Full Press Release Details
CYCLACEL PHARMACEUTICALS
ANNOUNCES COLLABORATION WITH THE UNIVERSITY OF EDINBURGH
TO STUDY ITS CDK INHIBITORS TO REDUCE RUNAWAY INFLAMMATION IN COVID-19 DISEASE
Fadraciclib and Seliciclib to Promote Apoptosis of
Inflammatory Neutrophils in the Setting of COVID-19 Lung Injury-
Heights, NJ and Dundee, UK, April 20, 2020 - 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.
assess Cyclacel's medicines above for their suitability for use in safety and experimental medicine 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.
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."
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."
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About COVID-19 Respiratory Distress & Cytokine Storm
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
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.
Copyright 2020 Cyclacel Pharmaceuticals,