QUÉBEC CITY, April 10, 2013 /PRNewswire/ - Aeterna Zentaris Inc.
(NASDAQ: AEZS) (TSX: AEZ) (the "Company") today presented encouraging
updated proof-of-concept results for Disorazol Z cytotoxic conjugates,
such as AEZS-125 and AEZS-138, in human ovarian and endometrial cancer
xenograft models. Results further showed the compounds' high potential
for the treatment of luteinizing hormone-releasing hormone ("LHRH")
receptor positive tumors. Data were presented earlier today by Babette
Aicher, PhD, the Company's Director of Preclinical Development, during
a poster presentation at the American Association for Cancer Research
("AACR") annual meeting currently being held in Washington D.C. The
study is funded through a grant from the German Ministry of Education
Juergen Engel, PhD, Aeterna Zentaris President and CEO stated,
"Disorazol Z cytotoxic conjugates such as AEZS-125 and AEZS-138 are an
extension of our AEZS-108 innovative LHRH-targeted platform in
oncology. These results confirm the encouraging data presented at the
ENA Symposium in November 2012, and will enable us to better select a
specific drug candidate for further preclinical development expected to
start during this quarter."
Conjugates of D-Lys6-LHRH and Disorazol Z retained strong binding to the LHRH receptor and
showed potent inhibition of tubulin polymerization. Cellular
cytotoxicity of the conjugates was in the low nanomolar EC50 range. Increased cytotoxicity in cells over-expressing the LHRH
receptor, support receptor targeting as a mechanism of action;
AEZS-125 and AEZS-138 have been identified as the most promising
The LHRH receptor-dependent efficacies of Disorazol Z - D-Lys6-LHRH conjugates in vitro and in mouse xenograft models that were presented, support the
principle of tumor targeting by the LHRH receptor as already employed
by the drug candidate AEZS-108, which is currently in a Phase 3 study
in endometrial cancer and in Phase 2 studies in triple-negative breast
cancer, bladder cancer and prostate cancer.
The poster, "LHRH receptor targeting as mechanism of anti-tumor activity for
cytotoxic conjugates of Disorazol Z with the LHRH receptor agonistic
peptide D-Lys6-LHRH", B. Aicher et al. can be viewed through this link.
About Disorazol Z
Disorazol Z is a novel natural compound, with outstanding cytotoxic
activity, isolated from the myxobacterium Sorangium cellulosum. Disorazol Z, a macrocyclic polyketide, is produced by a fermentation
process providing high yield and purity. Besides tubulin binding,
Disorazol Z has pro-apoptotic properties and has been shown to arrest
cancer cells in G2M stage of the cell cycle at subnanomolar
concentrations. Disorazol Z is an ideal partner for the formation of
cytotoxic conjugates with peptides, proteins, and antibodies to
selectively target cancer cells.
About Disorazol Z cytotoxic conjugates such as AEZS-125 and AEZS-138
AEZS-125 and AEZS-138 are novel cytotoxic conjugates based on the
natural compound Disorazol Z and the LHRH receptor agonist D-Lys6-LHRH. The peptide part directs the conjugates specifically to LHRH
receptor expressing tumor cells, and mediates binding and uptake via
endocytosis. Within the cancer cell, the conjugates are cleaved and
Disorazol Z can deploy its potent anti-proliferative activity.
According to the literature, LHRH receptors occur in a number of human
tumors, specifically in about 80% of ovarian and endometrial cancers.
They are also expressed in prostate, urinary bladder and
triple-negative breast cancer, while they are rarely found in normal
tissues, except for the pituitary gland and reproductive organs. The
LHRH receptor displays ideal properties for selective drug targeting.
About Aeterna Zentaris
Aeterna Zentaris is an oncology and endocrinology drug development
company currently investigating treatments for various unmet medical
needs. The Company's pipeline encompasses compounds at all stages of
development, from drug discovery through to marketed products. For more
information, 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 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.