Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP;
"Cyclacel" or the "Company") a biopharmaceutical company developing
innovative medicines today announced that it entered into an
agreement with the University of Edinburgh to study fadraciclib
(CYC065) and seliciclib (CYC202 or R-roscovitine), its clinical
stage CDK2/9 inhibitors, as potential early treatments for the
inflammatory response observed in patients with COVID-19 disease.
The parties will assess Cyclacel’s medicines above for their
suitability for use in safety and efficacy studies in COVID-19
patients. This evaluation is part of a broader project
(“STOPCOVID”) studying the inflammatory pathways that lead directly
to COVID-19 lung injury, drawing upon more than 30 years of
experience from the University of Edinburgh’s Centre for
Inflammation Research. STOPCOVID is supported by a £2 million
(approximately $2.5 million) grant from LifeArc and the University
is seeking further funding.
“We are eager to evaluate the potential role of Cyclacel’s CDK
inhibitors as enablers of inflammatory neutrophil apoptosis,” said
Professor Kev Dhaliwal, STOPCOVID lead and Consultant in
Respiratory Medicine at The University of Edinburgh. “Clinical data
from international studies suggest that an early peripheral blood
neutrophil response is associated with a poor outcome in COVID-19.
If we can stop the inflammatory cascade early, we may be able to
prevent or delay the severity of COVID-19 induced inflammation and
the need for assisted ventilation in affected patients.”
Previously published research from The University of Edinburgh
and other investigators have found that CDK inhibitors, including
seliciclib, help resolve undesirable inflammation by promoting
apoptosis of inflammatory neutrophils. CDK inhibitors were shown to
reduce levels of the anti-apoptotic protein Mcl-1 and inhibit
transcription of interleukin-6 (IL-6), both of which are believed
to be drivers of the overactive systemic inflammatory response
severely damaging the lungs of symptomatic COVID-19 patients.
“Our published research showed that the CDK2/9 inhibitor
seliciclib, induced human neutrophil apoptosis possibly by
suppressing levels of the Mcl-1 anti-apoptotic protein and
augmented resolution of inflammation in 'neutrophil dominant'
models,” said Prof. Adriano G. Rossi, Chair of Respiratory and
Inflammation Pharmacology and Deputy Director of the Centre for
Inflammation Research. “We are interested in extending these
observations with fadraciclib, a second generation CDK inhibitor,
as part of our STOPCOVID project and possibly translating our
findings to benefit COVID-19 patients.”“We are excited to be
contributing fadraciclib and seliciclib to the global effort to
combat COVID-19,” said Spiro Rombotis, President and Chief
Executive Officer of Cyclacel. “As previously reported, our two
investigational CDK inhibitors suppress Mcl-1 in patients with
proliferative diseases. Seliciclib has also been shown to
efficiently suppress IL-6 transcription, a presumptive contributor
to COVID-19 cytokine storm. Seliciclib is active in models of lung
injury, pleurisy and rheumatoid arthritis and is undergoing
clinical investigation in patients with rheumatoid arthritis. We
are looking forward to working with The University of Edinburgh
team and are humbled by the possibility of helping COVID-19
patients in need.”
About COVID-19 Respiratory Distress &
Cytokine Storm
Most COVID-19 infected patients experience mild respiratory
problems. Some hospitalized patients require mechanical ventilation
because of severe hypoxia and acute lung injury which may lead to
rapid decline of respiratory function and death. This condition,
often called acute respiratory distress syndrome (ARDS), is thought
to be associated with a systemic inflammatory response of the
immune system (cytokine storm). Clinical correlates of mortality
from an analysis of 150 Chinese patients include old age, sepsis,
elevated d-dimer, and increased inflammatory parameters including
IL-6 and CRP (C-reactive protein).
About Anti-IL-6 Antibodies as Potential
Treatment for COVID-19
IL-6 is produced, along with other cytokines, by the immune
system in response to COVID-19 infection and contributes to
antiviral defense through the stimulation of a local and general
immune response. Once triggered continued synthesis of IL-6 has
pathological consequences through chronic inflammation. Evidence
points to an association of peak levels of IL-6 with the severity
of respiratory symptoms. Humanized anti-IL-6 receptor antibodies,
including tocilizumab and sarilumab, have been proposed as
potential treatments to attenuate the overactive immune response
and have begun evaluation in COVID-19 patients (NCT04317092 and
NCT04327388).
Published interim data from a small, uncontrolled Chinese study
suggest that IL-6 may be driving the inflammatory immune response
that causes ARDS in seriously ill COVID-19 patients. The study
showed that treatment with tocilizumab, a humanized anti IL-6
receptor antibody, in 15 of the 20 patients on study resulted in
reduced need for oxygen support and improved CRP levels.
About CDK Inhibitors as Potential Treatment for
COVID-19
The objective of treating COVID-19 patients with
transcriptionally-active cyclin-dependent kinase (CDK) inhibitors
is to dampen the overactive immune response in which activated
inflammatory neutrophils may contribute. Neutrophil survival is
promoted by Mcl-1 expression. Rossi et al showed that seliciclib
induced Mcl-1 downregulation and apoptosis of inflammatory
neutrophils in models of acute lung injury, arthritis and pleurisy.
Raje et al showed that seliciclib inhibited transcription and
secretion of IL-6 triggered by multiple myeloma cells adhering to
bone marrow stromal cells. Further it was shown that seliciclib was
more effective than anti-IL-6 antibody at suppressing Mcl-1
expression.
About the TRAFIC Clinical Study of Seliciclib in
Patients with Rheumatoid Arthritis
Seliciclib is being tested in patients with refractory
rheumatoid arthritis (RA) in an investigator-sponsored study
(‘TRAFIC’) led by Prof. J. Isaacs and colleagues at Newcastle
University and five other UK hospitals. TRAFIC is evaluating
seliciclib’s potential to help patients with RA by means of
reducing proliferation of synovial fibroblasts. As previously
reported the TRAFIC Independent Data Monitoring Committee
recommended that the study should continue to its second stage
which is currently enrolling.
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 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.
References
- Rossi AG, et al, Nature Med, 2006 Sept; 12(9): 1056-1064.
- Raje N, et al, Blood, 2005 Aug 1; 106(3): 1042–1047.
- Ruan Q, et al, Intensive Care Med, 2020
https://doi.org/10.1007/s00134-020-05991-x.
- Hou T, et al, JBC, 2007 282:37091-37102.
- Leitch AE, et al, Cell Death Differ, 2012 Dec;
19(12):1950-61.
- Lucas CD, et al, Mucosal Immunol, 2014 Jul; 7(4): 857–868.
- Dzhagalov I, et al, Blood, 2007 Feb 15; 109(4): 1620–1626.
Contacts
Company: |
Paul McBarron,
(908) 517-7330, pmcbarron@cyclacel.com |
Public Relations: |
Russo Partners LLC, Nic Johnson, (212) 845-4242,
Nic.Johnson@russopartnersllc.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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