Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC, Nasdaq:CYCCP)
("Cyclacel" or the "Company"), a biopharmaceutical company
developing innovative medicines based on cancer biology, announced
treatment of the first patient in a Phase 1/2 study evaluating the
safety and effectiveness of oral sapacitabine, a nucleoside
analogue, in combination with oral venetoclax, a BCL2 inhibitor, in
patients with relapsed or refractory AML or MDS.
“Sapacitabine is an oral nucleoside analogue that
is active in AML and MDS that is relapsed or refractory to prior
therapy such as cytarabine or hypomethylating agents. Combining
sapacitabine with venetoclax may offer an effective, oral treatment
regimen for patients who have failed front-line therapy,” said
Spiro Rombotis, President and Chief Executive Officer of Cyclacel.
“We are excited to follow up on the hypothesis generating results
from our SEAMLESS study with a novel, orally-administered
combination of sapacitabine and venetoclax given concomitantly.
This study is the fourth protocol to open as part of our strategic
alliance with The University of Texas MD Anderson Cancer Center
with the objective of evaluating three Cyclacel drug candidates in
patients with hematological malignancies.”
The Phase 1/2 study (NCT01211457) is intended to
enroll up to 40 patients with relapsed or refractory AML or MDS
with the objective of determining the safety and efficacy of the
combination. Secondary objectives include duration of response, CR,
CRp, PR, or major HI, transfusion requirements, number of
hospitalized days and overall survival.
Preclinical Data on Combinations of
Sapacitabine and BCL2 Inhibitors in AMLOral sapacitabine
is metabolized to CNDAC which causes single stranded breaks in the
DNA of growing cells, resulting in double stranded breaks and
cancer cell death when DNA is not repaired. The combination effect
of CNDAC and the BCL2 inhibitor ABT-737 was studied in vitro in AML
cellular models. A synergistic increase in induction of apoptosis
of cancer cells was observed when MV4-11 AML cells were treated
simultaneously with CNDAC and the BCL2 inhibitor. Treatment with
cytarabine and BCL2 inhibitors resulted in similar synergy (Frame S
et al., 14th European Hematology Association Congress, 2009).
About Venetoclax in AMLThe FDA
granted accelerated approval of oral venetoclax tablets (ABT-199)
in combination with azacitidine or decitabine or low-dose
cytarabine for the treatment of newly-diagnosed AML in adults who
are aged 75 years or older or have comorbidities that preclude use
of intensive induction chemotherapy (Venetoclax Prescribing
Information PDF). The approval is based on two non-randomized,
open-label clinical studies (NCT02203773 and NCT02287233) in which
complete remission rates of 54%, 37%, and 21% were observed for
decitabine, azacitidine or low-dose cytarabine combinations with
venetoclax, respectively. Azacitidine, cytarabine and decitabine
are nucleoside analogues administered by intravenous or
subcutaneous injection. Continued approval for this indication may
be contingent upon verification and description of clinical benefit
in confirmatory trials.
About Sapacitabine Clinical Studies in
AML/MDSSapacitabine is active in relapsed or refractory
AML or MDS. In a Phase 1 dose escalation trial of single agent
sapacitabine 11 patients with relapsed or refractory AML or MDS
responded (4 CR, 2 CRp, 5 CRi). In a Phase 2 single agent study of
63 patients with MDS who had progressed or relapsed after
decitabine or azacitidine 9 patients responded (2 CR, 2 CRp, 5
major HI).
Sapacitabine as a single agent is active in
previously untreated AML. In a randomized Phase 2 study of
sapacitabine of 105 patients aged 70 years or older with untreated
or first relapse AML, 28 out of 86 previously untreated patients
responded (9 CR, 1 CRp, 3 CRi, 2 PR and 13 HI). In a Pilot/Lead-in
study of sapacitabine alternating with decitabine 46 newly
diagnosed AML patients aged 70 or older were administered the same
regimen as the experimental arm in SEAMLESS. Nineteen patients
responded (10 CR, 4 PR and 5 HI).
The randomized, open-label, Phase 3 SEAMLESS study
enrolled 482 patients, aged 70 or older, with newly diagnosed AML
who were not candidates for or refused intensive therapy. Patients
were stratified by peripheral baseline white blood cell count
(WBC), antecedent hematologic disease (AHD) and bone marrow blasts
and randomized 1:1 to receive either intravenous decitabine
administered in alternating cycles with oral sapacitabine or
intravenous decitabine alone. The primary endpoint of demonstrating
statistically significant improvement in overall survival (OS) was
not met. A higher CR rate, a secondary endpoint, was observed on
the decitabine-sapacitabine arm (17% versus 11%). Other endpoints
and safety were similar between the arms. Stratified subgroup
analyses showed that in a large subgroup of patients (n=319) with
low WBC a trend towards improved OS (HR=0.84 [0.66, 1.06], nominal
p=0.14) and a significantly higher CR rate (21% versus 9%, nominal
p=0.0017) were observed favoring decitabine-sapacitabine. The
opposite effect was observed in the high WBC subgroup.
About Cyclacel Pharmaceuticals,
Inc.Cyclacel Pharmaceuticals is a clinical-stage
biopharmaceutical company using cell cycle, transcriptional
regulation and DNA damage response biology to develop innovative
medicines based on cancer biology. Cyclacel's transcriptional
regulation program is evaluating CYC065, a CDK 2/9 inhibitor, in
relapsed, refractory CLL and AML patients. The recommended phase 2
dose of CYC065 has been determined in advanced solid tumors and an
oral formulation is ready for evaluation. The DNA damage response
program is evaluating a sequential regimen of sapacitabine and
seliciclib, a CDK inhibitor, in patients with BRCA positive,
advanced solid cancers. The anti-mitotic program is evaluating
CYC140, a PLK1 inhibitor in AML 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 StatementsThis
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 |
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Company: |
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Paul McBarron, (908) 517-7330, pmcbarron@cyclacel.com |
Investor Relations: |
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Russo partners LLC, Alexander Fudukidis, (646) 942-5632, |
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alex.fudukidis@russopartnersllc.com |
© Copyright 2019 Cyclacel Pharmaceuticals, Inc. All
Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks of
Cyclacel Pharmaceuticals, Inc.
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