APTO-253 In Vivo Data Demonstrate Single-Agent and Combination Activity in AML
SAN FRANCISCO, CA, Dec. 9, 2014 /CNW/ - Aptose Biosciences Inc. (Aptose)
(NASDAQ: APTO; TSX:APS), a clinical-stage company developing targeted
agents and molecular diagnostics to treat the underlying mechanisms of
cancer, today announced that preclinical data from its lead
investigational anticancer therapeutic APTO-253 were presented at the
56th American Society of Hematology (ASH) Annual Meeting and Exposition
in San Francisco.
On Monday, December 8th, 2014, Aptose presented the poster entitled: APTO-253 Induces KLF4 to Promote Potent in Vitro Pro-Apoptotic Activity
in Hematologic Cancer Cell Lines and Antitumor Efficacy as a Single
Agent and in Combination with Azacitidine in Animal Models of Acute
Myelogenous Leukemia. In the poster, Aptose researchers reported the first set of in vivo murine xenograft study data for APTO-253 in hematologic malignancies,
demonstrating antitumor activity as a single agent, and in combination
with the hypomethylating agent, azacitadine. Notably, combination
therapy led to enhanced antitumor activity versus either agent alone.
Furthermore, single agent and combination studies exhibited a favorable
safety profile with no evidence of bone marrow suppression.
The AML xenograft studies assessed various dose regimens of APTO-253,
including twice-weekly intravenous administration. As a single agent,
APTO-253 led to tumor growth inhibition or tumor regression in mice
bearing tumors of Kasumi-1, KG-1, THP-1 or HL-60 AML cells.
Furthermore, both once-weekly and twice-weekly dosing of APTO-253 in
combination with azacitidine resulted in enhanced antitumor activity
relative to either single agent alone in THP-1 and HL-60 AML models.
APTO-253 was effective and well tolerated as a single agent or in
combination with azacitidine in multiple AML xenograft models, had no
overt toxicity based on clinical observations and body weight
measurements, and did not cause bone marrow suppression.
"It's an exciting time to be advancing a first-in-class targeted
anticancer therapeutic in AML and other hematologic cancers," said
William G. Rice, Ph.D., Chairman, President and Chief Executive
Officer. "These results demonstrate that APTO-253 has potent
single-agent activity and presents an opportunity for combination
therapy with an effective hypomethylating agent, and potentially other
agents. Our findings also highlight the absence of myelosuppression,
which differentiates the APTO-253 program in the AML space. The
antitumor activity and safety profile strongly support our clinical
development plans for APTO-253."
Aptose also presented updated in vitro data supporting the biomarker strategy for patient identification. The
sensitivity of AML cell lines to APTO-253 correlated with higher
CDX2/KLF4 ratios, and separately correlated with the magnitude of KLF4
induction upon treatment with APTO-253.
Scientific literature report that bone marrow stem and progenitor cells
from approximately 90 percent of AML patients aberrantly express the
embryonic CDX2 gene, resulting in down-regulation of the innate tumor
suppressor gene Krüppel-like factor 4 (KLF4) and contributing to
development of leukemia. APTO-253 is the only clinical-stage agent
under development that acts through induction of the KLF4 gene.
APTO-253 is currently under evaluation in an ongoing open-label,
single-agent, dose-escalating Phase 1b clinical trial in patients with
relapsed or refractory hematologic malignancies, including AML and
high-risk MDS. Earlier this year, Aptose researchers reported the
ability of APTO-253 to induce cell death, or apoptosis, in multiple
blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved therapies for AML
or myelodysplastic syndromes (MDS), including cytarabine, daunorubicin,
azacitadine and decitabine. In a prior single-agent, Phase 1 clinical
study, APTO-253 demonstrated antitumor activity and a robust safety
profile in patients with solid tumors.
About Aptose
Aptose Biosciences is a clinical-stage biotechnology company committed
to discovering and developing personalized therapies addressing unmet
medical needs in oncology. Aptose is advancing new therapeutics focused
on novel cellular targets on the leading edge of cancer research,
coupled with companion diagnostics to identify the optimal patient
population for our products. Aptose's small molecule cancer
therapeutics pipeline includes products designed to provide enhanced
efficacy with existing anti-cancer therapies and regimens without
overlapping toxicities. Aptose Biosciences Inc. is listed on NASDAQ
under the symbol APTO and on the TSX under the symbol APS.
This press release contains forward-looking statements within the
meaning of Canadian and U.S. securities laws. Such statements include,
but are not limited to, statements relating to Aptose's plans,
objectives, expectations and intentions and other statements including
words such as "continue", "expect", "intend", "will", "should",
"would", "may", and other similar expressions and including, without
limitation, statements regarding clinical development. Such statements
reflect our current views with respect to future events and are subject
to risks and uncertainties and are necessarily based upon a number of
estimates and assumptions that, while considered reasonable by us are
inherently subject to significant business, economic, competitive,
political and social uncertainties and contingencies. Many factors
could cause our actual results, performance or achievements to be
materially different from any future results, performance or
achievements described in this press release. Such expressed or implied
factors include, among others: changes in our stock price; our ability
to meet listing requirements; our ability to obtain the capital
required for research and operations; the inherent risks in early stage
drug development including demonstrating efficacy; development
time/cost and the regulatory approval process; the progress of our
clinical trials; our ability to find and enter into agreements with
potential partners; our ability to attract and retain key personnel;
changing market conditions; stock market volatility; and other risks
detailed from time-to-time in our ongoing quarterly filings, annual
information forms, annual reports and annual filings with Canadian
securities regulators and the United States Securities and Exchange
Commission.
Should one or more of these risks or uncertainties materialize, or
should the assumptions set out in the section entitled "Risk Factors"
in our filings with Canadian securities regulators and the United
States Securities and Exchange Commission underlying those
forward-looking statements prove incorrect, actual results may vary
materially from those described herein. These forward-looking
statements are made as of the date of this press release and we do not
intend, and do not assume any obligation, to update these
forward-looking statements, except as required by law. We cannot assure
you that such statements will prove to be accurate as actual results
and future events could differ materially from those anticipated in
such statements. Investors are cautioned that forward-looking
statements are not guarantees of future performance and accordingly
investors are cautioned not to put undue reliance on forward-looking
statements due to the inherent uncertainty therein
SOURCE Aptose Biosciences Inc.
PDF available at: http://stream1.newswire.ca/media/2014/12/09/20141209_C9102_DOC_EN_43295.pdf
