Biosimilars in an Individualized Therapeutics World- The Challenge in Oncology

3rd DVFA-Life Science ConferenceNeue Börse, Frankfurt am Main

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About Ganymed

ScientificFounders

Ugur Sahin, Christoph Huber, Özlem Türeci (III. Dept. of Medicine, Mainz)Hans Hengartner, Rolf Zinkernagel (Nobel Laureate, Exp. Immunology, Zurich)

Management Özlem Türeci, Ugur Sahin, Dirk Sebastian, Rainer Wessel

MajorMilestones

Q3/2001 Foundation in Mainz2002-2007 €52.5 Mio equity raised in three financing roundsQ3/2008 ATS (Drs Strüngmann) acquire majority & €65 Mio equity raisedQ2/2010 Finalization of Claudiximab Clinical Phase I (gastro-esophag. cancer)Q3/2010 Initiation of Claudiximab Clinical Phase IIa (gastro-esophag. Cancer)Q3/2010 Lead decision for GT512iMAB (Ovarian Cancer)

Current Staff 71 FTE

Focus: Development of effective antibody therapeutics against solid cancers based on novel highly tumor specific targets

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New Rules?

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The Human Genome Project:Genetics is pushing fast forward

"Science is essentially a cultural activity. It generates pure knowledge about ourselves and about the universe we live in, knowledge that continually reshapes our thinking" [1] [John Sulston]

In 1953 James Watson and Francis Crick discovered the structure of DNA -the code of instructions for all life on earth...

...in 2003 - just 50 years later - humankind had developed and exploited the technology, the computing capability and the financial and social impetus to record one whole human DNA sequence: some 3 billion letters of genetic code.Source: http://www.sanger.ac.uk/about/history/hgp/ April 26, 2010

What will 2050 look like?

It will be an individualized therapy world.

Biomarker are the basis for individualized medicine

Different fields of use

•Diagnostic

•Prognostic

•Predictive

•Target structures for Therapeutics− Small molecules− Antibodies− Vaccines− siRNA− RNA & DNA− Other

In oncology individualized therapies will become standard

Combination of small molecules and antibodies are already reality

The coming decades will see the rise of Vaccines

Other therapeutic classes will follow

As a result we will have a growing individualized cancer therapeutics toolkit at our disposal

A look at the regulatory side

EMA has already established or is developing guidelines on “Similar Biological Medicinal Products“, e.g.•”Guideline On Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins As Active Substance: Non-Clinical And Clinical Issues“ (June 1, 2006)•Guidelines for substance classes: “Guideline On Production And Quality Control Of Monoclonal Antibodies And Related Substances”•Draft “Concept Paper On The Development Of A Guideline On Similar Biological Medicinal Products Containing Monoclonal Antibodies”•Guidelines for specific “Biosimilar Products” like EPO, G-CSF and Interferons are in place, further are in development

FDA has not yet introduced guidelines for the regulation of „Similar Biological Medicinal Products“

However, it is likely that the FDA will adopt the EMA guidelines, more or less.

Outlook

Experience with „Similar Biological Medicinal Products“ is rapidly growing at regulatory agencies and within the pharmaceutical industry

Guided by this experience and driven by political pressure, further guidelines will be implemented, which will facilitate the introduction of further Biosimilars.

It is likely that in the future, in case of use of the same expression system, for approval it will be sufficient to demonstrate comparability based on•Biochemical analysis, and•Acute Tox, and PK in suitable animal models.

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Product Name & Type

OriginatorCompany Indication Launch

YearMarketingCompany

Sales 2009[billion €]

Avastin®

(Bevacizumab)humanized

GenentechAdvanced colorectal,

breast, lung and kidney cancer

2004 Roche4.2 (21%)

CHF 6.2

Rituxan®

(Rituximab)chimeric

IDECGenentech

Non-Hodgkin's Lymphoma

(NHL), Leukemia and RA

1997 Roche 4.1 (+6%)CHF 6.1

Herceptin®

(Trastuzumab)humanized

Genentech

Her2 positive metastatic breast cancer and other

approved indications

1998 Roche 3.6 (+8%)CHF 5.3

Erbitux®

(Cetuximab)chimeric

ImClone

Metastatic colorectal

carcinoma and other approved

indications

2003 BMSEli Lilly

Merck Serono

1.2 (~ +10%)

$683(-9%)$92.5 (n.a.)

