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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Infinity Reports New Preclinical Data for Saridegib at AACR Supporting Development in Residual Disease Settings

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Apr 1, 2012 – Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today presented new preclinical data for saridegib (IPI-926), its novel oral molecule that inhibits Smoothened, a key component of the Hedgehog pathway. Data presented showed the anti-tumor activity of saridegib in models of residual disease, in which malignant cells remain present after primary treatment. Importantly, these data show that the ability of saridegib to delay tumor recurrence is time dependent and provide rationale for the development of saridegib in residual disease settings, such as ovarian cancer and small cell lung cancer. These data were presented during a mini symposium session at the American Association for Cancer Research (AACR) 103rd Annual Meeting in Chicago, Illinois (Abstract #979).

“In certain cancers, the activity of the Hedgehog pathway is believed to increase in response to therapy and is thought to play a role in tumor recurrence by promoting the survival of residual cancer cells. Today, we showed for the first time that in preclinical models of residual disease, treatment with saridegib post-therapy delays tumor recurrence, but exhibits a time dependence, or an activity window,” stated Vito Palombella, Infinity’s chief scientific officer. “These results are intriguing because they provide insight for the design of clinical trials with Hedgehog pathway inhibitors in a range of residual disease settings and demonstrate the importance of administering saridegib immediately post-therapy.”

Saridegib has been previously shown to delay tumor recurrence following cytoreduction (tumor shrinkage caused by treatment with chemotherapy or targeted therapy) in multiple preclinical models of residual disease, including ovarian, prostate and lung cancer.1,2,3,4 New preclinical data presented today support these findings and show that cytoreduction leads to temporal changes in the tumor microenvironment, as well as upregulation of the Hedgehog ligand and pathway signaling in the tumor cells and surrounding stromal cells, respectively. These new data also suggest that saridegib treatment inhibits the observed Hedgehog pathway activation and may delay tumor recurrence by increasing necrosis, or tumor cell death, post-therapy. Saridegib showed the greatest inhibition of tumor regrowth when administered within 10 days of completing primary therapy, suggesting that there may be a window of activity during which the effects of saridegib are greatest. This presentation, “The anti-tumor activity of the Smoothened inhibitor saridegib (IPI-926) in models of residual disease is time dependent,” may be found in the Publications Archive on Infinity’s website, http://www.infi.com/product-candidates-publications.asp.

The window of activity for saridegib in preclinical models was confirmed in a model of ovarian cancer through a collaboration with Bo Rueda, Ph.D., associate director, Vincent Center for Reproductive Biology, Massachusetts General Hospital and associate professor, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School. A poster highlighting this work, “Hedgehog pathway inhibition delays regrowth of ovarian cancer following paclitaxel and carboplatinum only if initiated immediately after completion of chemotherapy,” will be presented during a poster session on Tuesday, April 3, 2012, from 9:00 a.m. — 1:00 p.m. ET in McCormick Place West, Hall F, Poster Section 11 (Abstract #3285).

About the Hedgehog Pathway and Saridegib

Malignant activation of the Hedgehog pathway occurs in a broad range of cancers through multiple mechanisms, including signaling directly to tumor cells, signaling to tumor progenitor cells and signaling to the tumor microenvironment. Saridegib is a small molecule that inhibits Smoothened, a key component of the Hedgehog pathway. Smoothened inhibition represents a significant anti-cancer opportunity for addressing a number of difficult-to-treat cancers by disrupting malignant activation of the pathway.

Saridegib is currently being evaluated in a randomized, double-blind Phase 2 clinical trial designed to evaluate the safety and efficacy of saridegib compared to placebo in patients with metastatic or locally advanced, inoperable chondrosarcoma, an incurable cancer of the cartilage. In addition, an exploratory Phase 2 trial is under way evaluating saridegib as a single agent in patients with myelofibrosis, a cancer of the bone marrow. In Phase 1 trials, saridegib has been generally well-tolerated and showed evidence of clinical activity. These clinical trials build upon a robust set of supporting data that provide a strong rationale for evaluating the potential of IPI-926 for treatment across a broad range of cancers.

