Transcript Document

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Investor Presentation
March 2010
Forward-Looking Statements
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 the
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 by a governmental authority or applicable law.
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Æterna Zentaris
Late-Stage Drug Development
Company Specialized in Oncology
and Endocrinology
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Æterna Zentaris
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Management team
Juergen Ernst
Executive Chairman
30+ years experience: Solvay
Juergen Engel, Ph.D.
President and CEO
30+ years experience: ASTA Medica
Paul Blake, M.D.
Senior VP and CMO
25+ years experience: Cephalon, SmithKline Beecham
(now GSK), ICI Pharmaceuticals (now Astra Zeneca)
Nicholas J. Pelliccione, Ph.D.
Senior VP, Regulatory Affairs and QA
20+ years experience: Chugai Pharma USA , ScheringPlough
Matthias Seeber, M.B.A.
Senior VP, Administration and Legal Affairs
15+ years experience: Altana AG, Deka Investment
Management, Dresdner Bank AG
Dennis Turpin, CA
Senior VP and CFO
20+ years experience: Coopers & Lybrand (now PWC)
Late-Stage Oncology & Endocrinology
Pipeline
Compound
Perifosine
Indication
Preclinical
Phase 1
Phase 2
Multiple Myeloma
Partners: Keryx (North America) & Handok (Korea)
Metastatic Colon Cancer
Partners: Keryx (North America) & Handok (Korea)
Kidney Cancer and Others
Partners: Keryx (N. America) & Handok (Korea)
Phase 3
Endometrial Cancer
AEZS-108
Ovarian Cancer
Other Cancers
AEZS-112
Solid Tumor
AEZS-120
Tumor Vaccine
Prostate Cancer
AEZS-129/131
PI3K/Erk
Inhibitor
Oncology
Cetrotide®
In Vitro Fertilization
AEZS-130
(SolorelTM)
Diagnostic – Adult Growth
Hormone Deficiency
AEZS-130
(macimorelin)
Therapeutic –
Endocrinology
AEZS-123
Ghrelin
Antagonist
Endocrinology
Partners: Merck Serono, Nippon Kayaku / Shionogi (Japan)
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Commercial
Vision & Business Strategy of
Æterna Zentaris
 Our vision: to become a fully-integrated specialty
biopharmaceutical company
 Our Business Development Strategy
− To retain co-marketing and/or co-promotion rights for our
products
− To retain rights for certain territories for our products
− To have access to the development data of Licensee at
no cost outside their territory
• Example: Perifosine (Keryx for North America and
Handok for Korea)
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Perifosine: Abnormalities in the PI3K/Akt
Signaling Pathway in Cancer
Oral Akt inhibitor: Induction of apoptosis (cell death) &
Inhibition of cellular proliferation and survival
Brain
Thyroid
Breast
Lung
Blood (MM)
Kidney
Ovary
Pancreas
Liver
Colon
Prostate
Skin
Sarcoma
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Perifosine in Multiple Myeloma (MM):
Synergistic Effect to Velcade®
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Velcade® (bortezomib)
caspase ↑
apoptosis
Perifosine blocks
Velcade®-activated Akt
Akt ↑
anti-apoptosis
Perifosine (μM)
24h
Perifosine (+) 5 μM
Perifosine (-)
Velcade®
(bortezomib)
0
5
10
20
0
p-Akt
5
10
20 nM
% control
120
100
80
60
40
Akt
20
p-ERK
0
ERK2
Reference: Hideshima et al. Blood 2006
0
2.5
5
0
5
7.5
Bortezomib (nM)
Perifosine in MM: Phase 1 and 2 results
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Perifosine + Velcade® +/- Dexamethasone in patients with
relapsed / refractory MM
Nb of
patients
ORR
Median TTP
Perifosine + Velcade®
+/- Dex
73
41%
6.4 months
Velcade® refractory
53
32%
5.7 months
Velcade® relapsed
20
65%
8.8 months
 Perifosine + Velcade® + Dex well tolerated and active in heavily pretreated and relapsed/refractory MM including Velcade® resistant patients
 Durable responses with an extended PFS
ASH 2009. Poster #1869
Perifosine in MM: Phase 3 Special Protocol
