AEterna Zentaris To Further Develop Three Follow-up Multi-Targeted Cytotoxic Candidates To AEZS-112 As Potential Novel Cancer Treatment

AEterna Zentaris Inc., a global biopharmaceutical company focused on endocrine therapy and oncology, recently 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."

Results

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.

Conclusions

• 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 AEZS-112;
• 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

About AEZS-112
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.

SOURCE: AEterna Zentaris Inc.