Investor Presentation January 2013
Forward Looking Statement This presentation 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 Æterna Zentaris 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 and disclaims 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 to do so by a governmental authority or under applicable law. 2
Corporate Profile A Late-Stage Drug Development Company Addressing Unmet Medical Needs in Oncology and Endocrinology 3
Broad Overall Pipeline Product Candidate Discovery Preclinical Phase 1 Phase 2 Phase 3 Commercial Cetrotide Perifosine Multiple Myeloma Partnered with Merck Serono, Nippon Kayaku, Shionogi Partnered with Handok, Yakult, Hikma In-vitro Fertilization Perifosine Multiple Cancers Partnered with Handok, Yakult, Hikma AEZS-130 GH Deficiency Diagnostic AEZS-130 Ozarelix AEZS-108 AEZS-108 AEZS-112 AEZS-120 AEZS-129-136 AEZS-137 AEZS-125 Cancer Cachexia Prostate Cancer Endometrial Cancer Multiple LHRH-R Positive Cancers Multiple Cancers Prostate Cancer Vaccine Erk & PI3K Inhibitors Disorazol Z (Oncology) LHRH Disorazol Z Partnered with Spectrum, Nippon Kayaku Compound librairy 120,000 Cooperation with NCI 4
Near-Term Value Drivers Perifosine Phase 3 pivotal study in Multiple Myeloma SPA, fast track, orphan drug designation Interim analysis expected in Q1/2013 Potential in other cancers Wholly-owned asset with licensees in Japan, Korea and MENA countries AEZS-108 New cancer targeting approach Approaching Phase 3 in endometrial cancer Exploring clinical efficacy in LHRH-receptor positive cancers Companion diagnostic with Ventana Wholly-owned asset 5
Near-Term Value Driver AEZS-130 NDA filing in early 2013 as first oral diagnostic for adult growth hormone deficiency (AGHD) Proof-of-concept study in cancer-induced cachexia Wholly-owned asset 6
Early-Stage Candidates Development funded by non-dilutive financing Governmental grants (Germany, NIH) CRADAs, Investigator-driven studies NCI screening agreement 7
Significant Market Opportunities
Perifosine in Multiple Myeloma 2 nd most prevalent type of blood cancer in the USA, representing close to 1% of all cancers In 2014, prevalence will be approximately 180,830 cases in the G7 markets Treatable pool relapsed/refractory patient population 2014 3 rd line 2 nd line USA 10,080 14,830 EU-5 11,840 17,410 Japan 2,860 4,200 Source: Decision Resources (March 2012) 9
AEZS-108 in Endometrial Cancer Most invasive gynecologic cancer in women: 47,130 new cases expected in USA in 2012*; 35,600 new cases expected in EU-G5 in 2013**; With about 20% recurrent disease*. No approved drug product in the USA and most of Europe High unmet medical needs *Source: American Cancer Society **Source: Data Monitor 2010 10
AEZS-130 in Growth Hormone Deficiency (GHD) Diagnostic and Therapeutic Estimated number of GHD Diagnostic tests* Cancer Cachexia*** Occurs in ~80 % of patients during the terminal course of disease Attributed as main cause of death in ~20 % of patients Loss of >10 % of premorbid weight = prognostic indicator for poor outcome and decreased survival Cancer cachexia affects about one million patients in North America and Europe USA/CAN EU G5 AGHD** 40,000 36,000 Pediatric GHD 45,000 36,000 Total ~160,000 * Source: Navigant 2009 ** AGHD: Adult Growth Hormone Deficiency *** Source: K.C.H. Fearon et al. (2002) Haehling et al. (2010) 11
Perifosine
