Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP)
("Cyclacel" or the "Company"), a biopharmaceutical company
developing oral therapies that target various phases of cell cycle
control for the treatment of cancer and other serious disorders,
today announced the presentation of preclinical data demonstrating
that both Cyclacel’s CYC065, a clinical stage, second generation,
cyclin-dependent kinase CDK2/9 inhibitor, and CCT68127, a
preclinical stage CDK2/9 inhibitor, prolong survival in
MYCN-addicted neuroblastoma models. The data were presented at the
Childhood Cancer Meeting, September 5 – 7th in London, UK.
“This study adds to the growing evidence of the
value of CDK inhibition as an approach to treating cancer. MYCN is
an important therapeutic target in oncology and a major oncogenic
driver of neuroblastoma, a childhood cancer. There are no approved
drugs that act against MYCN or MYC proteins,” said Spiro Rombotis,
President and Chief Executive Officer of Cyclacel. “We are
encouraged by the preclinical data, which extend and support
earlier findings, showing that CYC065 and CCT68127 reduce MYCN
transcription and protein levels and have antitumor activity in
neuroblastoma models. Additionally, we have demonstrated in other
preclinical studies, that our transcriptional CDK2/9 inhibitors
target key molecular features of cancers with poor prognosis, such
as MLL-r leukemias or MYC-driven lymphomas. Furthermore, evidence
from early clinical trials show that CDK2/9 inhibitors can have a
synergistic effect with other anticancer agents. We look forward to
reporting data from our ongoing Phase 1 study of CYC065 in patients
with solid tumors.”
In this preclinical study, an international
group of researchers led by Prof. Louis Chesler from The Institute
of Cancer Research, London, explored in vitro and in vivo the
sensitivity of neuroblastoma cells to CYC065 and CCT68127.
Neuroblastoma cells with MYCN amplification and overexpression were
found to be particularly sensitive to both CDK2/9 inhibitors.
The mechanism of action of CYC065 and CCT68127 included inhibition
of MYCN transcription, downregulation of N-MYC protein, blocking
neuroblastoma cell proliferation and induction of apoptosis.
Treatment with either CYC065 or CCT68127 significantly reduced
tumor burden and prolonged survival in several neuroblastoma models
in vivo.
Citation
Poon E, Jamin Y, Walz S, Hakkert S, Kwok C,
Hallsworth A, Thway K, Barker K, Sbirkov Y, Pickard L, Urban Z,
Tardif N, Webber H, Box G, Valenti M, De Haven Brandon A, Petrie K,
Ebus M, Molenaar J, Eccles S, Robinson SP, Zheleva D, Eilers M,
Workman P, Chesler L. The small molecule CDK2 and CDK9 inhibitors
CYC065 and CCT68127 are potent inhibitors of MYCN via
transcriptional repression. Childhood Cancer Meeting 2016,
September 5 – 7th, London, UK, Abs. 1-19.
About MYCN
The MYCN gene encodes a transcription factor
that is expressed in fetal brain and neural crest and is critical
for normal development of the brain and nerves. The MYCN oncogene
is over-expressed in a number of different types of cancer, most
notably neuroblastoma, and also rhabdomyosarcoma, medulloblastoma,
astrocytoma, Wilms' tumor and small cell lung cancer. Amplification
of the MYCN oncogene is the most common genomic alteration in
aggressive neuroblastomas and is associated with poor clinical
outcome. There are no approved drugs that directly target MYCN
prompting the investigation of indirect approaches such as
exploitation of a synthetic lethal relationship between MYCN
amplification/overexpression and inhibition of CDK2.
About Neuroblastoma
According to the American Cancer Society,
neuroblastoma is the most common cancer in infants less than one
year old and it accounts for about six percent of all pediatric
cancers or about 700 cases per year. The disease has a fatal
outcome in one out of every seven children diagnosed with it.
Preclinical data from an international investigator group
demonstrated that Cyclacel’s CYC065 and CCT68127 target MYCN gene
expression and have potent in vitro and in vivo anti-tumor
activities, suggesting therapeutic potential in neuroblastoma,
including high-risk patients with MYCN amplification.
About CYC065
CYC065 is a highly-selective, orally- and
intravenously-available, second generation inhibitor of CDK2 and
CDK9 and causes apoptotic death of cancer cells at sub-micromolar
concentrations. Antitumor efficacy has been achieved in vivo with
once a day oral dosing at well tolerated doses. Evidence from
published nonclinical studies show that CYC065 may benefit patients
with adult and pediatric hematological malignancies, including
certain Acute Myeloid Leukemias (AML), Acute Lymphocytic Leukemias
(ALL), Chronic Lymphocytic Leukemias (CLL), B-cell lymphomas,
multiple myelomas, and certain solid tumors, including breast and
uterine cancers. Independent investigators published nonclinical
evidence that CYC065 induced regression or tumor growth inhibition
in a model of HER2-positive breast cancer addicted to cyclin E that
is resistant to trastuzumab, reduced tumor growth in models of
CCNE1-amplified uterine serous carcinoma and reduced tumor burden
and prolonged survival in several neuroblastoma models in vivo.
CYC065 is mechanistically similar but has much
higher dose potency, in vitro and in vivo, improved metabolic
stability and longer patent protection than seliciclib, Cyclacel's
first generation CDK inhibitor. Translational biology data support
development of CYC065 as a stratified medicine for solid and liquid
cancers. CYC065 has been shown to reverse drug resistance
associated with the addiction of cancer cells to cyclin E and may
inhibit CDK9-dependent oncogenic and leukemogenic pathways,
including malignancies driven by certain oncogenes and mixed
lineage leukemia rearrangements (MLL-r). CYC065 causes prolonged
down regulation of the Mcl-1-mediated pro-survival pathway in
cancer cells.
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.
Cyclacel's pipeline includes an oral combination of sapacitabine
and seliciclib (CDK2/9 inhibitor) in Phase 1 in advanced solid
tumors including patients with BRCA mutations; sapacitabine in
Phase 2 in MDS; and CYC065 (CDK2/9 inhibitor) in Phase 1 in solid
tumors with potential utility based on preclinical data in other
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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