Aeterna Zentaris

WAITING FOR SUCCESS...

2

WHEN?

33

1990

Aeterna Laboratories

formation

4

Commercial division: cosmetics and nutritional supplement

Aim: developing a medicine against cancer

AETERNA FORMATION

90/09/12: creation of Aeterna Laboratories by Eric and Luc Dupont

Commercial earnings reinvest in cancer R&D

Financial need: creation of Atrium Biotechnologies

Paul Burroughs, Communication Director, Aeterna Zentaris Inc.

5

SHARK CARTILAGE AND CANCERS

Cancerous cell

Anti-collagenase activities: MMP inhibitors

Fractions of cartilage: anti-angiogenesis power

•Adequate extraction of the anti-angiogenic molecules•Preservation of biological activities during extraction and storage

Problem: quality of the powder composition

Shark cartilage extracts as anti-angiogenic agents: smart drinks or bitter pills? D. Gingras, A. Renaud, N. Mousseau, R. B´eliveau, Cancer and Metastasis Reviews 19: 83–86, 2000.

Black/Common Spiny Dog Fish

6

AE941

Shark cartilage extracts as anti-angiogenic agents: smart drinks or bitter pills? D. Gingras, A. Renaud, N. Mousseau, R. B´eliveau, Cancer and Metastasis Reviews 19: 83–86, 2000.

Effect of Æ-941 on embryonic neovascularization.Chick embryo

•Water-soluble extract•Concentrated in biologically-relevant molecules

New entity

7

AE941

Oncology

Dermatology

Ophthalmology

Rheumatology

Neovastat®

Psovascar®

Neoretna®

Arthrovas®

Discontinued

Renal and non-small cell lung cancer development

8

AE941

Orphan drug status in renal cancer (FDA)

October 2002

Phase III study for metastatic renal cancer doesn’t achieve its goal

September 2003

9

AE941

Clinical development stopped in renal cancer

December 2003

Clinical development stopped in non-small cells lung cancer

February 2006

Chemoradiotherapy With or Without AE-941 in Stage III Non–Small Cell Lung Cancer: A Randomized Phase III Trial, Charles Lu and Al, JNCI, 2010 102 (12)

1010

1990


formation

2002

Zentaris AG acquisition

11

Marketing alliances and strategic partnerships: •Serono•Solvay•Baxter

ZENTARIS AG

Zentaris AG

Degussa AG Asta-Medica GmbH

New opportunities

Aeterna acquires German biopharmaceutical Zentaris from Degussa, PR Newswire

12

ZENTARIS AG

•Oncology:o6 products in clinical trials (phases I to III)o2 products in preclinical phase

New portfolio

•Endocrinology:o1 product approved and commercializedo1 product in clinical trialso2 products in preclinical phase

1313

1990


formation

2002

Zentaris AG acquisition

March 2003

Aeterna GmbH & Zentaris AG

merger

May 2004

New name: Aeterna Zentaris Inc.

March 2004

Atrium Biotechnologies Inc. acquired Pure Encapsulations Inc.

Aeterna Zentaris, Thomson Reuters Pharma ™company report

14

January 2005

Atrium Biotechnologies Inc. acquires

Multichem Inc.

Echelon Biosciences acquisition


15

AEZS IN 2005...

16

THE END OF ATRIUM

20062007

Atrium voting shares distribution

January 2005

Atrium Biotechnologies Inc. acquired

Multichem Inc.



17

3,485 million voting shares $47 million (24% of $14,12 each share the company’s ownership)

SHARES DISTRIBUTION

October 2006: Beginning of Atrium shares distribution


Last 11 million sharesShareholders would receive 0.2079 of an Atrium share for each Aeterna share

January 2007: End of Atrium shares distribution

18

November 2007

Echelon Biosciences sale

20062007

Atrium voting shares distribution

January 2005

Atrium Biotechnologies Inc. acquired

Multichem Inc.


19

WHERE?

20

AEZS AROUND THE WORLD

Aeterna Zentaris Inc.Canada

Aeterna Zentaris GmbHGermany

Zentaris IVF GmbHGermany

Aeterna Zentaris Inc.New Jersey, USA

10

10

80

Aeterna Zentaris ANNUAL INFORMATION FORM ON FORM 20-F 2010

21

WHAT?