Why Could Perifosine Still Work in Multiple Myeloma? Strength of preclinical data Similar studies that predicted success for bortezomib (Velcade ) and lenalidomide (Revlimid ) Concept of synergistic cytotoxicity Three multicenter studies conducted in 171 patients Richardson et al, Blood, 2007 Richardson et al, JCO, 2011 Jakubowiak et al, Br J Haematol., 2012 Even though Phase 2 studies were open-label and noncomparative, the endpoints are rigorous Same P.I. support as for the last 3 drugs approved for MM - Dr. Ken Anderson and Dr. Paul Richardson - for Velcade, Revlimid, and Doxil 13
Perifosine Phase 1/2 Combined With Bortezomib (Velcade ) in MM Efficacy Overall Survival / Time to Progression Patients N ORR Median PFS Median OS All evaluable patients Bortezomib Relapsed Bortezomib Refractory 73 30 (41%) 6.4 months 25 months 20 13 (65%) 8.8 months 30.4 months 53 17 (32%) 5.7 months 22.5 months Richardson et al., Journal of Clinical Oncology, October 2011, ASH, December 2011 14
Perifosine: Phase 3 Study in Multiple Myeloma Randomize ~ 200 patients ~ 200 patients Perifosine 50 mg daily Velcade 1.3 mg/m 2 x 4 d Dex 20 mg x 8 d Evaluate after 6 weeks If SD or >: remain on treatment Placebo 50 mg daily Velcade 1.3 mg/m 2 x 4 d Dex 20 mg x 8 d ~ 265 events (Disease Progression / Death) Median PFS: ~ 7.5 months Median PFS: ~ 5 months Primary Endpoint Progression-Free Survival Each cycle = 21 days SD: stable disease 15
AEZS-108
AEZS-108: Rationale Allows specific targeting of tumor cells expressing the LHRH receptor LHRH receptor Ideal target for personalized medicine approach Expressed in human cancer tissue (e.g. breast (>60%), endometrial (~80%), ovarian (~80%), prostate and bladder cancer) Only detectable in reproductive tissue and pituitary LHRH agonist can be used for targeting LHRH receptors Companion diagnostic test can be developed Positive Phase 2 results in endometrial and ovarian cancer 17
AEZS-108: Trojan Horse for Cancer Cells AEZS-108 (LHRH targeted DOX conjugate) DOX LHRH targeting agent Binding Bypassing the MDR-1 system MDR-1 Internalization Nucleus Migration Apoptosis induction Ref.: Westphalen et al. Int J Oncol. 2000 18
AEZS-108: Phase 1/2 in Castration- and Taxane-Resistant Prostate Cancer Internalization in Circulating Tumor Cells (CTCs) Initial 1-3 hours 24 hours AEZS-108 PSA DAPI Merged Co-localization of AEZS-108 with PSA in CTCs 19
AEZS-108: Phase 2 Recurrent Endometrial Cancer* Patients (n) CR n (%) PR n (%) SD n (%) CBR n (%) TTP (months) OS (months) 43 2 (5%) 11 (26%) 18 (42%) 31 (72%) 7 15 * ITT analysis Treatment regimen: 267 mg/m 2 IV infusion every 3 weeks Toxicity No cardiotoxicity was observed Hematological toxicity was rapidly reversible OS compares favorably to modern triple-combination chemotherapy Ref.: P. Wimberger et al. ESGO 2011 G. Emons et al. German Cancer Congress 2012 20
AEZS-108: Phase 2 Endometrial Cancer Historical Comparison Randomized Trials of Combination First-Line Chemotherapy in Metastatic Endometrial Cancer Study and Regimen Patients Response Rate (RR) (%) Median OS (months) Thigpen et al.* 356 Doxorubicin 22 6.7 Doxorubicin/cyclophosphamide 33 7.3 Fleming et al.* 273 Doxorubicin/cisplatin 34 12.3 Doxorubicin/cisplatin/paclitaxel 57 15.3 AEZS-108**: ORR = 31%, TTP = 7 months and OS = 15 months *No patients had received prior therapy with cytotoxic drugs **Ref.: P. Wimberger et al. ESGO 2011 Ref.: Temkin S, Fleming G: Current treatment of metastatic endometrial cancer. Cancer Control 2009;16:3 21
AEZS-108: Phase 3 in Advanced Recurrent Metastatic Endometrial Cancer Single Phase 3 study planned in recurrent disease following platinum and taxane therapy Comparison against conventional doxorubicin Caelyx/Doxil currently not available and Myocet not approved in the USA Primary endpoint: Overall survival Secondary endpoints: Overall response rate Progression-free survival Safety Companion diagnostic being developed with Ventana 22
