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CYCLACEL PHARMACEUTICALS PRESENTS INSIGHTS INTO THE MECHANISMS OF ITS CELL
CYCLE INHIBITOR DRUGS
-- Preclinical Data on Cyclacel’s Cell Cycle Inhibitors Presented at
American Association for Cancer Research Annual Meeting --
BERKELEY HEIGHTS, NJ, April 16, 2008 –
Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP) and independent
investigators presented eight posters at the annual meeting of the American
Association for Cancer Research (AACR) with preclinical data demonstrating the
ability of Cyclacel’s cell cycle inhibitors to induce cancer cell death, or
apoptosis, by inhibiting key enzymes. Five of these preclinical studies
evaluated Cyclacel’s CYC116 cell cycle inhibitor. The studies provide additional
evidence that CYC116 inhibits Aurora kinases and Vascular Endothelial Growth
Factor Receptor-2 tyrosine kinase or VEGFR-2 kinase. Aurora kinases are target
proteins that are essential for mitosis or the process by which a cell divides.
VEGFR-2 kinase is a validated target promoting angiogenesis or new vessel
formation in the vicinity of cancer cells.
“The preclinical data presented at AACR support our understanding that CYC116
has both anti-mitotic and anti-angiogenic activity and help direct our
development plan for this drug candidate,” said Gregory Reyes, M.D., Ph.D.,
Senior Vice President Research for Cyclacel Pharmaceuticals. “The ability of
CYC116 to target both Aurora and VEGFR2 kinases suggests that it may have
potential utility in a range of solid tumors and also hematologic malignancies.”
CYC116 is a novel, ATP-competitive, pyrimidine drug that is taken by mouth as a
capsule. The drug is a selective agent that potently inhibits the enzymes Aurora
kinases and VEGFR-2 kinase at comparable levels with a range of 19 to 69
nanomolar. Median potency of CYC116 in cancer cells is approximately 300
nanomolar. CYC116 has demonstrated a broad spectrum of potent cytotoxic activity
against human tumor cell types. Non-clinical efficacy of CYC116 has been
demonstrated by the oral route using mouse leukemia models, in which increased
survival was observed, and human solid tumor xenograft models, in which
reductions in tumor growth were observed. Cancer cell types that appear to be
particularly sensitive to CYC116 are leukemia, non-small cell lung cancer and
pancreatic cancer.
CYC116 works by affecting the cell cycle progression of cancer cells before they
enter mitosis or divide to create daughter cancer cells. The mechanism of action
of CYC116 affects cancer cells in several ways. CYC116-treated cells display
delayed entry into mitosis; defective polymerization of tubulins, or proteins
that make up microtubules which are the target of the taxane drugs; changes in
the function of the centrosome, or the cell’s microtubule organizing center; and
formation of the mitotic spindle, or the highway along which chromosomes and
cellular materials are transported from the mother cell to the daughter cells.
After cancer cells are treated with CYC116, their spindle checkpoint is
inactivated resulting in inhibition of cytokinesis or the process by which a
mother cell divides. These defects result in the generation of polyploidy or
cells with more than two chromosome sets, multinucleated cells or cells with
multiple cores and apoptosis or cancer cell death.
In a mouse model of leukemia CYC116-treatment induced decreases in tumor cell
volume and infiltration of leukemic cells in the bone marrow and resulted in an
increase in life span. No significant effects on body weight or normal bone
marrow cells were observed at effective doses of CYC116. Tumor
neovascularization, or creation of new blood vessels around a tumor, was
significantly reduced in a dose dependent manner. The data confirm that CYC116
acts as a dual mitotic and angiogenesis inhibitor, a combination of anti-cancer
mechanisms which could have therapeutic benefit in the clinic.
CYC116 is currently being studied in a Phase 1 trial in patients with solid
tumors at Roswell Park Cancer Institute in Buffalo, New York, and South Texas
Accelerated Research Therapeutics (START) in San Antonio. The study is designed
to identify the maximum tolerated dose of CYC116 and evaluate its
pharmacokinetic, pharmacodynamic and anti-tumor effects.
