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Aeterna Zentaris Presents Proof-of-Concept For Disorazol Z Cytotoxic Conjugates, Such As AEZS-125, In Ovarian Cancer Mouse Model At ENA Symposium

QUÉBEC CITY, CANADA, Nov. 8, 2012 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") today presented encouraging preclinical results for disorazol Z cytotoxic conjugates, such as AEZS-125, in ovarian cancer. Results showed the compound's high potential for the treatment of luteinizing hormone-releasing hormone (LHRH) receptor positive tumors. Data were presented by the Company's Director of Preclinical Development, Babette Aicher, PhD, during a poster presentation at the 24 th EORTC-NCI-AACR (ENA) Symposium on "Molecular Targets and Cancer Therapeutics", currently held in Dublin, Ireland. The study is funded through a grant from the German Ministry of Education and Research.

Juergen Engel, PhD, Aeterna Zentaris President and CEO stated, "Disorazol Z cytotoxic conjugates such as AEZS-125, are an extension of our AEZS-108 innovative LHRH receptor targeted platform in oncology. These encouraging results presented at the ENA Symposium will enable us to select a specific drug candidate for further preclinical development expected to start in the first quarter of 2013."

Conclusions

  • All conjugates of D-Lys 6 -LHRH and disorazol Z analyzed, demonstrated high potential regarding the treatment of LHRH-receptor positive tumors;
  • For all conjugates, including AEZS-125, proof-of-concept could be demonstrated in an LHRH-receptor positive A2780 ovarian cancer xenograft model;
  • Experiments are currently under way addressing:
    • Correlation of tumor LHRH-receptor expression and treatment efficacy;
    • Evaluation of additional tumor models, such as endometrium and triple-negative breast cancer;
    • Assessment of early safety parameters and orientating acute toxicity in rodent models.

The poster, " Highly Potent Cytotoxic Conjugates of Disorazol Z Linked to a LHRH-Receptor Targeting Peptide such as AEZS-125, Interfere with Cell Cycle Progression in Human Cancer Cell Lines and Suppress Tumor Growth in a LHRH-Receptor Positive Ovarian Cancer Xenograft Model", B. Aicher, T. Schuster, L. Blumenstein, P. Schmidt, H. Irschik, R. Jansen, R. Mueller, E. Guenther, M. Teifel, can be viewed through this link .

About Disorazol Z Cytotoxic Conjugates such as AEZS-125

AEZS-125 is a disorazol Z (AEZS-137) cytotoxic conjugate linked to a Luteinizing Hormone-Releasing Hormone (LHRH)-receptor targeting peptide. Disorazol Z is a novel natural compound isolated from myxobacterium Sorangium cellulosum with outstanding cytotoxic activity. Disorazol Z is a macrocyclic polyketide which is available via fermentation in high yield and purity. Besides tubulin binding, disorazol Z has pro-apoptotic properties and arrested cancer cells in G2 stage of the cell cycle at subnanomolar concentrations. Disorazol Z is an ideal partner for the formation of cytotoxic conjugates with peptides and proteins to selectively target cancer cells.

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