Aeterna Zentaris Presents a Poster on its Dual Inhibitors for PI3K and Erk, as well as an Oral Presentation Reporting Data on Selective Erk Inhibitors, at AACR Annual Meeting
In Vitro and In Vivo Data Show AEZS-126 as a Promising Oral Compound for Future Clinical Development in Cancer
QUEBEC CITY, April 20 /PRNewswire-FirstCall/ -- Aeterna Zentaris
Inc. (NASDAQ:AEZS) (NASDAQ:TSX:) (NASDAQ:AEZ) (the "Company"), a late-stage drug
development company specialized in oncology and endocrine therapy,
today presented a poster on dual Erk/PI3K inhibitors and made an
oral presentation on its selective Erk inhibitors, at the American
Association for Cancer Research (AACR) Annual Meeting in
Oral Presentation, Abstract #3856
Entitled, "A highly selective Erk-inhibitor with
antiproliferative efficacy and the potential for combination
therapy with modulators of the PI3K pathway", I. Seipelt, L.
Blumenstein, S. Baasner, G. Mueller, B. Aicher, M. Teifel, E.
Guenther, M. Gerlach, the presentation outlines data on selective
Erk inhibitors as antiproliferative agents either as monotherapy or
in combination with inhibitors of the PI3K/Akt pathway.
Aeterna Zentaris has identified small molecular compounds that
inhibit Erk in the low nanomolar range and show an excellent
selectivity profile. Other serine threonine, lipid or tyrosine
kinases are not inhibited at concentrations up to 10(micro)M.
Further studies revealed an ATP competitive mode of action and the
potent inhibition of the cellular downstream target Rsk1 in tumor
cells with an IC50 value of 158nM. The lead structure AEZS-131
produces cell cycle arrest in G1 and results in growth inhibition
of cancer cells. Furthermore, the potential of combination therapy
of AEZS-131 with inhibitors of the PI3K pathway was addressed and
synergistic anti-proliferative activity was observed e.g. with the
selective PI3K inhibitor, AEZS-126.
These results support further evaluation of selective Erk
inhibitors as antiproliferative agents either as monotherapy or in
combination with inhibitors of the PI3K/Akt pathway.
Entitled, "Dual inhibitors for PI3K and Erk induce growth
inhibition of tumor cells", I. Seipelt, M. Gerlach, S. Baasner, L.
Blumenstein, G. Mueller, B. Aicher, E. Guenther, M. Teifel, the
poster focuses on key characteristics of the compound class that
led to the selection of AEZS-132 for in vivo evaluation.
A multi-parameter optimization program for kinase inhibitor
selectivity, cellular efficacy, physicochemical and in vitro ADMET
properties has led to the discovery of a small molecular compound
class with an uniquely advantageous dual kinase inhibition profile.
These ATP competitive compounds inhibit Erk and PI3K in the
nanomolar range and exert high selectivity against other serine
threonine and tyrosine kinases. For the frontrunner compound,
AEZS-132, antitumor efficacy was demonstrated in several human
tumor cell lines including HCT116, A549, MDA-MB 468, and PC-3. In
in vivo antitumor studies, significant antitumor activity was
observed at 30 mg/kg daily oral administration of AEZS-132 in
HCT116 and Hec1B tumor xenografts, with T/C values of 0.33 (HCT116)
and 0.57 (Hec1B), respectively. Furthermore, target modulation has
been demonstrated in tumor samples.
The optimization of Aeterna Zentaris' pyridopyrazine compounds
towards dual inhibition of PI3K and Erk resulted in the
identification of AEZS-132, a unique dual inhibitor of PI3K and Erk
with a favourable pharmacology and ADMET profile for further
evaluation as an antitumor agent.
Juergen Engel, Ph.D., President and CEO of Aeterna Zentaris
stated, "These results not only demonstrate the potential of
Erk/PI3K inhibitor compounds as novel treatments in oncology, but
also position us as a leading player in this field beyond
perifosine, our Akt-inhibitor currently in Phase 3 trials for
multiple myeloma and colorectal cancer."
About Aeterna Zentaris Inc.
Aeterna Zentaris Inc. is a late-stage drug development company
specialized in oncology and endocrine therapy. News releases and
additional information are available at www.aezsinc.com.
This press release contains forward-looking statements made
pursuant to the safe harbor provisions of the U.S. Securities
Litigation Reform Act of 1995. Forward-looking statements involve
known and unknown risks and uncertainties, which 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
the 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
except if we are required by a governmental authority or applicable
Source: AETERNA ZENTARIS INC.
CONTACT: Investor Relations: Ginette Vallieres, Investor
Coordinator, (418) 652-8525 ext. 265, email@example.com; Media Relations:
Paul Burroughs, Director of Communications, (418) 652-8525 ext. 406,
Posted: April 2010