€697(+23%)

Blockbuster Cancer Antibodies

10

0

10

20

30

40

50

60

70

80

90

100

0 5 10 15 20 25

Month after Enrollment

Pro

gres

sion

-free

Sur

viva

l (%

)

Herceptin® in breast cancer therapy

Approximately 20% of breast cancer patients over express the Herceptin® target (Her2/neu)

SLAMON et al. New England Journal Medicine 2001

Served Medical Need

Chemotherapy + Herceptin®

ChemotherapyAlone

Patients with metastatic breast cancer

RemainingMedical Need

P<0.001

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“Get the target right, first”

Ganymed’s ideal target specificity

Gut

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in

Kidn

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Stom

ach

Lung

Hear

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vary

Blad

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Brea

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ance

r 1Br

east

Can

cer 2

Brea

st C

ance

r 3Br

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Can

cer 4

Brea

st C

ance

r 5

Normal Tissue Cancer

GanymedGT43

Her2/neu(Target of Herceptin®)

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Ganymed’s pan cancer target pipeline

GC182 (CLDN18.2)! Gastric differentiation gene

• 70% of gastric cancers• 50% of pancreatic cancers• 30% of esophageal cancers• 25% of NSCLC

GT43! Tumor specific phosphatase

• 50% of melanomas• 40% of prostate cancers• 30% of lung cancers• 20% of breast cancers

GT352! Colorectal differentiation gene

• 90% of colorectal cancers

GT507! Cancer/germline gene

• 90% of prostate cancers

GT468! Placental gene

• 80% of breast cancers• 60% of NSCL cancers• 20% of ovarian cancers

Solid IP position •Freedom to Operate, and •Target & Product Protection 34 issued patents &157 applications

GT512• 70% of ovarian cancers• 50% of NSCL cancers

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Learning from successful targets: CD20The target of Rituximab (Rituxan®, MabThera®)

Molecular target-immanent features contributing to clinical success of CD20 mAb therapies

Potent cytotoxic effectsTarget topology plays major role, in particular aggregation of CD20 in lipid rafts and vicinity of mAB epitope to cell membrane

Optimal therapeutic windowExpression restricted to mature B-cells, sustained in B-cell malignancies, but not shared by the stem cell precursor of the B-cell lineage

... and others

1 2

3

N

C

Cell surface

Abstract such features and compile them into a query tool allowing mining of sequence databases (In Silico Cloning)

Apply bioinformatical tool for a search of cell surface structures expressed in solid cancers (i.e. gastric cancer)

Commercially validated public domain target

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Characteristics of iMAB362 target CLDN18.2

! Discovered by In Silico cloning for CD20 analogous molecules

! Identical to CLDN18.2, a member of the claudin super family of tight junction components

! 24 kDa protein with four trans membrane domains and 2 short extra cellular loops (51aa, 24aa)

! Forms aggregates on the cell surface

Cell surface

1 2

3

Stomach cancer cell linewith endogenous CLDN18.2 expression,staining with rabbit anti-CLDN18.2

N

CSNU16

Ganymed proprietary target

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No expression of iMAB362 target transcript or protein in any tox relevant human tissue

CLDN18.2 prevalence in solid cancers

Normal tissues withCLDN18.2 expression

Normal tissues free ofCLDN18.2 expression

Gastric cancer (~70%)Pancreatic cancer (~50%)Esophageal cancer (~30%) Lung cancer (~25%)

Stomach EsophagusSmall intestineColonLiverPancreasGall bladderBreastOvaryKidneyTestisCervixPlacentaUterusBladder/UrotheliumLungHeartEndotheliaSkinSkeletal muscleThyroid

ProstateEndometriumTotal BrainCerebral cortexCerebellumNucleus caudatusHippocampusPonsPituitary glandRetinaGangliaBone MarrowSpleenTonsilsB lymphocytesCD4+ T lymphocytesCD8+ T lymphocytesGranulocytesDendritcs cellsAdrenal glandSalivary gland

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Strong presence of iMAB362 target in primary & metastatic cancer

Unselected specimen from primary gastric cancer and gastric cancer metastasis (Krukenberg tumors & lymph node metastases) were stained with a CLDN18.2 specific rabbit antiserum. Immunohistochemistry as well as evaluation of staining intensity and proportion of tumor cells showing a plasma membrane staining was performed by an expert clinical pathologists.

