Aeterna Zentaris presents AEZS-131 data against cancer at AACR meeting

Apr 6 2011

Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") today announced that a poster on its highly selective Erk 1/2 inhibitor anticancer compound, AEZS-131, was presented at the 102^nd annual meeting of the American Association for Cancer Research currently held at the Orange County Convention Center in Orlando, Florida.

Poster #3563

Entitled, "A highly selective Erk 1/2 inhibitor with in-vivo anti tumor potency", Irene Seipelt, Eckhard Guenther, Lars Blumenstein, Gilbert Mueller, Peter Schmidt, Babette Aicher, Michael Teifel and Matthias Gerlach (Aeterna Zentaris GmbH).

Results

AEZS-131 is an orally active small molecular compound that selectively inhibits Erk 1/2 with an IC50 of 4nM, blocks cellular Rsk-1 phosphorylation, modulates downstream cellular substrate activation, arrests tumor cells in G1 and inhibits the growth of multiple human tumor cell lines in the nanomolar range. In in vivo pharmacokinetic studies, AEZS-131 showed a favorable PK profile. Anti-tumor activity was studied in in vivo mouse xenograft experiments utilizing the HCT-116 colon cancer model. AEZS-131 significantly inhibited tumor growth and was well tolerated at daily doses up to 120 mg/kg.

Conclusion

Focus on inhibition of downstream kinase Erk 1/2 activity as a therapeutic target may be attractive because the pharmacologic inhibition of Erk 1/2 reverses Ras and Raf activation in cells which also demonstrate resistance to common Raf inhibitors, such as PLX-4720/4032.

"Inhibition of Erk represents a novel approach of targeting the Raf-Mek-Erk pathway which is frequently upregulated in cancer. AEZS-131 is a first-in-class Erk 1/2 inhibitor demonstrating proof-of-concept in vivo after oral administration." stated Juergen Engel, President and Chief Executive Officer of Aeterna Zentaris. "The activity in cells resistant to Raf inhibitors further underlines the potential of this approach in patients that are refractory to current treatment regimens."