QUEBEC CITY, April 5 /PRNewswire/ - Aeterna Zentaris Inc.
(NASDAQ: AEZS) (TSX: AEZ) (the "Company") today announced that
a poster on its highly selective Erk 1/2 inhibitor anticancer
compound, AEZS-131, was presented at the 102nd annual
meeting of the American Association for Cancer Research currently
held at the Orange County
Convention Center in Orlando,
Florida.
Poster #3563
Entitled, "A highly selective Erk 1/2 inhibitor with
in-vivo anti tumor potency", Irene Seipelt, Eckhard
Guenther, Lars Blumenstein,
Gilbert Mueller, Peter Schmidt, Babette
Aicher, Michael Teifel and
Matthias Gerlach (Aeterna Zentaris
GmbH).
Results
AEZS-131 is an orally active small molecular compound that
selectively inhibits Erk 1/2 with an IC50 of 4nM, blocks
cellular Rsk-1 phosphorylation, modulates downstream cellular
substrate activation, arrests tumor cells in G1 and inhibits the
growth of multiple human tumor cell lines in the nanomolar range.
In in vivo pharmacokinetic studies, AEZS-131 showed a
favorable PK profile. Anti-tumor activity was studied in in
vivo mouse xenograft experiments utilizing the HCT-116 colon
cancer model. AEZS-131 significantly inhibited tumor growth and was
well tolerated at daily doses up to 120 mg/kg.
Conclusion
Focus on inhibition of downstream kinase Erk 1/2 activity as a
therapeutic target may be attractive because the pharmacologic
inhibition of Erk 1/2 reverses Ras and Raf activation in cells
which also demonstrate resistance to common Raf inhibitors, such as
PLX-4720/4032.
"Inhibition of Erk represents a novel approach of targeting the
Raf-Mek-Erk pathway which is frequently upregulated in cancer.
AEZS-131 is a first-in-class Erk 1/2 inhibitor demonstrating
proof-of-concept in vivo after oral administration."
stated Juergen Engel, President and
Chief Executive Officer of Aeterna Zentaris. "The activity in cells
resistant to Raf inhibitors further underlines the potential of
this approach in patients that are refractory to current treatment
regimens."
About Erk 1/2 Inhibitor Compound
Extracellular signal-regulated kinases ("Erks") act in the
Ras-Raf-Mek-Erk signaling cascade and regulate various
cellular processes such as cell growth, proliferation and
survival in response to a variety of extracellular or
intrinsically mutated upstream signals. Aeterna Zentaris has
identified small molecular compounds that selectively inhibit
Erk 1/2, among them AEZS-131, which has been shown to
significantly inhibit tumor growth in in vivo studies. Early
development of the Erk inhibitor AEZS-131 is an integral part of
Aeterna Zentaris' kinase research program comprising the
investigation of different compounds for single Erk inhibition,
single PI3K inhibition and dual Erk/PI3K kinase
inhibition.
About Aeterna Zentaris Inc.
Aeterna Zentaris is a late-stage oncology drug development
company currently investigating potential treatments for various
cancers including colorectal, ovarian, endometrial cancer and
multiple myeloma. The Company's innovative approach of
"personalized medicine" means tailoring treatments to a patient's
specific condition and to unmet medical needs. Aeterna Zentaris'
deep pipeline is drawn from its proprietary discovery unit
providing the Company with constant and long-term access to
state-of-the-art therapeutic options. For more information please
visit www.aezsinc.com.
Forward-Looking Statements
This press release contains forward-looking statements made
pursuant to the safe harbour provisions of the U.S. Securities
Litigation Reform Act of 1995. Forward-looking statements involve
known and unknown risks and uncertainties that could cause the
Company's actual results to differ materially from those in the
forward-looking statements. Such risks and uncertainties include,
among others, the availability of funds and resources to pursue
R&D projects, the successful and timely completion of clinical
studies, the ability of the Company to take advantage of business
opportunities in the pharmaceutical industry, uncertainties related
to the regulatory process and general changes in economic
conditions. Investors should consult the Company's quarterly and
annual filings with the Canadian and U.S. securities commissions
for additional information on risks and uncertainties relating to
forward-looking statements. Investors are cautioned not to rely on
these forward-looking statements. The Company does not undertake to
update these forward-looking statements. We disclaim any obligation
to update any such factors or to publicly announce the result of
any revisions to any of the forward-looking statements contained
herein to reflect future results, events or developments, unless
required to do so by a governmental authority or by applicable
law.
SOURCE AETERNA ZENTARIS INC.