22

PRODUCTS

Product development

Therapeutic areas

Oncology

Own product discovery unit

Colorectal cancer

Multiple Myeloma

Endometrial cancer

Ovarian cancer

Prostate cancer

Bladder cancer

Endocrinology

Adult Growth Hormone Deficiency

In vitro fertilization

23

PIPELINE

Investor Presentation, February 14th, 2012, www.aezsinc.com

24

World: Merck Serono

JP: Shionogi

JP: Nippon Kayaku

EU: 1999

US: 2001

JP: 2006

CETRORELIX - CETROTIDE®

Approval

Marketed

www.aezsinc.com, Products in the market, Cetrotide®

> 90 countries

http://www.aezsinc.com/

25

CETRORELIX - CETROTIDE®

MarketedIn Vitro fertilization

LHRH antagonist

Pr Andrew Schally

Dose-dependent action

DevelopmentBenign Prostatic Hyperplasia

Endometriosis

Uterine myomawww.aezsinc.com, Products in the market, Cetrotide®


26

HORMONAL CYCLE

Hypothalamus

Hypophysis

LH-RH

LH & FSH

Ovarian

Estrogens

-

Follicular phase

14 days

http://fr.wikipedia.org/wiki/Am%C3%A9norrh%C3%A9e

27

HORMONAL CYCLE

Hypothalamus

Hypophysis

LH-RH

LH & FSH

Ovarian

Estrogens

+

Ovulation

Ovulation

14 days 14 days


28

+

DEFICIENT HORMONAL CYCLE

LH surge too soon

Hypothalamus

Hypophysis

LH-RH

LH & FSH

Ovarian

Estrogens

Follicular phase

-


-

29

CETROTIDE® IN THE TYPICAL OVARIAN STIMULATION CYCLE

Start of stimulation

cycle

Possibility of LH surge

begin

Eggs nearly mature

Eggs retrieved for fertilization

with sperm

Embryos transferred (3 to 5 days after

egg retrieval)

FSH or hMG (Gonal-F®)

Stimulates growth of eggs

Cetrotide®

Prevents early release of

eggshCG

Induces maturation of

eggs

www.aezsinc.com

302006 2007 2008 2009 2010

0

20,000

40,000

60,000

80,000R&D Sales

Thou

sand

s $ -56.2%

-54.7%

Association with Sanofi

CETROTIDE® IN BHP

March 2009

Study results: primary endpoints not matchedDecember, 7th 2009

End of the association Discontinuation of Cetrorelix in BHP December, 18th 2009

www.aezs.com Financial report 2010 and 2008

http://www.aezs.com/

31

PIPELINE


32

PERIFOSINE

Oral anticancer treatment

PI3K (phosphoinositide 3-kinase) pathway

Inhibition of Akt activation

Alkylphosphocholine

Induction of apoptose

www.aezs.com ANNUAL INFORMATION FORM ON FORM 20-F 2010

33

THE PI3K PATHWAY

+ Perifosine

34

FDA : Orphan drug

PERIFOSINE

Multiple Myeloma

Perifosine Bortezomib Dexamethasone

Perifosine Lenalidomid Dexamethasone

Phase 3

September 2009

December 2009 FDA : Fast Track designation

March 2010 EMA : Orphan drug


35

PERIFOSINE

Colon cancer

Perifosine Capecitabine

Phase 3

April 2010 FDA : Fast Track designation

PATENT

E

D

July 2011 EPO : Patent for the association

Until July 28th, 2023

Aeterna Zentaris ANNUAL INFORMATION FORM ON FORM 20-F 2010Press release July 12th, 2011

36

PERIFOSINE

Colon cancer

Perifosine Capecitabine

Phase 3

April 2010 FDA : Fast Track designation

PATENT

E

D

July 2011 EPO : Patent for the association

Until July 28th, 2023


Phase 2 : Time to Progression and Overall Survival

37

PERIFOSINE

Waldenstrom’s Macroglobulinemia

Renal cell carcinoma

Phase 2

Sarcoma

Gliomas

Neuroblastoma

Phase 1

Leukaemia

Non-Small Cells Lung Cancer+ Radiation therapy


38

DEVELOPMENT PARTNERSHIP

NIH/NCI : Cooperative Research and Development AgreementMay 2000

Access Oncology, Inc./Keryx : Cooperation and license agreement for the United States, Canada and Mexico

September 2002


39

ACCESS ONCOLOGY, INC/KERYX

Cooperation and license agreement for the United States, Canada and Mexico

Free access to all data from Keryx and its partner’s studies

Milestone payments

Scale-up royalties to be paid on future net sales of Perifosine

Clinical Development


40




September 2002


Handok : Agreement to out-license the rights of Perifosine in South Korea

April 2009Yakult : development, manufacture and commercialization of

Perifosine in Japan

March 2011

41

YAKULT

Development, manufacture and commercialization of Perifosine in all human

uses, excluding leishmaniasis in Japan

Initial up-front payment of €6 million ($8.3 million)

Milestone payments : up to €44 million ($60.9 million)

Royalties on future net sales of Perifosine in the Japanese market

Development, Manufacture, Commercialization in Japan


42




September 2002

Aeterna Zentaris ANNUAL INFORMATION FORM ON FORM 20-F 2010Aeterba Zentaris Press Release – November 23rd, 2011

Handok : Agreement to out-license the rights of Perifosine in South Korea

April 2009Yakult : development, manufacture and commercialization of

Perifosine in Japan

March 2011

November 2011

Hikma pharmaceuticals : Commercialization and license agreement for the MENA region

