Combination Potential of Cyclacel's Sapacitabine and Seliciclib Reported at AACR

Combination Potential of Cyclacel's Sapacitabine and Seliciclib Reported at

Sequential Treatment Showed Antitumor Activity in Patients With Incurable
BRCA-Deficient Cancers

BERKELEY HEIGHTS, N.J., April 9, 2013 (GLOBE NEWSWIRE) -- Cyclacel
Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the
"Company") today announced updated data from an open label, single arm, Phase
1 escalation trial of the Company's two product candidates, sapacitabine, a
nucleoside analogue, and seliciclib, a cyclin-dependent kinase (CDK)
inhibitor, as an orally-administered sequential treatment regimen in
heavily-pretreated patients with advanced solid tumors. Data were presented as
an oral presentation during the 104^th Annual Meeting of the American
Association of Cancer Research (AACR) 2013 in Washington, D.C.

"We are encouraged by the responses seen with the sequential administration of
sapacitabine and seliciclib in patients who carry a BRCA mutation," said
Geoffrey Shapiro, M.D., Director, Early Drug Development Center, Dana-Farber
Cancer Institute and Associate Professor, Department of Medicine, Harvard
Medical School. "Our findings have shown that some patients who carried a BRCA
mutation achieved durable partial responses and prolonged stable disease by
this treatment regimen."

"The promising findings of Dr. Shapiro's work on the Phase 1 study show that
sequential treatment with sapacitabine and seliciclib is tolerable and
active," said Judy Chiao, M.D., Vice President Clinical Development and
Regulatory Affairs of Cyclacel. "This clinical observation may be directly
related to the drugs' mechanism of action acting on the ability of cancer
cells to undergo DNA repair through the homologous recombination or HR
pathway. If these preliminary findings are confirmed by further work, these
drugs may provide an important treatment alternative for patients with
BRCA-deficient cancers."

Based on these emerging results, the investigators continue to enroll an
enriched population of patients who carried a BRCA mutation in the trial, in
whom the combination has been most efficacious. Additional schedules of the
combination therapy are under evaluation. BRCA mutation carrier status and
homologous recombination defect (HRD) status may be potential biomarkers for
response to this combination across multiple tumor types.


To date, 38 patients with incurable solid tumors and adequate organ function
have been enrolled in the Phase 1 study, 16 of them found to be BRCA mutation
carriers. Sapacitabine was administered twice daily for seven days followed
by seliciclib twice daily for three days. Four patients with BRCA-deficient
pancreatic, breast or ovarian cancers had confirmed partial responses to the
drug combination. Based on available follow-up to date, three patients are
experiencing durable partial responses, with the longest lasting more than 78
weeks.Researchers observed stable disease of 12 weeks or more in eight
additional patients, including two patients with ovarian and breast cancers
who carried BRCA mutations and whose stable disease lasted 64 weeks and 21
weeks, respectively. The maximum tolerated doses were 50 mg sapacitabine
twice daily and 1,200 mg seliciclib twice daily. Dose-limiting toxicities
included reversible transaminase elevations and neutropenia. Adverse events
were mild to moderate in intensity. Results of skin biopsies after treatment
showed a 2.3-fold increase in DNA damage induced by sapacitabine, as measured
by gamma-H2AX immunohistochemistry. Additional DNA damage occurred after
treatment with seliciclib with a 0.58-fold further increase in gamma-H2AX

About sapacitabine

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 650 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.
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. 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. In a Phase 1 study, sapacitabine, in combination
with Cyclacel's seliciclib, showed antitumor activity in cancer patients found
to be carriers of BRCA mutations. 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 seliciclib

Seliciclib is an orally-available CDK inhibitor molecule that selectively
inhibits multiple enzyme targets, CDK2, CDK7 and CDK9, which are central to
the process of cell division and cell cycle control. Seliciclib treatment has
been reported to inhibit the two major DNA double-strand break (DSB) repair
pathways, homologous recombination (HR) and non-homologous end joining (NHEJ),
by reducing expression of components of each pathway. Seliciclib has been
evaluated to date in approximately 380 patients and is currently in randomized
Phase 2 trials in patients with previously treated lung cancer and
nasopharyngeal cancer.

About 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 for additional

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 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.
         Corey Sohmer
         (908) 517-7330

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