ASM; USOTC:ATSMY) announces that its scientists and
collaborators are
presenting six posters on AS1413 (amonafide L-malate) and AS1411 this
week at
the annual meeting of the American Association for Cancer
Research in
Washington, DC. The presentations highlight the distinctive features
and
potential of these two novel cancer drugs, both of which are in
advanced
clinical testing.
Glyn Edwards, CEO of Antisoma, said: "AS1413 and AS1411 are both un-
partnered
products with significant commercial potential. The latest data on
AS1413
reinforce the clear differentiation of this drug from current
leukaemia
treatments and its potential to offer unique benefits to patients."
AS1413 interferes with the replication of DNA prior to cancer cell
division. The
drug does this by preventing the enzyme Topoisomerase II (TopoII) from
binding
to DNA. One presentation shows how this action differs from that of
classical
TopoII inhibitors, a widely used class of cancer therapeutics. It
demonstrates
that AS1413 retains activity in leukaemia cells resistant to classical
TopoII
inhibitors. Antisoma is conducting a phase III trial of AS1413 in patients
with
secondary acute myeloid leukaemia (secondary AML), a disease where
drug
resistance is common. The trial compares AS1413-based treatment with
standard
current treatment based on the classical TopoII inhibitor daunorubicin.
A presentation on AS1411 demonstrates anti-tumour effects in a rat
xenograft
model of colorectal cancer. This adds to previous data from lung and
renal
cancer xenografts and data from cell lines representing many types of
cancer.
The findings are consistent with broad potential of AS1411 across
solid and
blood cancers.
Effects of AS1411 in an AML cell line are described in a further
presentation.
AS1411 killed leukaemia cells, and a combination of AS1411 with
cytarabine
produced synergistic (more than additive) anti-cancer effects. This
drug
combination is being evaluated in an ongoing phase IIb trial in patients
with
AML. Other experiments demonstrated synergistic effects of combinations
between
AS1411 and two of the newer approved products for treatment of blood
cancers,
decitabine and clofarabine.
Three posters from collaborators provide new data on the mechanisms by
which
AS1411 exerts its anti-cancer effects. Further details of all the
presentations
are provided below and on the AACR website at www.aacr.org.
Enquiries:
Glyn Edwards, CEO
Daniel Elger, VP, Marketing & Communications +44 (0)7909 915 068
Antisoma plc
Mark Court/Lisa Baderoon/Catherine Breen +44 (0)20 7466 5000
Buchanan Communications
Seth Lewis +1 646 378 2923
The Trout Group
Except for the historical information presented, certain matters discussed
in
this statement are forward looking statements that are subject to a number
of
risks and uncertainties that could cause actual results to differ
materially
from results, performance or achievements expressed or implied by such
statements. These risks and uncertainties may be associated with product
discovery and development, including statements regarding the company's
clinical
development programmes, the expected timing of clinical trials and
regulatory
filings. Such statements are based on management's current expectations,
but
actual results may differ materially.
Details of the AACR presentations
AS1413
* #3665 The novel DNA intercalator amonafide (AS1413) disrupts the cell
cycle
by mechanisms distinct from topo II inhibitors daunorubicin and
etoposide
(Senderovich et al.) Tuesday, 20 Apr 2010, 9am-12pm; Exhibit Hall A-C,
Poster Section 27
AS1411
* #3647 Gene expression analysis in AML cell line MV4-11 following
treatment
with the anti-cancer aptamer AS1411 (Senderovich et al.) Tuesday 20 Apr
2010, 9am-12pm; Exhibit Hall A-C, Poster Section 27
* #2614 Anti-tumor efficacy and pharmacokinetics of the novel aptamer
AS1411
in a continuous infusion nude rat xenograft model (Green et al.) Monday
19
Apr 2010, 2-5pm; Exhibit Hall A-C, Poster Section 25
* #4450 A new paradigm for AS1411 activity: Uptake by macropinocytosis
and
induction of macropinocytosis by a nucleolin-dependent mechanism
(Reyes-Reyes et al.) Tuesday 20 Apr 2010, 2-5pm; Exhibit Hall A-C,
Poster
Section 23
* #4455 Differential response to AS1411 in a pair of VHL-positive and
VHL-negative renal carcinoma cell lines (Islam et al.) Tuesday 20 Apr
2010, 2-5pm; Exhibit Hall A-C, Poster Section 23
* #3642: AS1411 causes a specific increase in levels of cell surface
nucleolin
in responsive cell lines (Teng et al.) Tuesday 20 Apr 2010, 9am-12pm;
Exhibit Hall A-C, Poster Section 27
A number of abstracts relating to ASA404 are also being presented at the
meeting. Abstracts for all the presentations and details of their
timings/location are available at www.aacr.org
About AS1413
AS1413 (amonafide L-malate) is a DNA intercalator that induces
apoptotic
signalling by blocking Topoisomerase II binding to DNA. This differs
from the
action of classical Topoisomerase II inhibitors, which
induce apoptosis by
causing extensive DNA damage. A further distinctive feature of AS1413
is its
ability to evade Pgp and related transporters responsible for
multi-drug
resistance (MDR). Patients with secondary AML often have multi-drug
resistant
disease. In an 88-patient phase II trial, the combination of
AS1413 and
cytarabine produced a 38.6% CR rate in patients with secondary AML. The
same
regimen is being compared with daunorubicin plus cytarabine in a
pivotal
randomised phase III trial, ACCEDE, which is expected to report data in
late
2010 or early 2011.
About AS1411
AS1411 is a DNA aptamer. Aptamers are short pieces of DNA or RNA that
assume a
specific three-dimensional shape capable of highly specific targeting.
AS1411
binds to nucleolin, a protein expressed in the nucleus of all cells but
which in
cancer cells is also found on the cell surface. When AS1411 binds to
nucleolin
on cancer cells, it is internalised and causes apoptosis through
interference
with various functions of nucleolin. AS1411 was originally developed by Dr
Paula
Bates, Dr John Trent and Prof. Donald Miller at the University of Alabama
and
then at the University of Louisville. Antisoma added AS1411 to its pipeline
when
it acquired the Louisville-based company Aptamera Inc. in February 2005.
Data
from a randomised phase II trial combining AS1411 with cytarabine in
patients
with AML have provided evidence of activity, and a phase IIb trial is now
ongoing in the same setting.
About Antisoma
Antisoma is a London Stock Exchange-listed biopharmaceutical company
that
develops novel products for the treatment of cancer. The Company has
operations
in the UK and the US. Please visit www.antisoma.com for further
information about Antisoma.
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