Assessment (SPA) with FDA
 Phase 3 multi-center randomized registration trial
comparing Perifosine + Velcade® + Dex vs. Velcade® +
Dex in previously treated Velcade® patients, has been
granted SPA and Fast-Track Review
 Patient enrollment initiated in December 2009 (n=400)
Inclusion Criteria
 Prior Velcade®-based treatment (relapsed)
 Prior Revlimid® and/or thalidomide treatment (relapsed or
refractory)
 1 – 4 prior lines of treatment (i.e. Dex, stem cell
transplant, and other approved/non-approved MM
treatment)
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Perifosine in MM: Phase 3 Special Protocol
Assessment (SPA) with FDA
Randomize
Velcade® 1.3 mg/m2 x 4d
Dex 20 mg x 8d
Placebo 50 mg daily
(n=200 patients)
Evaluate after 6 wks
If SD or > remain on tx
Velcade® 1.3 mg/m2 x 4d
Dex 20 mg x 8d
Perifosine 50 mg daily
(n=200 patients)
Progression
~ 265 events (PD/death)
Progression
Off Study
Off Study
Primary Endpoint
Progression Free Survival
Each cycle = 21 days
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Perifosine in MM: Large Market Opportunity
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 MM is the 2nd most prevalent blood cancer affecting 200,000
people worldwide and nearly 60,000 deaths/year
 Prevalence for
− U.S.: 15,000
− EU – G5: 16,000
− Japan: 3,500
 MM U.S. market: Over $3 billion in revenue in the coming
years
 MM Current therapies
− Velcade® (bortezomib – Millenium/Takeda): 2008 sales > $1 billion
− Revlimid® (lenalidomide – Celgene): 2009 sales > $1.7 billion
Source: Globocan 2002 & Frost and Sullivan
Perifosine in Metastatic Colon Cancer (MCC):
Synergistic Effect to Xeloda®
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+ Xeloda® (capecitabine)
Apoptosis
5-FU sensitive
Colon Cancer
+ Xeloda® (capecitabine)
NF-kB↑
5-FU resistant
Colon Cancer
Perifosine
AKT
NF-kB
NF-kB↓
IKK
Leleu et al., Blood, 2008.
Synergy 5-FU treatment and Akt
inhibition described in Kodach et
al., Carcinogenesis, 2006
Perifosine in MCC: Phase 2 Results
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38 patients were enrolled, of whom 35 were evaluable
Average number of prior therapies: 2
Xeloda® 825mg/m2 BID d1-14 and perifosine 50 mg daily
Group
n
CR
n (%)
PR
n (%)
SD > 12 wks
n (%)
CBR*
PD < 12 wks
n (%)
Xeloda® +
Perifosine
20
1 (5%)
3 (15%)
11 (55%)
15 (75%)
5 (25%)
Xeloda® +
Placebo
15
0
1 (7%)
5 (33%)
6 (40%)
9 (60%)
* CBR: Clinical Benefit Rate defined as patients on treatment > 12 weeks achieving stable disease
(SD) or better; p=0.036
Duration of response:
 Xeloda® + perifosine: CR – 34 months (ongoing); PR – 21, 19, 11 months
 Xeloda® + placebo: PR – 7 months
Reference: ASCO-GI Symposium 2010
Perifosine in MCC: Phase 2 Results
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Median Time to Progression (TTP) and Median Overall
Survival (OS) for all patients
Group
n
Xeloda® + Perifosine
20
Xeloda® + Placebo
15
Reference: ASCO-GI Symposium 2010
Median TTP
OS
28 weeks
18 months
[95% CI (12.0, 48.0)]
[95% CI (10.8,25.7]
11 weeks
11 months
[95% CI (9.0, 15.9)]
[95% CI (5.3,16.9)]
p = 0.0012
p = 0.0136
Perifosine in MCC: Phase 2 Results
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Subgroup of 5-FU Refractory Patients
A subgroup of 25 patients was evaluable for response
n
PR
n (%)
SD > 12 wks
n (%)
CBR*
PD < 12 wks
n (%)
Xeloda® +
Perifosine
14
1 (7%)
8 (57%)
9 (64%)
5 (36%)
Xeloda® +
Placebo
11
0
3 (27%)
3 (27%)
8 (73%)
Group
* CBR: Clinical Benefit Rate defined as patients on treatment > 12 weeks achieving stable disease
(SD) or better; p=0.066
Duration of response for PR: 19 months
Reference: ASCO-GI Symposium 2010
Perifosine in MCC: Phase 2 Results
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Median TTP – 5-FU Refractory Patients
p=0.0004
10 wks 18 wks
A
B
A = 11 patients [95% CI (6.6, 11.0)]
B = 14 patients [95% CI (12.0,36.0]