43

HIKMA

Commercialization and license agreement for the MENA (Middle East and North Africa)

region

Initial up-front payment

Milestone payments : up to $2 million

Supply perifosine to Hikma Pharmaceuticals on a cost-plus-

basis

Registration and marketing of perifosine

Aeterba Zentaris Press Release – November 23rd, 2011

Leading drug company in the MENA region

Royalties on future net sales of perifosine in the MENA region

44

POTENTIAL MARKET VOLUME


45

PIPELINE


46

AEZS-108


47

AEZS-108

Reproductive Tissue

Hypophysis

Cancer Tissue(e.g. breast, endometrial, ovarian,

prostate and bladder cancer)LHRH receptor

AEZS-108

↑ Efficacy ↓ Side-Effects

Consequence for the cytotoxic agent :

Healthy Tissue


48

AEZS-108

Refractory Ovarian Cancer

Phase 2

Recurrent Endometrial Cancer

Positive efficacy and safety data

Phase 1

Refractory Prostate Cancer

Bladder Cancer

JANUARY 5, 2012 : COLLABORATION WITH

VENTANA MEDICAL

Positive efficacy and safety data


49

PIPELINE


50

AEZS-112

Phase 1

Topoisomerase II inhibition Tubulin polymerisation inhibition

Two Mecanisms of action

Advanced solid tumors

Colon/rectum

Pancreas

Lung Trachea

Prostate Thyroide

No clinically relevant drug-related adverse events www.aezsinc.com

51

PIPELINE


52

MACIMORELIN SOLOREL®

Diagnostic test for Adult Growth

Hormone Deficiencies

Low energy levels

Decreased strength and exercise tolerance

Increased weight or difficulty losing weight

Emotional changes

AnxietyImpaired sleep

www.aezsinc.com

53


Ghrelin agonist



Phase 3

www.aezs.com

54


Hypothalamus

Hypophysis

GH-RH

GH

Ghrelin agonist

www.aezs.com

55


Secretion of growth hormone (GH)

No secretion of growth hormone (GH)

No growth hormonedeficiencies

Growth hormonedeficiencies

Ghrelin agonist



Phase 3

www.aezsinc.com

56

AEZS-130

Tumor induced cachexia and others

Ghrelin agonist

Phase 1

www.aezsinc.com

57

AEZS-130

Hypothalamus

Hypophysis

Metabolic activationTissue growth

MusclesBones

GH-RH

GH

IGF I/II

Liver

Ghrelin agonist

www.aezsinc.com

58

AEZS-130

Tumor induced cachexia and others

Ghrelin agonist

↓ loss of weight ↓ muscle atrophy ↓ fatigue ↓ weakness ↓ loss of appetite

Phase 1

www.azesinc.com

59

AND WHAT ABOUT THE MONEY?

60

THE « AFTER ATRIUM »

http://www.nasdaq.com/symbol/aezs/interactive-chart

Sanofi partnership

Studies good results announcement

2006 2007 2008 2009 201050000000550000006000000065000000700000007500000080000000

Number of shares

Mill

ion

61

FINANCIAL DIFFICULTIES

2006 2007 2008 2009 2010

-60,000

-40,000

-20,000

0

20,000

40,000

Net operating incomes

Thou

sand

s $

2007 2008 2009 20100

10000

20000

30000

40000

50000

60000

70000

12517

6469757768

50648

Long-term liabilities

Audited Annual Financial Statements 2010 and 2008

62

THE FUTURE (S)…

63

NOVARTIS

Exjade®

Femara®

Gleevec®

Tasigna®

Afinitor®

Zometa®Sales 10 b$

www.novartis.com

64

NOVARTIS

Pipeline in 2011

www.novartis.com Annual Report 2011

http://www.novartis.com/

65

ROCHE

Sales by therapeutic areaOncology leader

MabThera®

Xeloda®

Avastin®

Tarceva®

Herceptin®

Phase III and registration

Roche in Brief 2011 by Roche

66

ROCHE

Avastin®

Herceptin®

Tarceva®

Rituxan®

Protropin®

Nutropin®

Oncology leader

MabThera®

Xeloda®

Avastin®

Tarceva®

Herceptin®

www.gene.com

67

Aezs-108 (diagnosis companion test)

Oncology leader

ROCHE

Protropin®

Nutropin®

MabThera®

Xeloda®

Avastin®

Tarceva®

Herceptin®

www.aezsinc.com Press Release January, 5th 2012


68

O

W

T

DebtsFinancial dependence1 product marketedDependent on third partiesFailure in Phase 3 or SAE : detrimentalLow-value shares : tender offer?Purchase? Bankrupt?

2 products in phase 3Oncology : growing

marketCompanion test

Fast Track processes2 NDA for 2012

Orphan Drugs

Focused R&DPromising pipeline

Focused on 2 areasMultiple indications

Cetrotide® sales better than expected

S

69

THANKS FOR YOUR ATTENTION

Health & Medicine

Aeterna Zentaris