New In Vitro Data presented at AACR-NCI-EORTC International Conference on
Molecular Targets and Cancer Therapeutics in San Francisco
QUEBEC CITY, Oct. 25 /CNW Telbec/ - AEterna Zentaris Inc. (TSX: AEZ;
Nasdaq: AEZS), a global biopharmaceutical company focused on endocrine therapy
and oncology, today presented an abstract outlining novel data generated from
three AEZS-112 (formerly ZEN-012) follow-up multi-targeted cytotoxic
candidates at the AACR-NCI-EORTC International Conference on Molecular Targets
and Cancer Therapeutics being held this week at the Moscone Convention Center
in San Francisco, California. Following encouraging results, the Company will
pursue further research aimed at selecting an AEZS-112 follow-up candidate for
preclinical development in cancer.
David J. Mazzo, Ph.D., President and Chief Executive Officer at AEterna
Zentaris commented, "These encouraging new results for our AEZS-112 follow-up
compounds are further proof of the quality and depth of our internal drug
discovery engine, and we look forward to the continued development of these
compounds as potential novel oral cancer treatments."
The abstract #C218 entitled, "Highly Potent Cytotoxic Compounds with
Inhibitory Effects on Tubulin Polymerization and Topoisomerase II", reviewed
results of a pharmacological characterization of three follow-up compound
candidates to AEZS-112, AEterna Zentaris' multi-targeted cytotoxic compound
currently in a Phase 1 clinical trial for solid tumors and lymphoma. The
analysis was aimed at identifying compounds with either quantitative or
qualitative variations in either mode of action - inhibition of tubulin
polymerization, topoisomerase activity as well as antiangiogenic properties -
and/or tumor specificity for subsequent preclinical development.
AEZS-112 follow-up candidates were subjected to comprehensive in vitro
profiling with respect to mode of action, metabolic stability and interference
with clonogenic growth of human xenograft derived cell lines.
- All three AEZS-112 follow-up candidates were equal to or more efficient
in exerting cytotoxic activity in tumor cell lines and inhibiting
tubulin polymerization than AEZS-112, whereas induction of cell cycle
arrest and apoptosis was slightly improved;
- An interesting difference to the AEZS-112 profile is the inhibition of
topoisomerase I by compounds 2 and 3. Moreover, compound 2 displayed
significant higher potency for topoisomerase II inhibition than
- In vitro plasma and liver microsomal stability of the follow-up
candidates are comparable to AEZS-112, thus demonstrating suitability
for in vivo efficacy studies;
- Interference with clonogenic growth of xenograft-derived cells revealed
variability in the response of the different tumor classes to AEZS-112
and compound 1 treatment as a basis for selection of the most
appropriate in vivo efficacy models.
Based on their interesting in vitro profiles, all three follow-up
candidates will be subjected to human tumor xenograft in vivo models aimed at
selecting an AEZS-112 follow-up candidate for preclinical development.
The poster presentation is available in the Investor section of the
Company's website under "Events and Webcasts" at www.aeternazentaris.com.
AEZS-112 is a novel oral multi-targeted cytotoxic compound with
inhibitory effects on tubulin polymerization, topoisomerase II and
angiogenesis. In January 2007, the Company initiated a Phase 1 clinical trial
for solid tumors and lymphoma; primary endpoints will focus on determining the
safety and tolerability of the compound.
AEZS-112 has shown potent in vitro anti-proliferative activity at
nanomolar concentrations against human tumor cell lines of different origin.
The compound is active in tumor cell lines which are resistant to cisplatin
and doxorubicin as well as to tubulin inhibitors such as vincristine and
paclitaxel. Given orally once or twice weekly, AEZS-112 proved to be a potent
inhibitor of in vivo tumor growth in different models including mammary,
colon, skin, lung, renal and leukemic cancers.
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.
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