Reference: Bendell J. ASCO-GI Symposium 2010
Perifosine in MCC: Phase 2 Results
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Median OS – 5-FU Refractory Patients
p=0.0088
6.8 months
A
15.3 months
B
A = 11 patients [95% CI (4.8,11.7)]
B = 14 patients [95% CI (8.4,26.0]
Reference: Bendell J. ASCO-GI Symposium 2010
Perifosine in MCC: Phase 3 Special Protocol
Assessment (SPA) with FDA
 SPA granted by FDA in February 2010 for Phase 3 X-PECT
(Xeloda® + Perifosine Evaluation in Colorectal cancer
Treament) trial
 Study will be a randomized (1:1), double-blind trial
comparing the efficacy and safety of Xeloda® + perifosine
vs. Xeloda® + placebo
 Approximately 40-50 U.S. sites will participate in the study
 Study is expect to begin in Q2-2010 and enrollment is
expected to be completed in H2-2011
 Primary endpoint is overall survival and secondary
endpoints include ORR, PFS and safety
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Perifosine in MCC: Market Opportunity
 The fourth most commonly diagnosed cancer and second
leading cause of cancer-related deaths in the U.S.
− Prevalence of colon cancer for:
•
•
•
U.S.: 146,000
EU – G5: 110,000
Japan: 85,000
 About one third of patients already have metastatic
disease at diagnosis
 No new FDA approved drugs since 2006 – need for new
agents
 Current therapies for 1st and 2nd line of treatment [Xeloda®;
Avastin® ; Erbitux®] have overall sales of 4 billion US$
Source: Globocan 2002
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Perifosine in Advanced Metastatic Renal Cell
Carcinoma (RCC): Rationale
December 2009, The Journal of Urology, Camillo Porta and
Robert A. Figlin:
 “Cumulative evidence links PI3K/Akt alterations with RCC and
represents an ideal target for therapeutic intervention”
 “Only perifosine has already proven to be clinically active”
Reference: J. Urol 2009;182:2569-2577
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Perifosine in Advanced Metastatic RCC:
Phase 2 Study Design
Patients with advanced metastatic RCC
Progressing after either one prior therapy with a VEGF receptor inhibitor - Sutent® or
a VEGF receptor inhibitor and an mTOR inhibitor - Torisel®
Single agent - Perifosine 100 mg daily
Evaluate each 12 weeks
CR, PR,
Stable Disease
Progression
Continue
On Study
Off Study
Primary Endpoint
Each cycle = 21 days
Progression Free Survival
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Perifosine in Advanced Metastatic RCC:
Phase 2 Results - Monotherapy
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 50 patients were enrolled of whom 46 were evaluable
− 16 patients were refractory to both VEGF-R and mTOR
inhibitors
n
PR
n (%)
SD > 12wks
n (%)
Median PFS
(all patients)
Median PFS
(patients SD or >)
12.5 weeks
[95% CI (11.9, 19)]
33 weeks
[95% CI (24,60)]
Overall
survival
All patients (VEGF-R inhibitor)
46
5 (11%)
16 (35%)
Refractory patients (VEGF-R inhibitor + mTOR inhibitor)
16
1 (6%)
7 (44%)
16 weeks
[95% CI (11.7, 33.6)]
33.6 weeks
[95% CI (24, NR)]
Reference: ASCO 2009 and 8th International Kidney Cancer Symposium, Sept 2009
Not reached
(14/16 alive at
22+ months)
Perifosine Summary
 > 1,800 patients studied in Phase 1 and 2
− Single agent and combination
− No major haematological toxicity
 Phase 3 study in MM with SPA, Fast-Track review and
Orphan Drug status granted by FDA and EMA – Patient
enrollment initiated in Dec 2009 by our partner Keryx
 Phase 3 study in metastatic colon cancer with SPA
granted by the FDA – Patient enrollment will be initiated
in Q2-2010 by our partner Keryx
 Phase 2 studies ongoing in several other tumor types
including renal cell cancer, glioma, Waldenstrom’s
macroglobulinemia, and AML
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AEZS-108: Magic Bullet
Doxorubicin Targeted Conjugate
AEZS-108
conjugate
DOX
payload
Binding
Internalization
Nucleus
Migration
LHRH
targeting agent
