Aeterna Zentaris Presents Preclinical Data for Its Anti-Cancer PI3K/ Erk 1/2 Inhibitor, AEZS-136, at AACR Meeting

AEZS-136 shows synergy and efficacy in human tumor cells

QUÉBEC CITY, April 3, 2012 /PRNewswire/ – Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the “Company”) today announced that a poster on its novel orally active anticancer PI3K/Erk 1/2 inhibitor, AEZS-136, showed the compound’s unique inhibition and excellent activity against PI3K and Erk signaling pathways, as well as being well tolerated. The poster titled, “Dual inhibition of PI3K and Erk1/2 shows synergy and efficacy in human tumor cells, either by using drug combinations or novel dual PI3K/Erk inhibitors”, I. Seipelt, M. Gerlach, L. Blumenstein, G. Mueller, E. Guenther, J. Engel and M. Teifel, was presented by Irene Seipelt, PhD, Director, Preclinical Development at Aeterna Zentaris, at the American Association for Cancer Research Annual Meeting currently held in Chicago.

Results

The anti-proliferative efficacy of AEZS-136 was evaluated in more than 40 human tumor cell lines including breast, ovary, endometrium, multiple myeloma, lung, melanoma, colon, leukemia and prostate cancer cells. In vitro ADMET properties were also widely assessed, while in vivo pharmacokinetics (PK) and anti-tumor efficacy was explored. AEZS-136 was well tolerated and showed dose-dependent inhibition of human colon tumor growth of up to 72% in a Hct116 mouse model.

Conclusions

•Effective dual targeting of Raf-Mek-Erk and PI3K-Akt pathway
•Unique inhibitor with excellent activity against PI3K and Erk
•Induction of G1 arrest and apoptosis
•Broad anti-proliferative activity in vitro
•Favorable in vitro ADMET and in vivo PK profile
•Well tolerated up to daily doses of 90mg/kg for 4 weeks
•In vivo anti-tumor efficacy after oral administration
Juergen Engel, Ph.D., Aeterna Zentaris’ President and CEO, commented, “The preclinical data presented yesterday, confirms that AEZS-136 has a unique advantageous dual PI3K /Erk kinase inhibition profile which could prove to be more efficient than single pathway inhibition. Furthermore, AEZS-136 has shown to be well tolerated. Following these encouraging preclinical data, we are currently moving this promising compound into the clinical development stage.”

To consult a copy of the poster, please click here.

About AEZS-136

AEZS-136 is an integral part of the Company’s kinase research program comprising the investigation of different compounds for single Erk inhibition, single PI3K inhibition and dual Erk/PI3K kinase inhibition. AEZS-136 selectively inhibits the kinase activity of Erk 1/2 and class 1 PI3Ks, enabling simultaneous inhibition of the Raf-Mek-Erk and the PI3K-Akt signaling cascades. AEZS-136 was discovered using our proprietary compound library and high throughput screening technology.

About Aeterna Zentaris Inc.

Aeterna Zentaris is a late-stage oncology drug development company currently investigating potential treatments for various cancers. 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 http://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 risk that safety and efficacy data from any of our Phase 3 trials may not coincide with the data analyses from previously reported Phase 1 and/or Phase 2 clinical trials, 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.

Posted: April 2012

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Acceleron’s ACE-041 Combined with a VEGF Inhibitor Shows Potent Activity in Preclinical Model of VEGF-Resistant Renal Cell Carcinoma

— Enhanced Anti-Tumor Activity Achieved via Combination of Two Distinct Anti-Angiogenic Drugs presented at the AACR Annual Meeting 2012 —

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Apr 3, 2012 – Acceleron Pharma, Inc., a biopharmaceutical company developing protein therapeutics for cancer and orphan diseases, announced that collaborators at Beth Israel Deaconess Medical Center presented preclinical data today at the American Association for Cancer Research (AACR) Annual Meeting 2012 which showed that ACE-041, an activin-receptor like kinase 1 (ALK1) receptor ligand trap, when used in combination with sunitinib, inhibited tumor growth in a model of VEGF-inhibitor-resistant renal cell carcinoma (RCC).

Anti-angiogenesis therapies, including the VEGF-inhibitor sunitinib, are currently the standard of care in metastatic RCC. While these treatments cause tumor shrinkage and extend progression-free survival in many patients, the responses are typically short-lived due to the development of drug resistance. Mice bearing A498 and 786-0 human RCC xenografts that receive anti-VEGF treatment mirror this clinical experience with a period of tumor stabilization that is followed by the restoration of angiogenesis and resumption of growth despite continued drug administration. The preclinical data, presented by Rupal Bhatt, M.D., Ph.D., Assistant Professor, Hematology-Oncology, Beth Israel Deaconess Medical Center provide evidence that combining two distinct anti-angiogenic drugs, a VEGF inhibitor and ACE-041, may produce an enhanced therapeutic effect in the treatment of metastatic RCC.

Preclinical Study Description and Results

Two renal cell carcinoma cell lines (A498 and 786-O) were used in a mouse xenograft model. In each tumor cell line, mice treated with the combination of ACE-041 and sunitinib slowed tumor growth to a greater extent than either agent alone. Additionally, the combination of ACE-041 and sunitinib prevented the restoration of tumor perfusion during the resistant phase of sunitinib-alone treatment and lowers tumor perfusion to a greater extent than sunitinib-alone.