Details of the poster presentations referring to specific Cyclacel programs are
as follows:
Sapacitabine
“Impact of DNA repair proteins on cell survival in response to damage induced by
the DNA self-strand-breaking nucleoside analogue CNDAC”*
Date/Time: Sunday, Apr 13, 2008, 8:00 AM - 12:00 PM
Abstract Number: 638
Seliciclib
“Optimal cancer chronotherapeutics schedules of seliciclib revealed by a systems
biology approach”*
Date/Time: Sunday, Apr 13, 2008, 1:00 PM - 5:00 PM
Abstract Number: 801
“Potential therapeutic role of seliciclib in combination with ionizing radiation
for human nasopharyngeal carcinoma”
Date/Time: Wednesday, April 16, 2008, 8:00 AM – 12:00 PM PST
Abstract Number: 5511
CYC116
“The basis of cell sensitivity to Aurora A/B inhibitors”
Date/Time: Sunday, April 13, 2008, 8:00 AM – 12:00 PM PST
Abstract Number: 651
“Systems biology analysis of a novel Aurora kinase inhibitor: CYC116”
Date/Time: Monday, April 14, 2008, 8:00 AM – 12:00 PM PST
Abstract Number: 1645
“Combination studies with the oral Aurora kinase inhibitor CYC116 and
chemotherapeutic agents”
Date/Time: Tuesday, April 15, 2008, 8:00 AM – 12:00 PM PST
Abstract Number: 4015
“In vivo mode of action of CYC116, a novel small molecule inhibitor of Aurora
kinases and VEGFR2”
Date/Time: Wednesday, April 16, 2008, 8:00 AM – 12:00 PM PST
Abstract Number: 5645
“Anti-tumor activity of CYC116, a novel small molecule inhibitor of Aurora
kinases and VEGFR2”
Date/Time: Wednesday, April 16, 2008, 8:00 AM – 12:00 PM PST
Abstract Number: 5644
The abstracts are currently available online at
www.aacr.org .
*Note: asterisks denote research conducted by independent investigators.
About Cyclacel Pharmaceuticals, Inc.
Cyclacel is a biopharmaceutical company dedicated to the discovery, development
and commercialization of novel, mechanism-targeted drugs to treat human cancers
and other serious disorders. Three Cyclacel drugs are in clinical development.
Sapacitabine (CYC682), an orally-available cell cycle modulating nucleoside
analog, is in Phase 2 studies for the treatment of acute myeloid leukemia in the
elderly and cutaneous T-cell lymphoma (CTCL). Seliciclib (CYC202), an
orally-available CDK (cyclin dependent kinase) inhibitor, is in Phase 2 for the
treatment of lung cancer and nasopharyngeal cancer. CYC116, an orally-available,
Aurora kinase and VEGFR2 inhibitor, is in Phase 1 in patients with solid tumors.
Several additional programs are at an earlier stage. Cyclacel’s ALIGN
Pharmaceuticals subsidiary markets directly in the U.S. Xclair™ Cream for
radiation dermatitis, Numoisyn™ Liquid and Numoisyn™ Lozenges for xerostomia.
Cyclacel’s strategy is to build a diversified biopharmaceutical business focused
in oncology, hematology and other therapeutic areas based on a portfolio of
commercial products and a development pipeline of novel drug candidates.
Please visit www.cyclacel.com for additional information. Note: The Cyclacel
logo and Cyclacel® are trademarks of Cyclacel Pharmaceuticals, Inc. Numoisyn™
and Xclair™ are trademarks of Sinclair Pharma plc.
Risk Factors
This news release contains certain forward-looking statements that involve risks
and uncertainties that could cause actual results to be materially different
from historical results or from any future results expressed or implied by such
forward-looking statements. Such forward-looking statements include statements
regarding, among other things, the efficacy, safety, and intended utilization of
Cyclacel's product candidates, the conduct and results of future clinical
trials, plans regarding regulatory filings, future research and clinical trials
and plans regarding partnering activities. Factors that may cause actual results
to differ materially include the risk that product candidates that appeared
promising in early research and clinical trials do not demonstrate safety and/or
efficacy in larger-scale or later clinical trials, the risk that Cyclacel will
not obtain approval to market its products, the risks associated with reliance
on outside financing to meet capital requirements, and the risks associated with
reliance on collaborative partners for further clinical trials, development and
commercialization of product candidates. You are urged to consider statements
that include the words "may," "will," "would," "could," "should," "believes,"
"estimates," "projects," "potential," "expects," "plans," "anticipates,"
"intends," "continues," "forecast," "designed," "goal," or the negative of those
words or other comparable words to be uncertain and forward-looking. These
factors and others are more fully discussed under "Risk Factors" in the Annual
Report on Form 10-K for the year ended December 31, 2007, as supplemented by the
interim quarterly reports, filed with the SEC.
Contacts for Cyclacel:
Cyclacel Pharmaceuticals, Inc. WeissComm Partners
Corey Sohmer Aline Schimmel
(908) 517-7330 (312) 284-4706
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