QUÉBEC CITY, Aug. 30, 2011 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the “Company”) today announced that a poster on its novel orally active anticancer Erk inhibitor, which includes AEZS-131, was presented at the 242nd American Chemical Society National Meeting held at the Colorado Convention Center in Denver, Colorado. The poster was presented by Matthias Gerlach, Ph.D., Senior Director of Medicinal Chemistry for Aeterna Zentaris Inc.
Focus on inhibition of downstream kinase Erk 1/2 activity as a therapeutic target is attractive because the pharmacologic inhibition of Erk 1/2 reverses the activation of the Ras-Raf-Mek-Erk signal transduction pathway through many common deregulated molecular lesions in cancer. This pathway controls a number of fundamental cellular processes including cell survival, proliferation, motility and differentiation. It is constitutively activated in cancers of the lung, colon, pancreas, kidney, and ovary. Erk is pivotal in the pathway downstream of Ras, Raf and Mek, acting as central point where multiple signaling pathways coalesce to drive transcription.
Poster #17068
Entitled, “Novel Pyrido[2,3-b]pyrazines as orally active ERK inhibitors,” M. Gerlach, I. Seipelt, G. Mueller, T. Schuster, L. Blumenstein, B. Aicher, E. Guenther and M. Teifel.
Results
AEZS-131 is an orally active small molecular compound that selectively inhibits Erk 1/2 with an IC50 of 4nM. The in vitro antiproliferative efficacy proved to be excellent in diverse human tumor cell lines. GI50 values in the low nanomolar range were obtained. In vivo anti-tumor activity was studied in a mouse xenograft experiment utilizing the human HCT-116 colon cancer model. Up to 74% inhibition of tumor growth was achieved with daily oral doses of 30 - 120 mg/kg. Our medicinal chemistry programs are supported by X-ray crystallography and modeling towards the optimization of pyrido[2,3-b]pyrazines as novel series of kinase inhibitors.
Juergen Engel, Ph.D., Aeterna Zentaris’ President and Chief Executive Officer, commented: “As part of our targeting strategy in cancer with perifosine, AEZS-108, AEZS-112 and AEZS-120, we are proud to have identified the first in class Erk 1/2 inhibitor with in vivo anticancer activity. In parallel we are also developing AEZS-129 a pan PI3K inhibitor without m-TOR activity as well as AEZS-132, a dual inhibitor of PI3K and Erk.”
About Erk 1/2 Inhibitor Compounds
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 based on our knowledge with perifosine 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, multiple myeloma, endometrial, ovarian, prostate and bladder cancer. 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.
