- Preclinical Data Presented at the AACR 2017
Meeting -
Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC) (NASDAQ:CYCCP)
(Cyclacel or the Company), today announced the presentation of
preclinical data outlining the potential therapeutic utility of
CYC140, a polo-like kinase (PLK) 1 inhibitor, for the treatment of
esophageal cancer and acute leukemia. The findings were presented
during the American Academy of Cancer Research (AACR) Annual
Meeting, April 1-5, in Washington, D.C.
“We believe these findings further validate the
potential utility of CYC140 and its selection as a clinical
candidate,” said Spiro Rombotis, President and Chief Executive
Officer of Cyclacel. “CYC140 is a potent and selective inhibitor of
PLK1, an oncogenic regulator of cell division. These preclinical
data suggest that CYC140 can be targeted against esophageal cancer
and acute leukemia. In addition, the data demonstrate the potential
for CYC140 to be used in synergistic combinations with other
targeted agents, including EGFR inhibitors and PI3K pathway
inhibitors, to enhance cancer cell death or growth suppression.
CYC140 was discovered and developed in-house, drawing on our strong
scientific experience in cell cycle biology. Based on these results
and the conclusion of IND-directed development we plan to make an
Investigational New Drug submission for CYC140.”
Esophageal cancer and acute leukemia were
identified as highly sensitive cancer indications from a panel of
300 cancer cell lines and non-malignant comparators following short
exposure to CYC140. CYC140 demonstrated good selectivity over
non-malignant cell lines. Potent, dose-dependent antitumor activity
of CYC140 was demonstrated in preclinical xenograft models of
esophageal cancer and acute leukemia with tumor growth delay, tumor
regression and cures observed.
In esophageal cancer cell lines CYC140 combined
synergistically with EGFR inhibitors or PI3K pathway inhibitors and
can also be combined with approved cytotoxics such as cisplatin.
Consistent with PLK1 inhibition, CYC140 reduced phosphorylation of
nucleophosmin, a PLK1 substrate, and caused accumulation of mitotic
cells in vitro and in vivo.
The study concluded that CYC140 is a selective
PLK1 inhibitor which preferentially induces growth inhibition and
cell death in malignant versus non-malignant cells. 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 potential combination with targeted agents.
Abstract: |
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4178 |
Title: |
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The novel PLK1 inhibitor,
CYC140: Identification of pharmacodynamic markers, sensitive target
indications and potential combinations |
Date/Time: |
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Tues. April 4, 2017: 1
p.m. - 5 p.m. EDT |
Location:
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Section 7, Poster Board
1 |
Session
Title: |
Targeting Protein Kinases
and DNA |
Authors: |
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Sylvie Moureau, Craig
MacKay, Chiara Saladino, Elizabeth Pohler, Karin Kroboth, Jonathan
Hollick, Daniella Zheleva, Sheelagh Frame, David Blake. Cyclacel
Ltd, Dundee, United Kingdom |
The abstract can be accessed through the AACR
website, www.aacr.org.
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, transcriptional
regulation and DNA damage response biology to develop innovative,
targeted medicines for cancer and other proliferative diseases.
Cyclacel's transcriptional regulation program is evaluating CYC065,
a CDK inhibitor, in patients with advanced cancers. The DNA damage
response program is evaluating a sequential regimen of sapacitabine
and seliciclib, a CDK inhibitor, in patients with BRCA positive,
advanced solid cancers. Cyclacel is analyzing stratified and
exploratory subgroups from a Phase 3 study of sapacitabine in
elderly patients with AML. Cyclacel's strategy is to build a
diversified biopharmaceutical business focused in hematology and
oncology based on a pipeline of novel drug candidates. For
additional information, please visit www.cyclacel.com.
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 which 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 2017 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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