AEZS-130
AEZS-130: Orally-Administered Ghrelin Agonist Phase 3 as diagnostic test for Adult Growth Hormone Deficiency (AGHD) First oral diagnostic test in growth hormone deficiency Orphan drug designation in the USA Study completed per SPA agreement Primary efficacy: Achieved > 85% AUC of the Receiver Operating Characteristic (ROC) Curve which determines Specificity and Sensitivity 8 of 10 new AGHD patients correctly classified by pre-specified peak GH threshold level Expect: NDA filing early 2013 24
AEZS-130: Phase 3 Final Results (PPS) Peak Growth Hormone Concentrations Case = AGHD patient JM Garcia et al., ENDO 2012 25
AEZS-130: Cachexia Associated With Cancer Leads to significant weight loss and diminished functional performance. No approved treatments AEZS-130 stimulates food intake and increases body weight in rats and mice Proof-of-concept study in cachexia associated with cancer initiated under CRADA at the Michael E. DeBakey, VA Medical Center, Houston Double-blind, randomized, placebo-controlled dose finding Phase 2A trial in 18 to 26 patients Primary objectives: safety and efficacy Secondary objectives: food intake and changes in appetite, muscle strength, energy expenditure, reward from food and functional brain connectivity 26
AEZS-120 The New Oral Prostate Cancer Immunotherapy (Vaccine)
AEZS-120: Summary Oral Agent Induces cellular and innate immune response May bypass immunotolerance through T-cell suppression and exerts a long-lasting immune response Off-the-shelf product Patent Protection (Platform Technology) 3 applications filed: EP patent granted Development Status EMA classification as ATMP (advanced therapeutic medicinal product) EMA Scientific Advice received with no principle objectives with respect to start Phase 1 CTA/IND filing in preparation 28
Financials
Consolidated Interim Cash Flows (in millions of US dollars) (unaudited) For the three months ended September 30, 2012 Cash and cash equivalents beginning of period 39.8 Cash flows used in operating activities (7.1) Cash flows provided by financing activities 0.4 Exchange rate fluctuation impact and other 0.1 Net change in cash and cash equivalents (6.6) Cash and cash equivalents end of period* 33.2 Average burn rate last 3 months $2.38M per month *Excluding the Offering completed subsequent to quarter-end: $15.2M of net proceeds 30
A Late-Stage Oncology Drug Development Company With a Robust and Balanced Pipeline Perifosine AEZS-108 AEZS-130 Pursue ongoing Phase 3 trial in multiple myeloma Predefined interim analysis in Q1-2013 Initiate pivotal program in endometrial cancer (Phase 3) Initiate triple-negative breast cancer Phase 2 study Update on ongoing Phase 1/2 studies in castration- and taxane-resistant prostate cancer and refractory bladder cancer Update on ongoing companion diagnostic program File an NDA as diagnostic test for AGHD in the USA Update on Phase 2 study in cancer-induced cachexia Early-Stage Development AEZS-120 (immune-therapeutic, oral vaccine) Initiate CTA and Phase 1 in prostate cancer AEZS-112 Continue Phase 1/2 study with new improved formulation AEZS-136 (Dual Kinase Inhibitors) Preclinical studies IND package 31
Back-up Slides
Perifosine
Perifosine in Neuroblastoma 24 patients Age 4-33 [median 9] years Years from diagnosis 2-8 [median 4.5] years Prior therapy Induction plus 2 nd line therapy, all patients 3F8 anti-gd2 antibody, 18 patients Stem cell transplantation, 9 patients Targeted radiotherapy, 2 patients Dose of perifosine 100-200mg/m 2 on day 1 50-75mg/m 2 daily thereafter Ref.: Kushner et al, Poster POC27, Annual Reviews in Neuroblastoma Research, 2012 34
