In Vitro and In Vivo Data Show AEZS-126 as a Promising Oral Compound for Future Clinical Development in Cancer
QUEBEC CITY, April 20 /PRNewswire-FirstCall/ - Aeterna Zentaris Inc. (the “Company”), a late-stage drug development company specialized in oncology and endocrine therapy, today presented a poster on dual Erk/PI3K inhibitors and made an oral presentation on its selective Erk inhibitors, at the American Association for Cancer Research (AACR) Annual Meeting in Washington, D.C.
Oral Presentation, Abstract #3856
Entitled, “A highly selective Erk-inhibitor with antiproliferative efficacy and the potential for combination therapy with modulators of the PI3K pathway”, I. Seipelt, L. Blumenstein, S. Baasner, G. Mueller, B. Aicher, M. Teifel, E. Guenther, M. Gerlach, the presentation outlines data on selective Erk inhibitors as antiproliferative agents either as monotherapy or in combination with inhibitors of the PI3K/Akt pathway.
Results
Aeterna Zentaris has identified small molecular compounds that inhibit Erk in the low nanomolar range and show an excellent selectivity profile. Other serine threonine, lipid or tyrosine kinases are not inhibited at concentrations up to 10(micro)M. Further studies revealed an ATP competitive mode of action and the potent inhibition of the cellular downstream target Rsk1 in tumor cells with an IC50 value of 158nM. The lead structure AEZS-131 produces cell cycle arrest in G1 and results in growth inhibition of cancer cells. Furthermore, the potential of combination therapy of AEZS-131 with inhibitors of the PI3K pathway was addressed and synergistic anti-proliferative activity was observed e.g. with the selective PI3K inhibitor, AEZS-126.
Conclusion
These results support further evaluation of selective Erk inhibitors as antiproliferative agents either as monotherapy or in combination with inhibitors of the PI3K/Akt pathway.
Poster #4474
Entitled, “Dual inhibitors for PI3K and Erk induce growth inhibition of tumor cells”, I. Seipelt, M. Gerlach, S. Baasner, L. Blumenstein, G. Mueller, B. Aicher, E. Guenther, M. Teifel, the poster focuses on key characteristics of the compound class that led to the selection of AEZS-132 for in vivo evaluation.
Results
A multi-parameter optimization program for kinase inhibitor selectivity, cellular efficacy, physicochemical and in vitro ADMET properties has led to the discovery of a small molecular compound class with an uniquely advantageous dual kinase inhibition profile. These ATP competitive compounds inhibit Erk and PI3K in the nanomolar range and exert high selectivity against other serine threonine and tyrosine kinases. For the frontrunner compound, AEZS-132, antitumor efficacy was demonstrated in several human tumor cell lines including HCT116, A549, MDA-MB 468, and PC-3. In in vivo antitumor studies, significant antitumor activity was observed at 30 mg/kg daily oral administration of AEZS-132 in HCT116 and Hec1B tumor xenografts, with T/C values of 0.33 (HCT116) and 0.57 (Hec1B), respectively. Furthermore, target modulation has been demonstrated in tumor samples.
Conclusion
The optimization of Aeterna Zentaris’ pyridopyrazine compounds towards dual inhibition of PI3K and Erk resulted in the identification of AEZS-132, a unique dual inhibitor of PI3K and Erk with a favourable pharmacology and ADMET profile for further evaluation as an antitumor agent.
Juergen Engel, Ph.D., President and CEO of Aeterna Zentaris stated, “These results not only demonstrate the potential of Erk/PI3K inhibitor compounds as novel treatments in oncology, but also position us as a leading player in this field beyond perifosine, our Akt-inhibitor currently in Phase 3 trials for multiple myeloma and colorectal cancer.”
About Aeterna Zentaris Inc.
Aeterna Zentaris Inc. is a late-stage drug development company specialized in oncology and endocrine therapy. News releases and additional information are available at www.aezsinc.com.
Forward-Looking Statements
This press release contains forward-looking statements made pursuant to the safe harbor provisions of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements involve known and unknown risks and uncertainties, which 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 the 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 except if we are required by a governmental authority or applicable law.
CONTACT: Investor Relations: Ginette Vallieres, Investor Relations
Coordinator, (418) 652-8525 ext. 265, gvallieres@aezsinc.com; Media
Relations: Paul Burroughs, Director of Communications, (418) 652-8525 ext.
406, pburroughs@aezsinc.com