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AEZS-108: Gynaecological Cancers
Phase 1 Study
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Dose Level
1
2
3
4
5
6
Dose [mg/m2]
10
20
40
80
160 (46*)
267 (76.8*)
Patients treated
1
1
1
1
6
7
Duration (Tx cycles)
2
2
2
2
2, 3, 5
6, 6, 6
1, 3, 4, 5
6, 6, 6
1 CR (6)**
1 CR (6)**
1 PR (6)**
2 SD
Response
2 SD

Duration
- Re-dosing at 3-week intervals (= 1 cycle)
- * equivalent doxorubicin dose
- ** treatment cycles (TX) completed

Response
- CR = complete response
- PR = partial response
- SD = stable disease
AEZS-108: Phase 2 Study in Endometrial
and Ovarian Cancer
 Design
− Conventional “Simon Design”
− Open-label study in patients with advanced or recurrent
endometrial and platinum-resistant ovarian cancer
− Two-stage design with up to 82 patients, 41 patients for each
indication
− Opening of stage 2 requires tumor remission in at least 2 of 21
evaluable patients in each indication
 Status
− Response criteria for opening stage 2 were met for both indications
− Enrollment for second stage completed for both indications
− Preliminary evaluation revealed that primary endpoint of 5 or
more responders was met for both indications
− Study ongoing for PFS and OS
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AEZS-112: Oral Tubulin and
Topoisomerase II Inhibitor
 Novel small molecule with oral capsule formulation
 Multiple modes of action:
− Inhibition of tubulin polymerization
− Inhibition of topoisomerase II
− Antiangiogenic properties
− Cell cycle arrest
 Strong in vivo activity and efficacy in multi-drug resistant (mdr) tumor
cell lines
 Phase 1 study (Dr Von Hoff, PI):
 42 patients treated
 12 patients with stable disease and time to failure of 5 – 14+ months
 Signs of activity in various indications including melanoma and cancers of
colon/rectum, lung, pancreas, prostate.
 Safety profile makes AEZS-112 an excellent candidate for drug
combinations
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AEZS-120 (Prostate cancer vaccine)
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 Oral live prostate cancer vaccine
 Basic feature: recombinant Salmonella strain with proprietary
secretion system of tumor antigen fused to
immunostimulatory factor
 Bacterial carrier acts as “intrinsic adjuvant” and has the
potential to activate components of the innate and adaptive
immune system
 Based on approved oral typhoid live vaccine Salmonella
typhi Ty21a, which has already been safely applied in > 250
Mio. doses
 Proof-of-Principle in animal model
 Off the shelf product, low cost of goods allows flexible pricing
 Platform technology
AEZS-130 (SolorelTM; macimorelin (INN))
A Growth Hormone (GH) Secretagogue Oral Ghrelin Mimetic
 Oral administration
 Excellent binding to human ghrelin receptor (agonist
mode)
 5 Phase 1 clinical trials completed to date with a total of
100 subjects treated
 Status: Phase 3 diagnostic of adult GH deficiency
 Orphan drug status for use as diagnostic test granted by
FDA
 Potential for Therapeutic indications given AEZS-130’s
GHS Activity and Ghrelin mimetic activity
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GH Concentration Following Oral Administration
of AEZS-130 in Healthy Volunteers
0.005 mg/kg AEZS-130
0.05 mg/kg AEZS-130
0.125 mg/kg AEZS-130
0.25 mg/kgAEZS-130
0.5 mg/kg AEZS-130
Placebo
GH concentration (ng/ml)
120
100
80
60
40
20
0
-20
0
60
120
time (min)
180
240
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AEZS-130 (SolorelTM): Diagnostic Test for
Adult GH Deficiency Preliminary Results
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PEAK GH RESPONSES TO
GHRH-ARGININE, SOLORELTM, AND ITT
SolorelTM
Better discrimination between adult GH deficiency patients and normal controls with
SolorelTM, oral solution, compared to the currently used test with GHRH-Arginine, i.v.
