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Aeterna Zentaris Presents Encouraging Updated Data On Its LHRH Receptor-Targeted Disorazol Z Cytotoxic Conjugates At AACR Meeting

QUÉBEC CITY, April 10, 2013 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") today presented encouraging updated proof-of-concept results for Disorazol Z cytotoxic conjugates, such as AEZS-125 and AEZS-138, in human ovarian and endometrial cancer xenograft models. Results further showed the compounds' high potential for the treatment of luteinizing hormone-releasing hormone ("LHRH") receptor positive tumors. Data were presented earlier today by Babette Aicher, PhD, the Company's Director of Preclinical Development, during a poster presentation at the American Association for Cancer Research ("AACR") annual meeting currently being held in Washington D.C. 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 and AEZS-138 are an extension of our AEZS-108 innovative LHRH-targeted platform in oncology. These results confirm the encouraging data presented at the ENA Symposium in November 2012, and will enable us to better select a specific drug candidate for further preclinical development expected to start during this quarter."

Conclusions

  • Conjugates of D-Lys 6-LHRH and Disorazol Z retained strong binding to the LHRH receptor and showed potent inhibition of tubulin polymerization. Cellular cytotoxicity of the conjugates was in the low nanomolar EC 50 range. Increased cytotoxicity in cells over-expressing the LHRH receptor, support receptor targeting as a mechanism of action;
  • AEZS-125 and AEZS-138 have been identified as the most promising candidates;
  • The LHRH receptor-dependent efficacies of Disorazol Z - D-Lys 6-LHRH conjugates in vitro and in mouse xenograft models that were presented, support the principle of tumor targeting by the LHRH receptor as already employed by the drug candidate AEZS-108, which is currently in a Phase 3 study in endometrial cancer and in Phase 2 studies in triple-negative breast cancer, bladder cancer and prostate cancer.

The poster, " LHRH receptor targeting as mechanism of anti-tumor activity for cytotoxic conjugates of Disorazol Z with the LHRH receptor agonistic peptide D-Lys 6-LHRH", B. Aicher et al. can be viewed through this link .

About Disorazol Z

Disorazol Z is a novel natural compound, with outstanding cytotoxic activity, isolated from the myxobacterium Sorangium cellulosum. Disorazol Z, a macrocyclic polyketide, is produced by a fermentation process providing high yield and purity. Besides tubulin binding, Disorazol Z has pro-apoptotic properties and has been shown to arrest cancer cells in G2M stage of the cell cycle at subnanomolar concentrations. Disorazol Z is an ideal partner for the formation of cytotoxic conjugates with peptides, proteins, and antibodies to selectively target cancer cells.

About Disorazol Z cytotoxic conjugates such as AEZS-125 and AEZS-138

AEZS-125 and AEZS-138 are novel cytotoxic conjugates based on the natural compound Disorazol Z and the LHRH receptor agonist D-Lys 6-LHRH. The peptide part directs the conjugates specifically to LHRH receptor expressing tumor cells, and mediates binding and uptake via endocytosis. Within the cancer cell, the conjugates are cleaved and Disorazol Z can deploy its potent anti-proliferative activity.

According to the literature, LHRH receptors occur in a number of human tumors, specifically in about 80% of ovarian and endometrial cancers. They are also expressed in prostate, urinary bladder and triple-negative breast cancer, while they are rarely found in normal tissues, except for the pituitary gland and reproductive organs. The LHRH receptor displays ideal properties for selective drug targeting.

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