Cyclacel's Sapacitabine Reported to Have Anti-Tumor Activity Against Ovarian
75% of Ovarian Cancer Patient Samples Highly Sensitive to Sapacitabine
Including Those Resistant to Therapy
BERKELEY HEIGHTS, N.J., Sept. 19, 2013 (GLOBE NEWSWIRE) -- Cyclacel
Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the
"Company") today announced updated data showing that sapacitabine has activity
against a majority of ovarian cancer samples taken from patients, including
resistant tumors. The data were reported at a poster presentation during the
American Association of Cancer Research (AACR) conference "Advances in Ovarian
Cancer: from concept to clinic" being held September 18-21, 2013, in Miami,
"We are encouraged by the activity signal of sapacitabine in ovarian cancer
samples," said Judy Chiao, M.D., Vice President, Clinical Development and
Regulatory Affairs of Cyclacel. "This observation may be directly related to
the drug's mechanism which is enhanced in cancer cells with reduced capacity
for DNA repair through the homologous recombination repair or HR pathway. In
addition to our ongoing Phase 3 registration trial of sapacitabine in acute
myeloid leukemia and Phase 2 studies in myelodysplastic syndromes, we are
continuing to evaluate sapacitabine as a potential treatment for patients with
solid tumors, and in particular those with BRCA-deficient cancers."
Cyclacel collaborators from the Northern Institute for Cancer Research,
Newcastle University, UK led by Nicola Curtin, Professor of Experimental
Therapeutics and Richard Edmondson, Professor of Gynaecological Oncology
reported that CNDAC, the active metabolite of sapacitabine, was active against
75% (30 of 40) of primary ovarian cancer (POC) samples isolated from patients.
In contrast cisplatin was active in less than half of the samples. Over half
of the cisplatin-resistant samples were sensitive to CNDAC, indicating that
sapacitabine has potential utility for treatment of ovarian cancers, including
platinum-resistant disease. The majority, but not all, of the samples tested
were from high grade serous ovarian cancers.
The HR activity of the ovarian samples was determined as HR deficient or HR
proficient by a functional assay. Sensitivity to sapacitabine was
substantially greater in HR deficient than HR proficient samples (mean GI
values of 135 nM versus 477 nM, respectively). This difference suggests that
HR status, or other surrogate markers such as BRCA mutation status, could be
used to enrich for potential responders in stratified clinical trials of
sapacitabine in patients with solid tumors.
Sapacitabine activity has been shown to be substantially enhanced in
celllineswithdefects or mutations in the HR pathway,including mutations in
ATM,BRCA1,BRCA2, RAD51 andXRCC3.The reported data further support the
potential for sapacitabine to be used as a treatment for HR defective cancers,
such as ATM- or BRCA-defective tumors. Clinical trials examining the activity
of sapacitabine in ATM-defective CLL, and of sapacitabine in combination with
Cyclacel's seliciclib in cancer patients with BRCA1 or BRCA2 mutations, are
currently in progress.
"Therapeutic potential of sapacitabine in ovarian cancers defective in
Poster Number: A33. Thursday September 19, 2013, 4:30 p.m. - 6:30 p.m.
Sapacitabine (CYC682), an orally-available nucleoside analogue, is being
studied in SEAMLESS, an ongoing, Phase 3, registration-directed trial in
elderly patients aged 70 years or older with newly diagnosed AML who are not
candidates for or have refused induction chemotherapy. Sapacitabine is in
Phase 2 trials in patients with hematological malignancies, including AML,
myelodysplastic syndromes (MDS), cutaneous T-cell lymphoma (CTCL), chronic
lymphocytic leukemia, small lymphocytic lymphoma, and also non-small cell lung
cancer (NSCLC), and a Phase 1 trial with seliciclib in patients with advanced
solid tumors. Sapacitabine acts through a novel DNA single-strand breaking
mechanism, leading to production of DNA double strand breaks (DSBs) and/or
checkpoint activation. Unrepaired DSBs cause cell death. Repair of
sapacitabine-induced DSBs is dependent on the homologous recombination (HR)
DNA repair pathway. Both sapacitabine and CNDAC, its major metabolite, have
demonstrated potent anti-tumor activity in preclinical studies.
