AEterna Zentaris Presents Two Posters on its PI3K Inhibitor Compound, AEZS-126, at AACR Annual Meeting
April 21 2009 - 10:00AM
PR Newswire (US)
In Vitro and In Vivo Data Show AEZS-126 as Promising Oral Compound
for Future Clinical Development in Cancer QUEBEC CITY, April 21
/PRNewswire-FirstCall/ -- AEterna Zentaris Inc. (TSX: AEZ; NASDAQ:
AEZS), a global biopharmaceutical company focused on endocrine
therapy and oncology, today presented two posters on AEZS-126, a
promising compound for clinical intervention of the PI3K/ Akt
pathway in human tumors. The posters were presented at the American
Association for Cancer Research (AACR) Annual Meeting in Denver,
Colorado. Poster #3705 Entitled, "AEZS-126, a new orally
bioavailable PI3K inhibitor with antitumor effects", I. Seipelt, S.
Baasner, M. Gerlach, M. Teifel, J. Fensterle, L. Blumenstein, G.
Mueller and E. Guenther, the poster focuses on ADMET and safety
profiling of the compound, as well as in vivo pharmacokinetic
experiments and mouse xenograft antitumor studies. Results AEZS-126
was identified as a potent inhibitor of class I PI3Ks in
biochemical and cellular assays and demonstrated favorable
properties in early in vitro ADMET screening including microsomal
stability, plasma stability and screening against a large safety
profile composed of receptors, enzymes and cardiac ion-channels.
During the course of in vivo pharmacokinetic experiments and mouse
xenograft antitumor studies, the oral bioavailability in mice was
determined to be about 60%, leading to micromolar plasma levels
which are well above the nanomolar IC50 values in in vitro studies.
Significant antitumor activity was observed at 30mg/kg daily oral
administration in Hct116 and A549 models. Conclusion These data
suggest that AEZS-126 is a promising compound for clinical
intervention of the PI3K/Akt pathway in human tumors. Poster #3706
Entitled, "In vitro profiling of the potent and selective PI3K
inhibitor, AEZS-126", I. Seipelt, M. Gerlach, L. Blumenstein, G.
Mueller, M.Teifel, E. Polymeropoulos and E. Guenther, the poster
outlines the key in vitro characteristics of this compound that led
to its selection for in vivo development. Results AEterna Zentaris
has identified a new generation of low molecular weight
pyridopyrazine compounds as highly potent and selective inhibitors
of class I PI3Ks. Presented here, are the key in vitro
characteristics of AEZS-126 that led to its selection for in vivo
development. AEZS-126 inhibits PI3Ka with an IC50 value of 10nM and
proved to be a potent inhibitor of Akt phosphorylation in cellular
assays. Mode-of-action studies showed that AEZS-126 acts as an ATP
competitive compound. The in vitro antiproliferative activity
against different human tumor cell lines (MDA-MB 468, U87, Hct116,
PC-3, A549 and others) was determined, with EC50 values in the
nanomolar range. Conclusion The optimization of AEterna Zentaris'
pyridopyrazine lead structure regarding kinase selectivity,
cellular potency and ADMET properties, led to the identification of
AEZS-126, a compound which has a favorable in vitro pharmacologic
profile for further in vivo profiling. About AEterna Zentaris Inc.
AEterna Zentaris Inc. is a global biopharmaceutical company focused
on endocrine therapy and oncology, with proven expertise in drug
discovery, development and commercialization. News releases and
additional information are available at http://www.aezsinc.com/.
Forward-Looking Statements 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
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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
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DATASOURCE: AETERNA ZENTARIS INC. CONTACT: Investor Relations:
Ginette Vallieres, Investor Relations Coordinator, (418) 652-8525
ext. 265, ; Media Relations: Paul Burroughs, Director of
Communications, (418) 652-8525 ext. 406,
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