Perifosine in Neuroblastoma Complete Response (CR) in 1 patient Progression-Free Survival (PFS) at 12 months = 56% PFS = 50% ± 11% Perifosine is well tolerated, without major toxicity hence, compatible with excellent quality of life 1 1 Ref.: Kushner et al, Poster POC27, Annual Reviews in Neuroblastoma Research, 2012 35
AEZS-108
AEZS-108: Phase 1/2 Refractory Ovarian Cancer* Patients CR PR SD CBR TTP OS (n) n (%) n (%) n (%) n (%) (months) (months) 42 1 (2%) 7 (17%) 14 (33%) 22 (52%) 3** 12.4 * ITT analysis ** mean 4.4 months Treatment regimen: 267 mg/m 2 IV infusion every 3 weeks Toxicity No cardiotoxicity was observed Hematological toxicity was rapidly reversible OS for Hycamtin or Doxil: 8-9 months 37
AEZS-108: Clinical Phase 1/2 Investigator Initiated Study Prostate Cancer Principal Investigator: Dr. J. Pinski, Norris Comprehensive Cancer Center, USC, Los Angeles Phase 1 lead in with up to 18 patients: Primary goal: Confirm MTD of AEZS-108 in men Phase 2 with up to 37 patients: Primary goal: Clinical benefit defined as non-progression at 12 weeks with no DLT or other toxicity requiring termination of treatment Secondary goal: Time to RECIST and PSA progression, RECIST response and PSA response rate, pain palliation, overall survival and toxicity Correlative studies to investigate potential predictors of response and outcomes including LHRH-R expression on biopsy specimens and on circulating tumor cells 38
AEZS-108: Phase 1/2 in Castration- and Taxane-Resistant Prostate Cancer 16 patients treated with AEZS-108 for up to 8 cycles 3 at 160 mg/m 2 ; 6 at 210 mg/m 2 ; and 7 patients at 267 mg/m 2 Grade 3 and 4 toxicities were hematologic Early evidence of anti-tumor activity even at low dose level PSA regression in 6 patients (46%) Tumor response per RECIST criteria Drug internalization demonstrated in captured circulating tumor cells After completion of 1 additional patient at 210 mg/m 2, the study to be extended in the Phase 2 portion 39
AEZS-108: Phase 1/2 in Castration- and Taxane-Resistant Prostate Cancer: Maximal PSA Response PSA Changes from Baseline 150 Maximal PSA Changes Any Time During Treatment (n=13) 100 50 0-50 -100 Dose Level 1 (n=3) Dose Level 2 (n=3) Dose Level 3 (n=7) S. Liu et al., ASCO GCS, February 2012 40
AEZS-108: Clinical Phase 2 in Urothelial (Bladder) Cancer Patients who Failed Platinum Chemotherapy A Phase 1/2 Trial of AEZS-108 in locally advanced unresectable or metastatic urothelial carcinoma patients who failed platinum based chemotherapy Principal Investigator: Dr. G. Fernandez, Sylvester Comprehensive Cancer Center Miami Phase 1 part with up to 24 patients: Primary goal: Determine the maximally tolerated dose Evaluate pharmacokinetics Phase 2 part with 40 patients: Primary goal: Determine progression-free survival Secondary goal: Response rate (CR + PR), clinical benefit (CR + PR + SD), duration of response, OS and toxicity Evaluate pharmacokinetics in limited subset of patients Translational endpoints: Changes in circulating tumor cell levels as an indicator of clinical benefit Pilot analysis of LHRH-receptor expression on circulating tumor cells as prognostic and predictive variable 41