Over 800 patients have received sapacitabine in clinical studies in patients
with AML, MDS, CTCL, NSCLC, hematological malignancies and solid tumors. At
the 2012 American Society of Hematology (ASH) Annual Meeting, data from the
pilot study and lead-in phase of SEAMLESS showed promising response rate,
overall survival and low 30-day and 60-day mortality in elderly patients with
AML aged 70 years or older receiving sapacitabine alternating with decitabine.
Results from a randomized Phase 2, single-agent study of sapacitabine,
including promising 1-year survival in elderly patients with AML aged 70 years
or older, were published in The Lancet Oncology in November 2012.
Data, presented at The Eighth Annual Hematologic Malignancies 2012 Conference,
from an ongoing, multicenter, Phase 2 randomized trial of single-agent oral
sapacitabine capsules in older patients with intermediate-2 or high-risk
myelodysplastic syndromes (MDS) after treatment failure of front-line
hypomethylating agents, such as azacitidine and/or decitabine, showed
sapacitabine nearly doubled expected median survival of elderly patients with
MDS after front-line therapy failure.
At the 2013 American Association of Cancer Research (AACR) Annual Meeting
data, from a Phase 1 study of sapacitabine in combination with Cyclacel's
seliciclib, which showed antitumor activity in cancer patients found to be
carriers of BRCA mutations was highlighted by the AACR's Annual Meeting
The FDA and the European Medicines Agency have designated sapacitabine as an
orphan drug for the treatment of both AML and MDS. Sapacitabine is part of
Cyclacel's pipeline of small molecule drugs designed to target and stop
uncontrolled cell division.
About Homologous Recombination Repair, BRCA Genes and Mutations
Breast cancer susceptibility proteins BRCA1 and BRCA2 are tumor suppressors
that ensure DNA stability and prevent uncontrolled cell growth in normal
cells. BRCA gene mutations are common in breast and ovarian cancer, but other
defects including suppression of BRCA1/2 expression by promoter
hypermethylation can produce HR defects in these and other tumors, including
NSCLC and AML.Although BRCA1/2 mutations are found in approximately 20% of
high grade serous ovarian cancers, around 50% are reported to be HR-defective
due to these and other modifications of HR components.
Genetic testing for BRCA status is routinely available and reimbursed by
payors. BRCA mutation has been linked to predisposition to breast and ovarian
cancer. According to the US National Cancer Institute, during her life time a
woman has a 60% chance of developing breast cancer and 15-40% chance of
developing ovarian cancer if she inherits a harmful BRCA mutation. These risks
are 5 times and over 10 times more likely respectively than for women without
the mutation. Risks are highest with a family history of multiple cases of
breast cancer; cases of both breast and ovarian cancer; one or more family
members with two primary cancers; Norwegian, Dutch, or Icelandic heritage; or
Ashkenazi (Central and Eastern European) Jewish background. Harmful BRCA1
mutations may additionally increase a woman's risk of developing
triple-negative breast, cervical, colon, pancreatic and uterine cancer.
Harmful BRCA2 mutations may increase a woman's risk of bile duct, gallbladder,
stomach, pancreatic cancer and melanoma. Men with harmful BRCA1 mutations have
an increased risk of male breast cancer and possibly pancreatic, early-onset
prostate, and testicular cancer. Harmful BRCA2 mutations may increase a man's
risk of developing male breast, pancreatic and prostate cancer.
About Cyclacel Pharmaceuticals, Inc.
Cyclacel is a biopharmaceutical company developing oral therapies that target
the various phases of cell cycle control for the treatment of cancer and other
serious diseases. Sapacitabine, Cyclacel's most advanced product candidate, is
the subject of SEAMLESS, a Phase 3 trial being conducted under an SPA with the
FDA as front-line treatment for acute myeloid leukemia (AML) in the elderly,
and other studies for myelodysplastic syndromes (MDS), chronic lymphocytic
leukemia (CLL) and solid tumors including breast, lung, ovarian and pancreatic
cancer. Cyclacel's strategy is to build a diversified biopharmaceutical
business focused in hematology and oncology based on a development pipeline of
novel drug candidates. Please visit www.cyclacel.com for additional
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 2013 Cyclacel Pharmaceuticals, Inc. All Rights Reserved. The
Cyclacel logo and Cyclacel® are trademarks of Cyclacel Pharmaceuticals, Inc.
CONTACT: Cyclacel Pharmaceuticals, Inc.
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