Personalized Medicine Potential of Cyclacel's Innovative and Diverse Oncology Pipeline Highlighted at NCRI Cancer …

Posted: November 7, 2012 at 2:50 pm

BERKELEY HEIGHTS, N.J., Nov. 6, 2012 (GLOBE NEWSWIRE) -- Cyclacel Pharmaceuticals, Inc. (CYCC) (CYCCP) (Cyclacel or the Company), announced today multiple posters presented on the Company's sapacitabine and on its Polo-Like Kinase 1 (Plk1) inhibitors during the 8th National Cancer Research Institute (NCRI) Cancer Conference being held November 4-7, 2012, Liverpool, United Kingdom.

Sapacitabine:

"Sapacitabine efficacy is enhanced in homologous recombination defective tumours" Date/Time: Tuesday November 6, 2012, 8:30 -- 17:30 Greenwich Mean Time Poster Number: B21

Cyclacel researchers reported that in vitro studies of sapacitabine's active metabolite CNDAC showed that sapacitabine may be effective in patients with mutations of the breast cancer susceptibility proteins BRCA1/2 or homologous recombination repair (HRR)-deficient tumors, such as subsets of triple negative breast, ovarian, colon and non-small cell lung cancer (NSCLC). In addition, CNDAC synergized with either PARP inhibitors or cisplatin in both NSCLC and ovarian cancer cell lines. Cyclacel's cyclin-dependent kinase (CDK) inhibitor seliciclib reduces expression of BRCA1 and BRCA2 and can potentiate sapacitabine/CNDAC activity, as well as other agents enhanced in double strand break (DSB) repair-defective backgrounds. Sapacitabine treatment in combination with seliciclib is currently under investigation in a Phase 1 trial in patients with solid tumors at the Dana Farber Cancer Institute (Boston, MA).

"Therapeutic potential of sapacitabine in cancers defective in homologous recombination" Date/Time: Tuesday November 6, 2012, 8:30 -- 17:30 Greenwich Mean Time Poster Number: B207

Cyclacel collaborators from the Northern Institute for Cancer Research, Newcastle University, UK reported confirmation that ovarian and breast cancer cell lines defective in HRR are highly sensitive to CNDAC, supporting a possible role for sapacitabine/CNDAC in HRR-defective diseases. Primary ovarian cancer samples were also highly sensitive to CNDAC, and correlation of HRR status with CNDAC sensitivity is being assessed.

The studies further support the potential for sapacitabine to be used alone or in combinations to treat HRR- defective tumors, such as ATM- or BRCA-defective tumors. An investigator-sponsored Phase 2 study of sapacitabine in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) with deletion 11q22-23 is ongoing at The University of Texas MD Anderson Cancer Center (Houston, TX). A Phase 1, study of sapacitabine in combination with seliciclib in patients with advanced solid tumors, is ongoing at the Dana Farber Cancer Institute (Boston, MA). As reported at the American Society of Clinical Oncology 2012 annual meeting among 19 patients in this study treated at the recommended Phase 2 doses, 3 with advanced breast, ovarian and pancreatic cancer achieved partial responses (PRs) and 1 with ovarian cancer showed stable disease. All 4 responding patients were reported by the investigator to be BRCA defective.

Polo-Like Kinase 1 (Plk1) inhibitors:

"Parameters improving the therapeutic window of Compound 4, a potent and selective Polo-like kinase 1 inhibitor: in vitro studies" Date/Time: Tuesday November 6, 2012, 8:30 -- 17:30 Greenwich Mean Time Poster Number: B15

Cyclacel scientists and academic collaborators reported the biological characterization of Compound 4, a potent and selective, preclinical-stage, Plk1 inhibitor, selected for further development from Cyclacel's novel Plk1 inhibitor series. In a panel of esophageal cancer cell lines, sensitivity to Compound 4 correlated with p53 status. Esophageal cell lines lacking functional p53 showed the greatest sensitivity to Compound 4. Short drug exposure times demonstrated differential sensitivity between cancerous esophageal cells versus control, outlining the potential broad therapeutic index for Compound 4 in treating esophageal cancers, and in particular those with non-functional p53. Status of p53 could be used as a predictive biomarker in clinical trials to identify responders.

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Personalized Medicine Potential of Cyclacel's Innovative and Diverse Oncology Pipeline Highlighted at NCRI Cancer ...

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