Positive updated results from Aeterna Zentaris' AEZS-108 Phase 1 trial on CRPC

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/m², 3 at 210 mg/m², and 7 at 267 mg/m². 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/m² 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/m²) 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/m² dose level, the study will be extended into the Phase 2 portion.