administration
Reference: 2009 ENDO meeting. G. Merriam et al. Poster P2-749
Potential Therapeutic Indications for a GHS
Ghrelin Mimetic Drug
 Ghrelin mimetic activity
− Cachexia associated with
cancer, COPD and AIDS
• U.S. prevalence for
cachexia:
 Cancer: 420 000
 COPD: 3 200 000
 AIDS: 315 000
− Post-operative ileus,
diabetic gastroparesis
Ref.: JE Morley et al. Am J clin Nutr 2006;83:735-743
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 GHS activity
− Hypo-pituitary
deficiency in adults
− Idiopathic short stature,
Turner’s syndrome,
chronic renal failure in
children
− Lipodystrophy
associated with HIV
treatment
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Financials
Selected Annual Financial Results
(in millions of US dollars)
Revenues
License fees
Sales and royalties
Other
Operating Expenses
Cost of sales, excluding D&A
R&D costs, net
SG&A expenses
D&A
Loss from operations
Other income (expenses)
Loss before income taxes
Income tax expense
Net loss
35
For the years ended
December 31, 2009
December 31, 2008
42.2
21.0
63.2
8.5
29.5
0.5
38.5
16.5
43.8
16.0
10.8
87.1
(23.9)
(0.8)
(24.7)
(24.7)
19.3
57.1
17.3
7.1
100.8
(62.3)
3.7
(58.6)
(1.2)
(59.8)
Cash Flows (Non-GAAP)
(in millions of US dollars)
(unaudited)
Cash, cash equivalents & s.-t. investments* –
beginning of the period
36
For the year
ended
December 31,
For the year
ended
December 31,
2009
2008
49.7
41.4
(24.1)
(1.3)
Net cash provided by (used in) financing activities
14.2
(1.2)
Net cash provided by (used in) investing activities
(0.2)
13.6
Exchange rate fluctuation impact and other
(1.5)
(2.8)
(11.6)
(8.3)
38.1
49.7
Net cash used in operating activities
Cash, cash equivalents & s.-t. investments – end of
the period
* Excluding restricted cash (2009 only); no short-term investments as at December 31, 2009.
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Goals for 2010
2010 Goals
Perifosine: Oral Akt inhibitor
 Our partner, Keryx, to progress patient enrollment for the
randomized Phase 3 placebo-controlled registration study in
multiple myeloma (MM) according to the SPA agreed
protocol with FDA
 Keryx to initiate a Phase 3 trial in Metastatic Colon Cancer in
Q2-2010 according to the SPA protocol with the FDA
 Report results for ongoing Phase 2 studies in MM, Metastatic
Colon Cancer, Pediatric Solid Tumors and other cancers
 AEZS to update development and registration strategy for
ex-North American territories, including Europe and Asia
38
2010 Goals
AEZS-108: Doxorubicin-targeted conjugate
 Report final results from Phase 2 study in advanced
ovarian and advanced endometrial cancer
 Initiation of additional clinical studies in advanced ovarian
or advanced endometrial cancer
 Initiation of one or more Phase 1/2 trials in other LHRH
expressing cancer types
39
2010 Goals
AEZS-130 (SolorelTM): Oral ghrelin agonist
 Completion of Phase 3 study for diagnostic test for adult
growth hormone deficiency (GHD)
 Filing of an NDA in U.S. as diagnostic test for adult GHD
pending successful completion of Phase 3 study
 Initiation of clinical program in pediatric GHD
 Update development and registration strategy
− “Rest of world” as diagnostic test in adult and pediatric GHD
 Explore potential for therapeutic use
40