined with CYC065. We are encouraged by the evidence that CYC065 has promising anticancer activity as a single agent in sensitive cancers and that it can counter drug resistance mechanisms in combination with other anticancer agents. Our IND for CYC065 has been cleared by the FDA and we look forward to dosing the first patient in our first-in-human Phase 1 clinical trial." The study (Poster no. 213) demonstrated the molecular rationale for clinical development of CYC065 in hematological malignancies. The anticancer activity of CYC065 was evaluated in in vitro assays of human AML, acute lymphoblastic leukemia (ALL) and DLBCL cell lines to assess CYC065's mechanism of action and determinants of cellular sensitivity. CYC065 induced rapid apoptosis by inhibition of expression of CDK9-dependent oncogenic transcripts, including MCL-1, c-myc, Hoxa9 and Meis1. Cell line sensitivity correlated with levels of Bcl-2 family proteins, which regulate apoptosis. CYC065 was highly synergistic in combination with Bcl-2 inhibitors in both AML and DLBCL lines. CYC065's potent anticancer activity has been confirmed in AML xenograft animal models in which tumor growth inhibition ranging from 90 to 97 percent was achieved at well-tolerated dose levels.