Cyclacel’s Novel PLK1 Inhibitor, CYC140, Demonstrates Therapeutic Potential in Esophageal Cancer and Acute Leukemia
December 01 2016 - 7:00AM
Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP)
("Cyclacel" or the "Company"), a biopharmaceutical company
developing oral therapies that target the various phases of cell
cycle control for the treatment of cancer and other serious
disorders, today 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.
Abstract: |
355 |
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 |
Session Title: |
‘Cytotoxics’ |
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.
About PLK inhibition
Polo kinases were discovered by Professor David
Glover, Cyclacel’s Chief Scientist. They are a family of enzymes
that regulate cell cycle progression through mitosis or cell
division. PLKs are part of the biological machinery that regulate
spindle formation and activation of CDK/cyclin complexes during
mitosis. Activity of the mitotic kinase PLK1 is strongly
associated with cancer progression. Several studies have shown
correlations between elevated PLK1 expression, histological grade
and poor prognosis in several types of cancer. PLK1 may have a role
in oncogenesis through its regulation of tumor suppressors, such as
p53 and BRCA2. Inhibition of PLK1 by small molecules or siRNA has
been shown to interfere with several stages of mitosis. PLK1
inhibition offers an opportunity to treat cancer with a targeted
anti-mitotic approach.
ABOUT CYC140
Cyclacel employed high throughput screening, in
silico screening and de novo ligand design approaches to discover
multiple PLK1 inhibitor series. The lead series includes potent and
highly selective PLK1 inhibitors with broad anti-proliferative
activity across a range of tumor cell lines, which are highly
active in xenograft models of human cancers when dosed
orally. CYC140 was selected as a clinical candidate following
optimization for drug-like properties, cellular activity and
pharmacokinetic profile. CYC140 has recently completed IND-enabling
studies.
A grant of approximately $3.7 million from the U.K. Government's
Biomedical Catalyst has supported IND-directed development of
CYC140.
About Cyclacel Pharmaceuticals, Inc.
Cyclacel Pharmaceuticals is a clinical-stage
biopharmaceutical company using cell cycle control and DNA damage
response biology to develop innovative, targeted medicines for
cancer and other proliferative diseases. The SEAMLESS randomized
Phase 3 trial of sapacitabine as front-line treatment for AML in
the elderly under an SPA with FDA has completed enrollment and
follow-up. Cyclacel's pipeline includes an oral combination of
seliciclib (CDK inhibitor) and sapacitabine in Phase 1 in advanced
solid tumors, including patients with BRCA mutations; sapacitabine
in Phase 2 in MDS; and CYC065 (CDK inhibitor) in Phase 1 in solid
tumors with potential utility based on preclinical data also in
hematological malignancies. Cyclacel's strategy is to build a
diversified biopharmaceutical business focused in hematology and
oncology based on a pipeline of novel drug candidates. Please visit
www.cyclacel.com for more information.
FORWARD LOOKING STATEMENTS
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, trials may have difficulty enrolling,
Cyclacel may not obtain approval to market its product candidates,
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. For a
further list and description of the risks and uncertainties the
Company faces, please refer to our most recent Annual Report on
Form 10-K and other periodic and other filings we file with the
Securities and Exchange Commission and are available at
www.sec.gov. Such forward-looking statements are current only as of
the date they are made, and we assume no obligation to update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
© Copyright 2016 Cyclacel Pharmaceuticals, Inc.
All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks
of Cyclacel Pharmaceuticals, Inc.
CONTACTS
Company: Paul McBarron, (908) 517-7330, pmcbarron@cyclacel.com
Investor Relations: Russo Partners LLC, Alexander Fudukidis, (646) 942-5632, alex.fudukidis@russopartnersllc.com
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