Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC) (NASDAQ:CYCCP)
("Cyclacel" or the "Company"), today announced the presentation by
independent investigators of preclinical data demonstrating
therapeutic potential of CYC065, the Company's second-generation,
cyclin-dependent kinase (CDK) 2/9 inhibitor, as a targeted
anti-cancer agent. The data show that CYC065 substantially
inhibited growth, triggered apoptosis, and induced anaphase
catastrophe in murine and human lung cancer cells with known high
metastatic potential. This was in marked contrast to effects in
immortalized pulmonary epithelial murine and human cells. CYC065
markedly inhibited migration and invasion of lung cancer cells and
affected distinctive pathways involved in DNA damage response,
apoptosis, cell cycle regulation and cell migration. The data were
presented at the American Association for Cancer Research (AACR)
Annual Meeting 2017, April 1 - 5, 2017, in Washington, D.C.
"This study adds to the growing evidence of the
value of CDK inhibition as an approach to treating cancer,” said
Spiro Rombotis, President and Chief Executive Officer of Cyclacel.
“CYC065 is in a Phase 1, first-in-human trial to evaluate safety,
tolerability and pharmacokinetics in patients with solid tumors.
The trial is at an expanded sixth dose escalation level with the
objective of determining maximum tolerated dose and recommended
dosing for Phase 2. Evidence of target engagement with prolonged
Mcl-1 suppression in peripheral blood cells has been observed in
patient samples from the study. We believe that CYC065 is one
of the first medicines to demonstrate this in a human trial and
look forward to pursuing this lead as part of our transcription
regulation program.”
In the preclinical study, a group of researchers
led by Professor Ethan Dmitrovsky, M.D., including Masanori
Kawakami M.D., Ph.D., from The University of Texas MD Anderson
Cancer Center, Houston, Texas, explored whether CYC065’s
antineoplastic effects engaged anti-metastatic pathways. In vitro
migration and invasion assays showed that CYC065 markedly inhibited
migration and invasion of lung cancer cell lines, including KRAS
mutant line. Reverse Phase Protein Arrays (RPPA) interrogated
nearly 300 growth-regulatory proteins in murine and human lung
cancer.
CYC065 treatment resulted in up-regulation of
proteins involved in DNA damage and apoptosis, and down-regulation
of ones involved in mTOR- and integrin pathways. Ingenuity pathway
analysis (IPA) revealed up-regulation of pathways that engaged ATM
signaling, G2/M DNA damage checkpoint regulation, or apoptosis
signaling, down-regulation of pathways involved in mTOR signaling,
cell cycle regulation, or integrin–mediated cell migration.
Data presented at AACR show CYC065’s potential to
cause anaphase catastrophe and to inhibit migration and invasion of
lung cancer cells including the one with mutant KRAS.
Anaphase catastrophe is a novel mechanism of action which offers an
innovative approach to combat aneuploid cancer cells containing
abnormal numbers of chromosomes. The data highlight CYC065’s
potential to target key molecular features of cancers.
The study concluded that CYC065 elicits marked
antineoplastic effects in lung cancers despite presence of KRAS
mutations through anaphase catastrophe and also inhibited migration
and invasion of lung cancer cells.
Abstract: |
128 |
Title: |
The next
generation CDK2/9 inhibitor CYC065 elicits marked antineoplastic
effects in lung cancer by engaging anti-metastatic pathways |
Date/time: |
Sunday,
April 2, 2017 1:00 – 5:00 p.m. ET |
Location: |
Section 5,
Poster Board 24 |
Session Title: |
Novel
Agents |
Authors: |
Masanori
Kawakami1, Jason Roszik2,3, Lin Zheng1, Jonathan Kurie1, Lisa Maria
Mustachio1, Xi Liu1, Ethan Dmitrovsky1 1. Department of
Thoracic/Head and Neck Medical Oncology, 2. Genomic Medicine,
3.Cancer Biology; The University of Texas MD Anderson Cancer
Center, Houston, Texas. |
The abstract can be accessed through the AACR website,
www.aacr.org.
About CYC065
Cyclacel's second generation CDK2/9 inhibitor, CYC065, is being
evaluated in an ongoing, first-in-human, Phase 1 trial in patients
with advanced solid tumors. In addition to determining safety and
recommended dosing for Phase 2, the study aims to investigate
CYC065's effects on the Mcl-1 biomarker, which is implicated in the
evolution of resistance in cancer. Evidence of target engagement
with prolonged Mcl-1 suppression in peripheral blood cells was
observed in patient samples from the study, as well as decreases in
kinase substrate phosphorylation and increases in PARP cleavage,
consistently with the Company's preclinical data. CYC065 is
mechanistically similar but has much higher dose potency, in vitro
and in vivo, and improved metabolic stability than seliciclib,
Cyclacel's first generation CDK inhibitor. Similar to
palbociclib, the first CDK inhibitor approved by FDA in 2015,
CYC065 may be most useful as a therapy for patients with both
liquid and solid tumors in combination with other anticancer
agents, including Bcl-2 antagonists, such as venetoclax, or HER2
inhibitors, such as trastuzumab.
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 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 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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