About Infinity Pharmaceuticals, Inc.

Infinity is an innovative drug discovery and development company seeking to discover, develop and deliver to patients best-in-class medicines for difficult-to-treat diseases. Infinity combines proven scientific expertise with a passion for developing novel small molecule drugs that target emerging disease pathways. Infinity’s programs focused on the inhibition of the Hedgehog pathway, heat shock protein 90 and phosphoinositide-3-kinase are evidence of its innovative approach to drug discovery and development. For more information on Infinity, please refer to the company’s website at http://www.infi.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include those regarding the potential of Hedgehog pathway inhibition for addressing multiple, difficult-to-treat cancers, and the potential of saridegib in residual disease settings such as ovarian cancer and small cell lung cancer. Such statements are subject to numerous factors, risks and uncertainties that may cause actual events or results to differ materially from the company’s current expectations. For example, there can be no guarantee that Infinity’s strategic alliance with Mundipharma will continue for its expected term or that it will fund Infinity’s programs as agreed, that any product candidate Infinity is developing will successfully complete necessary preclinical and clinical development phases, or that development of any of Infinity’s product candidates will continue. Further, there can be no guarantee that any positive developments in Infinity’s product portfolio will result in stock price appreciation. Management’s expectations could also be affected by risks and uncertainties relating to: Infinity’s results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Infinity’s ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures, including in connection with business development activities; development of agents by Infinity’s competitors for diseases in which Infinity is currently developing its product candidates; and Infinity’s ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing. These and other risks which may impact management’s expectations are described in greater detail under the caption “Risk Factors” included in Infinity’s annual report on Form 10-K for the year ended December 31, 2011, filed with the Securities and Exchange Commission on March 13, 2012. Any forward-looking statements contained in this press release speak only as of the date hereof, and Infinity expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

1 McCann CK; Growdon WB; Kulkarni-Datar K; Curley MD; Friel, AM, et al. Inhibition of Hedgehog Signaling Antagonizes Serous Ovarian Cancer Growth in a Primary Xenograft Model. PlosOne 2011; 6(11): 1-9.

2 Mandley E, White K, Faia K, Travaglione V, McGovern K and MacDougall J. The Hh inhibitor IPI-926 delays tumor re-growth of a non-small cell lung cancer xenograft model following treatment with an EGFR targeted tyrosine kinase inhibitor. Poster session presented at American Association for Cancer Research 103rd Annual Meeting; 2010 April 17-21; Washington, D.C.

3 Travaglione V, Peacock C, MacDougall J, McGovern K, Cushing J, et al. A Novel Hh pathway inhibitor, IPI-926, delays recurrence post-chemotherapy in a primary human SCLC xenograft. Poster session presented at American Association for Cancer Research 101st Annual Meeting; 2008 April 12-16; San Diego, CA.

4 Proctor J, Travaglione V, Deyneko I, White K, Read MR, et al. Hedgehog Signaling in Castration Resistant Prostate Cancer. Mini-symposia presented at American Association for Cancer Research 103rd Annual Meeting; 2010 April 17-21; Washington, D.C.

Contact: Infinity Pharmaceuticals, Inc.
Jaren Irene Madden, 617-453-1336
Jaren.Madden@infi.com
http://www.infi.com
or
Media:
Liz Falcone, 617-761-6727
Liz.Falcone@fkhealth.com

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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ARIAD Presents New Preclinical Data on Ponatinib and AP26113

Both Tyrosine Kinase Inhibitors Overcome Drug Resistance Due to “Gatekeeper” Mutations Of Multiple Oncogenic Targets

CAMBRIDGE, Mass. & CHICAGO–(BUSINESS WIRE)–Apr 2, 2012 – ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced the presentation of new preclinical data on its investigational pan-BCR-ABL inhibitor, ponatinib, and its investigational dual EGFR-ALK inhibitor, AP26113, at the American Association for Cancer Research Annual Meeting in Chicago. Both drug candidates, discovered using ARIAD’s structure-based drug design platform, are potent inhibitors of multiple “gatekeeper” mutations that have been shown to confer clinical resistance to other targeted cancer medicines.

