APTO-253 In Vivo Data Demonstrate Single-Agent and
Combination Activity in AML
SAN FRANCISCO, CA, Dec. 9, 2014 /PRNewswire/ - 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.
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