Cyclacel Pharma (CYCC) Announces Presentation of Encouraging Preclinical CYC140 Data
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Cyclacel Pharmaceuticals, Inc. (Nasdaq: CYCC) (Nasdaq: CYCCP) announced the presentation of preclinical data demonstrating the therapeutic potential of the Company's novel polo-like kinase (PLK) 1 inhibitor, CYC140, as a targeted anti-cancer agent. The data demonstrates that CYC140 is a selective PLK1 inhibitor which preferentially induces growth inhibition and cell death in malignant versus non-malignant cells. The data were presented at the 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany.
“CYC140 is a selective and potent inhibitor of PLK1, an important cancer therapy target. We selected this promising targeted molecule as a clinical candidate after completing IND-enabling studies,” said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. “Data presented at EORTC-NCI-AACR highlights CYC140’s potential as an agent to treat a variety of cancer indications, including esophageal cancer and acute leukemia. We look forward to making an Investigational New Drug submission with the goal of initiating a first-in-human Phase 1 trial. In the meantime we continue to progress our later stage programs, including our Phase 3 SEAMLESS study with oral sapacitabine capsules, where we anticipate reporting top line results late in the fourth quarter of 2016 or in early 2017."
Treatment of proliferating cells with CYC140 resulted in reduced phosphorylation of the PLK1 substrate phospho-nucleophosmin, accumulation of cells in mitosis and increase in the proportion of mitotic cells with monopolar spindles, all features consistent with PLK1 inhibition. In a cell line panel derived from esophageal cancer and various non-malignant solid tissues, CYC140 was preferentially cytotoxic to malignant cells. Its differential cytotoxicity is further increased through pulse treatment. Malignant cells which are sensitive to CYC140 undergo complete growth inhibition and induction of cell death in response to treatment. In contrast, non-malignant cells are only temporarily arrested and normal cell cycle transit is restored.
Potent anti-tumor activity of CYC140 has been demonstrated in preclinical xenograft models of acute leukemia and solid tumors, including esophageal cancer, with tumor growth delay, tumor regression and cures being observed. Identification of several pharmacodynamic markers and demonstration of activity in a majority of malignant cell lines derived from acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and esophageal cancer support prospective clinical development of CYC140, alone and in several potential combinations with targeted agents.
|Title:||Therapeutic potential of novel PLK1 inhibitor, CYC140, in esophageal cancer and acute leukemia|
|Date/Time:||Thursday, December 1, 2016: 10:15 a.m. – 5:00 p.m. UTC+1|
|Location:||Poster Board P034|
|Authors:||S. Moureau, E. Pohler, K. Kroboth, C. Saladino, C. MacKay, J. Hollick, D. Zheleva, S. Frame, D. Blake, Cyclacel Ltd, Dundee, Scotland, UK|
The abstract can be accessed through the EORTC-NCI-AACR website, http://www.ecco-org.eu/ENA2016.
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