QUEBEC CITY, April 5 /PRNewswire/ - 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 102nd 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.”
About Erk 1/2 Inhibitor Compound
Extracellular signal-regulated kinases (“Erks”) act in the Ras-Raf-Mek-Erk signaling cascade and regulate various cellular processes such as cell growth, proliferation and survival in response to a variety of extracellular or intrinsically mutated upstream signals. Aeterna Zentaris has identified small molecular compounds that selectively inhibit Erk 1/2, among them AEZS-131, which has been shown to significantly inhibit tumor growth in in vivo studies. Early development of the Erk inhibitor AEZS-131 is an integral part of Aeterna Zentaris’ kinase research program comprising the investigation of different compounds for single Erk inhibition, single PI3K inhibition and dual Erk/PI3K kinase inhibition.
About Aeterna Zentaris Inc.
Aeterna Zentaris is a late-stage oncology drug development company currently investigating potential treatments for various cancers including colorectal, ovarian, endometrial cancer and multiple myeloma. The Company’s innovative approach of “personalized medicine” means tailoring treatments to a patient’s specific condition and to unmet medical needs. Aeterna Zentaris’ deep pipeline is drawn from its proprietary discovery unit providing the Company with constant and long-term access to state-of-the-art therapeutic options. For more information please visit www.aezsinc.com.
Forward-Looking Statements
This press release contains forward-looking statements made pursuant to the safe harbour provisions of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements involve known and unknown risks and uncertainties that could cause the Company’s actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of the Company to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. Investors should consult the Company’s quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to forward-looking statements. Investors are cautioned not to rely on these forward-looking statements. The Company does not undertake to update these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, unless required to do so by a governmental authority or by applicable law.
SOURCE AETERNA ZENTARIS INC.