AEZS-108: Clinical Phase 2 in Triple Negative Breast Cancer Patients who failed after 1 to 3 prior Chemotherapies A randomized, phase 2 trial of AEZS-108 in chemotherapy refractory triple negative (ER/PR/HER2-negative) LHRH-R positive metastatic breast cancer Principal Investigator: Dr. A.G. Montero, University of Miami Miller School of Medicine Randomized Phase 2 trial with up to 74 patients: Primary goal: Evaluate efficacy of AEZS-108 compared to standard single agent cytotoxic chemotherapy (SSCC). Primary efficacy endpoint: duration of progression-free survival (PFS). Secondary goals / endpoints: Efficacy: overall response rate (ORR: CR +PR), clinical benefit rate (CBR: CR + PR + SD), duration of response, time to progression (TTP) and overall survival (OS). Safety: Toxicity profile. Anticipated SSCC drugs per doctor s choice: Paclitaxel, nab-paclitaxel, eribulin, pegylated liposomal doxorubicin (PLD; depending on availability), vinorelbine, gemcitabine, capecitabine Optional cross-over to AEZS-108 after failure on SSCC 42
AEZS-130
AEZS-130: Phase 3 Results AGHD Diagnostic Test AEZS-130 resulted in a greater mean separation between the normal controls and AGHD patients compared to GHRH-ARG Peak GH Responses AEZS-130 Ref.: BMK Biller et al. 2010 5th International Congress of the GRS-IGF Society in New York 44
AEZS-120 The New Oral Prostate Cancer Immunotherapy (Vaccine)
AEZS-120: Genetically Modified Live Bacterium (Salmonella typhi) for Cancer Vaccination Carrier live Salmonella typhi Ty21a Targeting to immune system after oral application Adjuvant / immunostimulating effect, including innate immunity Secretion System Secretion of fusion protein, required for optimal induction of CD8 T-cell responses Choleratoxin Subunit B Non-toxic subunit of choleratoxin Adjuvant effect, advanced targeting to MHC class I processing pathway Prostate Specific Antigen PSA Induction of PSA specific CD8 T-cells for the attack of the tumor Optimal induction of specific and innate antitumor immunity 46
AEZS-120: The Prostate Cancer Immunotherapy Platform Technology Secretion Free antigenic fusion protein Recombinant DNA PSA-CtxB fusion protein 47
AEZS-120: Prostate Cancer Immunotherapy In Vivo Pharmacology Clinical Protocol Comparison of different immunization schedules in a P815-PSA prostate cancer challenge model Median Tumor Volume Tumor Volume (mm³) 400,00 350,00 300,00 250,00 200,00 150,00 100,00 50,00 0,00 0 2 4 6 8 10 12 14 16 Study Day EF1 - naive EF2 - Sl 1C EF3 - Sl 2C EF5 - Sl MoPC 1C EF-6 Sl MoPC 2C EF7 - pcdna PSA Clinical protocols with one or two immunization cycles are feasible 48
Financials
Consolidated Interim Financial Results (in millions of US dollars) (unaudited) For the three months ended Revenues September 30, 2012 September 30, 2011 Sales and royalties 6.8 8.8 License fees and other 0.3 0.7 Operating Expenses 7.1 9.5 Cost of sales 5.6 7.9 R&D costs, net 4.3 5.7 SG&A expenses 2.9 4.1 12.8 17.7 Loss from operations (5.7) (8.2) Net finance (costs) income (0.9) 9.3 Net (loss) income (6.6) 1.1 50
Consolidated Financial Position (in millions of US dollars) (unaudited) As at September 30, 2012 As at December 31, 2011 Cash and cash equivalents 33.2 46.9 Trade and other receivables and other current assets 10.6 13.2 Restricted cash 0.8 0.8 Property, plant and equipment, net 2.1 2.5 Other non-current assets 11.6 12.0 Total assets 58.3 75.4 Payables and other current liabilities 14.3 17.8 Long-term payable (current and non-current portions) - 0.1 Warrant liability (current and non-current portions) 2.7 9.2 Non-financial non-current liabilities* 48.8 52.8 Total liabilities 65.8 79.9 Shareholders deficiency (7.5) (4.5) Total liabilities and shareholders deficiency 58.3 75.4 * Comprised mainly of deferred revenues, employee future benefits and provision 51