QUEBEC CITY, April 4 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") today announced that two posters on its lead anticancer agent, perifosine, were presented at the 102nd annual meeting of the American Association for Cancer Research currently held at the Orange County Convention Center in Orlando, Florida.
Entitled, "Antitumor activity of novel Akt inhibitor, perifosine in gastric cell lines",Tae Soo Kim, Hyo Song Kim, Bo Ram Kwan, Chan Hee Park, Hei-Cheul Jeung, Woo Ick Jang, Juergen Engel, Hyun Cheol Chung, Jae Kyung Roh, Sun Young Rha, (Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea).
Perifosine showed single agent anti-proliferative activity in a variety of gastric cancer cell lines. In 8/13 cell lines resistant to 5-FU, perifosine showed a synergistic antiproliferative activity with 5-FU. In 72% of cell lines, high basal levels of pAkt were detected. Treatment with perifosine reduced tumor growth in nude mice inoculated subcutaneously with the YCC 2 gastric cancer cell line. Finally, an MTT based microarray analysis was performed to identify pharmacogenomic classifiers for synergy in 5-FU resistant cell lines.
Perifosine demonstrated antitumor activity in several gastric cancer cell lines. Furthermore, perifosine enhanced the antitumor activity of 5-FU in parts of the cell lines - including 5-FU resistant cell lines. 5-FU is the active metabolite of the prodrug Xeloda, which is approved for the treatment of advanced gastric cancer in many countries including Japan and Korea.
Entitled "The Akt inhibitor Perifosine strongly enhances the antitumor and antivascular activity of CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)" , Arianna Giacomini, Silvia L. Locatelli, Marco Righi, Loredana Cleris, Paolo D. Longoni, Marco Milanesi, Maura Francolini, Michele Magni, Massimo Di Nicola, Alessandro M. Gianni, Carmelo Carlo-Stella (Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori Milano and University of Milan, Milan, Italy).
Pro-apoptotic TRAIL receptors present on tumor cells are known to represent a potential pharmaceutical target for cancer treatment. Perifosine stimulated the expression of pro-apoptotic TRAIL receptors on the multiple myeloma KMS-11 cell line, substantially reduced the levels of phosphorylated Akt and significantly enhanced the sensitivity of these cells for trail induced apoptosis. The same molecular effects were noted in the non-Hodgkin lymphoma cell line SU-DHL-4V. In this TRAIL resistant cell line, perifosine treatment substantially enhanced the cytotoxicity of TRAIL treatment to similar levels observed in the TRAIL sensitive multiple myeloma cell line.
The synergistic activity was confirmed in NOD/SCID mice xenograft models, where perifosine induced a down-modulation of Akt expression as well as TRAIL receptor upregulation in tumor cells and tumor endothelial cells.
Perifosine markedly enhanced the antitumor activity of the cellular TRAIL based treatment and was able to overcome TRAIL resistance both in vitro and in vivo. The results are in line with other studies demonstrating the synergistic effects of perifosine with cytotoxic drugs, including bortezomib and 5-FU.
Juergen Engel, Ph.D. Aeterna Zentaris President and Chief Executive Officer, commented, "Gastric cancer represents a significant threat especially in Asia. This preclinical work demonstrates the potential of perifosine especially in combination with Xeloda for the treatment of gastric cancer. Moreover, both posters are in line with previous data and the clinical observations emphasizing the benefit of combining perifosine with cytotoxic drugs in different oncological indications."
Perifosine is a novel, oral anticancer treatment that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway. The product works by interfering with membranes of cancer cells thereby inhibiting Akt signaling which then affects cell death, growth, differentiation and survival. Perifosine, in combination with chemotherapeutic agents, is currently being studied for the treatment of multiple myeloma, colorectal cancer and other cancers, and is the most advanced anticancer agent of its class. Perifosine, as monotherapy, is being explored in other indications. The US Food & Drug Administration ("FDA") has granted perifosine orphan-drug designation in multiple myeloma and neuroblastoma, and Fast Track designations in both multiple myeloma and refractory advanced colorectal cancer. Additionally, an agreement was reached with the FDA to conduct the Phase 3 trials in both of these indications under a Special Protocol Assessment. Perifosine has also been granted orphan medicinal product designation from the European Medicines Agency ("EMA") in multiple myeloma. Furthermore, perifosine has received positive Scientific Advice from the EMA for both the multiple myeloma and advanced colorectal cancer programs, with ongoing Phase 3 trials for these indications expected to be sufficient for registration in Europe. Perifosine rights have been licensed to Keryx Biopharmaceuticals for North America, Yakult Honsha for Japan and to Handok for Korea.
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.
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.
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