The first study, “Ponatinib, a potent pan-BCR-ABL inhibitor, retains activity against gatekeeper mutants of FLT3, RET, KIT, PDGFR and FGFR1,” was presented yesterday and shows that ponatinib overcomes resistant gatekeeper mutations well beyond BCR-ABL — the drug‘s target in chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) — in other clinically relevant tyrosine kinase targets.

The preclinical research conducted by ARIAD scientists assessed the activity of ponatinib using cell lines expressing activated forms of FLT3, RET, KIT, PDGFR and FGFR1, each a kinase target associated with a specific tumor type. Ponatinib potently inhibited the activity of these kinases and maintained potent activity against gatekeeper variants that have been shown to cause resistance to other tyrosine kinase inhibitors in acute myeloid leukemia, medullary thyroid cancer, gastrointestinal stromal tumor (GIST) and rare forms of leukemia driven by these tyrosine kinases.

“Ponatinib was designed to block the abnormal tyrosine kinase, BCR-ABL, which drives CML and Ph+ALL,” said Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer of ARIAD. “The structural design feature that allows ponatinib to evade the BCR-ABL T315I gatekeeper mutation also enables the molecule to overcome analogous mutations in its other kinase targets. We are actively working with academic collaborators to set up clinical trials aimed at determining the potential role of ponatinib in these additional forms of drug-resistant cancer.”

A second abstract, “AP26113 is a dual ALK/EGFR inhibitor: Characterization against EGFR T790M in cell and mouse models of NSCLC,” will be presented today and describes the activity of AP26113, a dual inhibitor of EGFR and ALK, to overcome gatekeeper mutations of these targets. This preclinical research further confirms that AP26113 is a potent, reversible inhibitor of the T790M gatekeeper mutation of epidermal growth factor receptor (EGFR). Activated EGFR occurs in approximately 250,000 lung cancer patients worldwide, and the single T790M mutation accounts for over 50 percent of resistance to tyrosine kinase inhibitors in these patients who have limited treatment options available.

This poster also presents, for the first time, preclinical data demonstrating that AP26113 potently inhibits non-small cell lung cancer (NSCLC) cell lines that express an activating translocation of the ROS1 tyrosine kinase. Such ROS1 mutations have recently been identified as a feature of approximately two percent of all NSCLC, representing another area for further investigation of AP26113 in NSCLC patients in need of better therapeutic choices.

About ARIAD

ARIAD Pharmaceuticals, Inc. is an emerging global oncology company focused on the discovery, development and commercialization of medicines to transform the lives of cancer patients. ARIAD’s approach to structure-based drug design has led to three internally discovered, molecularly targeted product candidates for drug-resistant or difficult-to-treat cancers, including certain forms of chronic myeloid leukemia, soft tissue and bone sarcomas and non-small cell lung cancer. For additional information, visit http://www.ariad.com or follow ARIAD on Twitter.

This press release contains “forward-looking statements” including, but not limited to, updates on clinical, preclinical and regulatory developments for our product candidates. Forward-looking statements are based on management’s expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, preclinical data and early-stage clinical data that may not be replicated in later-stage clinical studies, the costs associated with our research, development, manufacturing and other activities, the conduct, timing and results of pre-clinical and clinical studies of our product candidates, the adequacy of our capital resources and the availability of additional funding, and other factors detailed in the Company’s public filings with the U.S. Securities and Exchange Commission. The information contained in this press release is believed to be current as of the date of original issue. The Company does not intend to update any of the forward-looking statements after the date of this document to conform these statements to actual results or to changes in the Company’s expectations, except as required by law.

Contact: For ARIAD Pharmaceuticals, Inc.
For Investors
Maria E. Cantor, 617-621-2208
maria.cantor@ariad.com
or
For Media
Lynn Granito, 212-253-8881
lgranito@berrypr.com

Posted: April 2012

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