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Last updated on April 19, 2014 at 9:20 EDT

Aeterna Zentaris Reports Updated Phase 1 Trial Results for AEZS-108 in Castration- and Taxane-Resistant Prostate Cancer at ASCO GCS Meeting

February 3, 2012

QUÉBEC CITY, Feb. 3, 2012 /PRNewswire/ – Aeterna Zentaris Inc. (NASDAQ:
AEZS) (TSX: AEZ) (the “Company”) today reported positive updated
results for the Phase 1 portion of its ongoing Phase 1/2 study in
castration- and taxane-resistant prostate cancer (CRPC) with AEZS-108 (zoptarelin doxorubicin), the
Company’s targeted cytotoxic luteinizing hormone-releasing hormone
(LHRH) analog. Data showed that AEZS-108 was well tolerated and
demonstrated early evidence of antitumor activity in men with CRPC.
Data were presented by Jacek Pinski, MD, PhD, Associate Professor of
Medicine at the Norris Comprehensive Cancer Center of the University of
Southern California, during a poster session at the American Society of
Clinical Oncology Genitourinary Cancers Symposium which is being held
in San Francisco. Prior interim data on this study were presented at
the European Society of Medical Oncology Congress in September 2011.
The trial is being supported by a three-year US$1.6 million grant from
the National Institutes of Health to Dr. Pinski.

Dr. Pinski stated, “Overall, AEZS-108 has been very well tolerated in
this heavily pre-treated population, though we have met some
hematologic toxicity at the higher dose levels. The efficacy of this
agent, even at lower doses, is impressive and we are eager to complete
the Phase 1 and begin the Phase 2 portion of the study.”

Juergen Engel, PhD, President and CEO of Aeterna Zentaris added, “It is
very encouraging to see that AEZS-108 continues to show good safety and
interesting efficacy data even at this early stage. This compound is a
key element of our personalized medicine approach in oncology, and the
dedicated work of Dr. Pinski and his team ideally fits our commitment
to develop a novel targeted treatment for men suffering from prostate
cancer.”

The Phase 1/2 Study

The poster #D3 titled, A Phase 1 Trial of AEZS-108 in Castration- and Taxane-Resistant Prostate
Cancer
, S.V. Liu, A.V. Schally, T.B. Dorff, D.D. Tsao-Wei, S.G. Groshen, S.
Xiong, D. Hawes, D.I. Quinn, Y.C. Tai, N.L. Block, J. Engel, J. K.
Pinski, (NCT01240629), detailed the use of AEZS-108, in patients with
pre-treated CRPC. This is a single-arm study with a Phase 1 lead-in
portion (testing 3 dose levels) to a Phase 2 clinical trial. The
primary endpoint of the Phase 1 portion is safety. The primary
objective of the Phase 2 portion is to evaluate the clinical benefit of
AEZS-108 for these patients.

Up to 18 men were planned for the Phase 1 lead-in portion which follows
a “3+3″ design to confirm or modify, if needed, the dose established in
a completed Phase 1 trial in women. Patients received AEZS-108
intravenously over 2 hours every 3 weeks for up to 6 cycles, until
progression of the disease, unacceptable toxicity or patient
withdrawal. Premedication included dexamethasone 8 mg. Maximal Prostate
Specific Antigen (PSA) response was calculated using PSA Working Group
2 guidelines. Response Evaluation Criteria in Solid Tumors
(RECIST, v. 1.1) was used to assess response for patients with
measurable disease.

Results

Currently, 13 patients have been treated on 3 dose levels: 3 at 160 mg/m(2),( )3 at( )210 mg/m(2), and 7 at 267 mg/m(2). Overall, AEZS-108 has been well tolerated among this group of heavily
pre-treated older patients. To date, there have been 2 dose limiting
toxicities; both were cases of asymptomatic grade 4 neutropenia at the
267 mg/m(2) dose level and both patients fully recovered. The grade 3 and 4
toxicities were primarily hematologic. There has been minimal
non-hematologic toxicity, most frequently fatigue and alopecia.

Despite the low doses of AEZS-108 in the first cohorts, there is some
evidence of antitumor activity. One patient received 8 cycles (at 210
mg/m(2)) due to continued benefit. Among the 5 evaluable patients with
measurable disease, 4 achieved stable disease. At the time of
submission, a decrease in PSA was noted in 6 patients. Six of 13 (46%)
treated patients have received at least 5 cycles of therapy with no
evidence of disease progression at 12 weeks.

Correlative Studies

As part of correlative studies, a feasibility study to capture
circulating tumor cells (CTCs) using a novel microfluidic device and
test for AEZS-108 internalization was also conducted and feasibility
was demonstrated. The autofluorescence of AEZS-108 allows direct
visualization of internalization and confirmation of drug delivery.
Complete analysis will explore correlation between internalization and
response.

Conclusions

AEZS-108 is generally well tolerated and has demonstrated early evidence
of antitumor activity in men with CRPC. Correlative studies on CTCs
have demonstrated the uptake of AEZS-108 into the targeted tumor. After
completion of 3 additional patients at 210 mg/m(2) dose level, the study will be extended into the Phase 2 portion.

The poster can be viewed on line through the following link.

About AEZS-108

AEZS-108 represents a new targeting concept in oncology using a hybrid
molecule composed of a synthetic peptide carrier and a well-known
chemotherapy agent, doxorubicin. AEZS-108 is the first intravenous drug
in a clinical study that directs the chemotherapy agent specifically to
LHRH-receptor expressing tumors, resulting in more targeted treatment
with less damage to healthy tissue. The product has successfully
completed Phase 2 studies for the treatment of endometrial and ovarian
cancer, and is also in Phase 2 trials in prostate and bladder cancer.
A pivotal trial in endometrial cancer is expected to be initiated in
2012. AEZS-108 has been granted orphan-drug designation by the FDA and
orphan medicinal product designation from the European Medicines Agency
for the treatment of ovarian cancer. An Investigational New Drug in the
U.S. is in place for the treatment of prostate, bladder and
triple-negative breast cancer. Aeterna Zentaris owns the worldwide
rights to AEZS-108.

About Aeterna Zentaris Inc.

Aeterna Zentaris is a late-stage oncology drug development company
currently investigating potential treatments for various cancers
including colorectal, multiple myeloma, endometrial, ovarian, prostate
and bladder cancer. 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

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.


Source: PR Newswire