Cyclacel Pharmaceuticals, Inc. (Nasdaq: CYCC) (Nasdaq: CYCCP)
(Cyclacel or the Company), a biopharmaceutical company developing
innovative medicines based on cancer cell biology, today announced
publication of a peer-reviewed study of fadraciclib, in PLOS ONE.
The publication, authored by scientists from Cyclacel and The
Institute of Cancer Research, London, describes the discovery of
fadraciclib and shows its ability to target CDK2 and CDK9, leading
to broad therapeutic potential.
“The published findings strengthen the
mechanistic rationale for fadraciclib’s potential as an anti-cancer
therapy. Building upon previous research in CDK pathways, including
the roles of cyclin E, MCL1 and MYC overexpression, the paper
highlights the benefits of inhibiting both CDK2 and CDK9, two
complementary cancer pathways,” said Spiro Rombotis, President and
Chief Executive Officer of Cyclacel. “Independent findings reported
at the ASCO20 Virtual Scientific Program corroborate the
attractiveness of this dual targeting approach. Based on recently
disclosed clinical data fadraciclib is establishing a leadership
position among apoptosis enabling compounds in clinical
development. We are encouraged by observations of single agent
anticancer activity in our clinical studies. Initial clinical data
with oral fadraciclib show concordance with intravenous
pharmacokinetics. In parallel with evaluating fadraciclib in
patients with acute myeloid leukaemia (AML) and myelodysplastic
syndromes (MDS), we are executing a precision medicine strategy to
evaluate fadraciclib in patients with solid tumors, with study
enrollment expected to begin by Q1 2021.”
“These exciting new findings revealing
fadraciclib’s chemical structure and describing its relevant
anti-cancer properties, reflect the highly productive collaboration
of ICR with Cyclacel to discover and develop innovative cancer
treatments,” said Professor Paul Workman, FMedSci, FRS, study
co-author and Chief Executive and President, The Institute of
Cancer Research, London, UK. “As a potent and selective inhibitor
of CDK2 and CDK9, we believe our cumulative findings to-date
support fadraciclib’s ability to address key cancer pathways in
solid tumors and leukaemias, indicating its potential as a new
targeted anti-cancer therapy.”
Cyclin-dependent kinases (CDKs) exist in many
isoforms and as key cell cycle regulators can play a critical role
in cancer growth. This preclinical characterization of fadraciclib
includes its potency and selectivity against CDK2 and CDK9 in vitro
and in a broad range of cancer cell lines including AML, breast and
colorectal. Further in vivo efficacy was demonstrated in leukemia
xenograft models.
Experimental results support fadraciclib’s
anti-cancer activity through CDK2/9 inhibition. In breast cancer
cell lines, short-pulse treatment with fadraciclib showed
preferential activity against transformed cells over normal cells.
This finding supports the compound’s potential benefit in cancers
addicted to cyclin E which can be rationally targeted by CDK2
inhibition. In AML models, fadraciclib was effective in inhibiting
CDK9 and suppressing the MCL1 protein to induce apoptosis or
programmed cell death of leukemia cells. Fadraciclib also
demonstrated synergy with BCL2 inhibitors such as venetoclax in AML
cells. In subcutaneous mouse xenograft models of AML and MLLr-AML,
nearly 100% tumor growth inhibition was achieved with oral
administration of fadraciclib at pharmacological doses.
Publication Details
Title: Fadraciclib (CYC065), a
novel CDK inhibitor, targets key pro-survival and oncogenic
pathways in cancerPublication Date: July 9,
2020URL:
https://doi.org/10.1371/journal.pone.0234103
About Cyclin-Dependent Kinases and
Fadraciclib
Cyclin-dependent kinases (CDKs) are critical for
cell cycle regulation and transcriptional elongation. Dysregulated
CDKs have been linked to the cancer hallmarks of uncontrolled
proliferation and increased survival. Fadraciclib (CYC065) is a
potent orally and intravenously available inhibitor of CDK2 and
CDK9. CDK9 regulates transcription of genes through phosphorylation
of RNA polymerase II (RNAP II) C-terminal domain (CTD). Inhibition
of CDK9 by fadraciclib suppresses CDK9-dependent gene expression
and reduces the level of MCL1, a key anti-apoptotic protein.
Fadraciclib is in an ongoing Phase 1,
first-in-human study in patients with advanced solid tumors. In
this all-comer study, target engagement and durable suppression of
the MCL1 biomarker were observed after a single dose of
fadraciclib. Tumor shrinkage and stable disease were observed in
five patients with cyclin E, MCL1 or MYC amplified advanced
cancers. In the ongoing part 2 of the study evaluating a more
intensive dosing regimen, a durable partial response has been
observed in a heavily pretreated patient with MCL1-amplified
endometrial cancer. Fadraciclib is also being evaluated in Phase 1
combination studies with venetoclax in relapsed or refractory CLL
and in relapsed or refractory AML or MDS. Preclinical data suggest
that fadraciclib may benefit patients with adult and pediatric
hematological malignancies such as CLL, AML, ALL, B-cell lymphomas,
multiple myeloma and certain cyclin E-addicted or MYC-amplified
solid tumors, including certain forms of breast cancer,
neuroblastoma, ovarian cancer and uterine serous carcinoma.
About Cyclacel Pharmaceuticals,
Inc.
Cyclacel Pharmaceuticals is a clinical-stage
biopharmaceutical company developing innovative cancer medicines
based on cell cycle, transcriptional regulation and DNA damage
response biology. The transcriptional regulation program is
evaluating fadraciclib as a single agent in solid tumors and in
combination with venetoclax in patients with relapsed or refractory
AML/MDS and CLL. The DNA damage response program is evaluating an
oral combination of sapacitabine and venetoclax in patients with
relapsed or refractory AML/MDS. An investigator-sponsored trial
(IST) is evaluating an oral combination of sapacitabine and
olaparib in patients with BRCA mutant breast cancer. The
anti-mitotic program is evaluating CYC140, a PLK1 inhibitor, in
advanced leukemias/MDS patients. 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.
Contacts
Company: |
Paul McBarron, (908) 517-7330, pmcbarron@cyclacel.com |
Investor Relations: |
Russo Partners LLC, Jan Medina, (646) 942-5632,
Jan.Medina@russopartnersllc.com |
© Copyright 2020 Cyclacel Pharmaceuticals, Inc.
All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks
of Cyclacel Pharmaceuticals, Inc.
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