“These data demonstrate that blocking ALK1 ligand signaling, either alone or in combination with other anti-angiogenesis therapies, may be an attractive strategy for treatment of renal cell carcinoma,” said Dr. Bhatt.

“There is increasing evidence that combining anti-angiogenesis inhibitors with distinct mechanisms of action, such as a VEGF inhibitor with an ALK1 ligand trap, like ACE-041, can more effectively inhibit tumor angiogenesis,” said Matthew Sherman, M.D., Chief Medical Officer at Acceleron. “We believe this approach holds great promise and we’re excited to pursue Phase 2 studies of ACE-041 in combination with VEGF inhibitors later this year.”

About ACE-041

ACE-041 is an ALK1 ligand trap that inhibits angiogenesis by preventing BMP9 and BMP10, members of the TGFβ protein superfamily, from interacting with activin receptor-like kinase 1 (ALK1), a receptor found on proliferating endothelial cells. ACE-041 inhibits ALK1 signaling, which is required for the development of mature, functional capillary networks. In animal studies, treatment with ACE-041 inhibits tumor angiogenesis and growth. In a clinical study of patients with advanced, refractory solid tumors, treatment with ACE-041 was generally well-tolerated and antitumor activity was observed, resulting in tumor shrinkage and stabilization of disease. ACE-041 is being studied in a Phase 2 clinical trial in patients with squamous cell carcinoma of the head and neck.

About Acceleron

Acceleron is a privately-held biopharmaceutical company committed to discover, develop, manufacture and commercialize novel protein therapeutics for orphan diseases and cancer. Acceleron’s scientific approach takes advantage of its unique insight to discover first-in-class therapies based on the TGF-β protein superfamily. Acceleron utilizes proven biotherapeutic technologies and capitalizes on the company’s internal GMP manufacturing capability to advance its therapeutic programs rapidly and efficiently. The investors in Acceleron include Advanced Technology Ventures, Alkermes, Avalon Ventures, Bessemer Ventures, Celgene, Flagship Ventures, MPM BioEquities, OrbiMed Advisors, Polaris Ventures, QVT Financial, Sutter Hill Ventures and Venrock. For further information on Acceleron, please visit http://www.acceleronpharma.com.

Contact: Acceleron Pharma:
Steven Ertel, 617-649-9234
Chief Business Officer
or
Suda Communications LLC
Maureen L. Suda, 585-387-9248
Media

Posted: April 2012

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Oncoprex Shows Synergistic Tumor Suppression in Combination with AKT Inhibitor MK2206

Data Presented at the American Association for Cancer Research 2012 Annual Meeting

CHICAGO and AUSTIN, Texas, April 2, 2012 /PRNewswire/ — Genprex, Inc. — New data demonstrating the anti-cancer activities of Oncoprex® were presented at the 2012 Annual Meeting of the American Association for Cancer Research (AACR) in Chicago, IL.  The study, “Synergistic antitumor activity of AKT inhibitor MK2206 and FUS1 nanoparticles in LKB1 mutant NSCLC” (Meng J, Lara-Guerra H, Ji L, Roth JA) is authored by a team of investigators from The University of Texas MD Anderson Cancer Center.  The paper is included in the Proceedings of the Annual Meeting of the American Association for Cancer Research, 2012, Abstract 870.  The preclinical study demonstrates that when Oncoprex is combined with Merck’s MK2206[1], the combination of therapies is more effective in suppressing growth in LKB1 mutant tumors than either of the single agents in animal models bearing H322 LKB1-mutant human lung cancer tumors.  The treatment with the combination of Oncoprex and MK2206 resulted in tumor volume reduction of greater than 2.5 times the tumor reduction achieved with MK2206 alone.

A phase I clinical trial evaluating intravenous Oncoprex monotherapy, also known as FUS1 nanoparticles, demonstrated antitumor activity in lung cancer patients.  Previously published animal studies showed synergistic cancer-killing activity when Oncoprex is combined with a variety of kinase inhibitory agents including erlotinib and gefitinib.  A phase I/II clinical trial evaluating Oncoprex combined with Tarceva® (erlotinib) in lung cancer patients without the EGF receptor mutation or patients who have failed Tarceva therapy will initiate in 2012. 

David J. Tomasso, chief operating and business officer at Genprex commented, “Many patients cannot benefit from targeted cancer therapies due to the patient’s genomic characteristics. We are developing Oncoprex combination therapies to expand patient populations benefiting from targeted therapies and to unlock the unrealized potential of a variety of targeted kinase inhibitory drugs. This study broadens the potential application of Oncoprex to include combinations with AKT inhibitors such as MK2206.”

Contact:      
David Tomasso
Chief Operating and Business Officer
Genprex, Inc.
Phone: 512-597-5900
http://www.genprex.com
[1] MK2206, an investigational cancer therapy developed by Merck & Co., is a highly selective non-ATP competitive allosteric inhibitor of AKT currently being evaluated in early-phase clinical trials for treatment of cancer patients with solid tumors.

SOURCE Genprex, Inc.

Posted: April 2012

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