0

20

40

60

80

100

-0,5 0 0,5 1 1,5 2 2,5 3 3,5neg +1 +2 +3Staining Intensity

% c

ells

with

mem

bran

e st

aini

ng

Primary gastric cancer

0

20

40

60

80

100

-0,5 0 0,5 1 1,5 2 2,5 3 3,5neg +1 +2 +3Staining Intensity

% c

ells

with

mem

bran

e st

aini

ng

distant metastasis lymph node metastasis

Gastric cancer metastases

In both primary and metastatic gastric cancers ~70% of patients have a staining intensity of at least +2 in at least 70% of cells

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Mode of Action of iMAB362

Tumor Cell

2. CDC1. Inhibition of Target Function

Fc

FcR+Effector

cell

3. ADCC

Claudin18.2

4. Apoptosis induction

Cell Death

Growth Inhibition Tumor

Killing

CDC: Complement Dependent CytotoxicityADCC: Antibody Dependent Cellular Cytotoxicity

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iMAB362 (Claudiximab) mode of action is strictly CLDN18.2 target dependent

Specific Binding Growth Inhibition

CDC ADCC

Apoptosis

NUG-C4

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28 day repeated dose toxicity study in cynomolgus monkeys with three iMAB362 dose levels (10, 30, 100 mg antibody per kg body weight) showed:

• No iMAB362 related local or systemic signs of toxicity• No clinical symptoms• No mortalities • No changes in behavior and health of animals• No tissue destruction (morphological and histological post

mortem analysis of all organs including stomach)

28 day toxicity study with iMAB362 in Cynomolgus showed no apparent toxicity

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• Multicenter Clinical Phase I study with iMAB362 in gastro-esophageal cancer patients performed in Europe

• Single dose escalation, 15 patients in 5 cohorts, 3 patients per cohort:• 33mg/m2

• 100mg/m2

• 300mg/m2

• 600mg/m2

• 1g/m2

• No related Serious Adverse Events

• Multicenter Clinical Phase IIa study in gastro-esophageal cancer patients to be initiated in Europe in third quarter 2010

iMAB362 Clinical Phase I study in patients showed no related Serious Adverse Events

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iMAB362 project

Epitope Selection,Hybridoma Gen., Lead Selection & Cell Line Dev.

cGMP Manufact.* Pre-clinic & Regulatory

Q2/2007

Clinical Phase IGastro-EsophagealCarcinoma

Q2/2009Q2/2004

Clinical Phase IIaGastro-EsophagealCarcinoma

Q3/2010

* State of the Art robust high yield CHO clone (Lonza GS) in place (>3g/l)

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• iMAB362 follows the target and mechanistic concept of Rituximab

• iMAB362 has similar characteristics like Rituximab

• iMAB362 targets 70% gastric, 50% pancreatic, 30% esophageal, and 25% NCSL cancers, Rituximab targets B-cell lymphomas and RA

• iMAB362 target is proprietary to GANYMED, CD20 is public domain

iMAB362: Following the success of Rituximab

" Exclusivity in large Blockbuster Markets up to 2025

1st line of defenseTarget Claims

2nd line of defense Product Claims

3rd line of defenseOrphan Drug Status

IP-Strategy with several lines of defense

Multiple patent families

iMAB362

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Ganymed’s pan cancer target pipeline

GT43! Tumor specific phosphatase

• 50% of melanomas• 40% of prostate cancers• 30% of lung cancers• 20% of breast cancers

GT352! Colorectal differentiation gene

• 90% of colorectal cancers

GT507! Cancer/germline gene

• 90% of prostate cancers

GT468! Placental gene

• 80% of breast cancers• 60% of NSCL cancers• 20% of ovarian cancers

GT512• 70% of ovarian cancers• 50% of NSCL cancers

GC182 (CLDN18.2)! Gastric differentiation gene

• 70% of gastric cancers• 50% of pancreatic cancers• 30% of esophageal cancers• 25% of NSCLC

Solid IP position •Freedom to Operate, and •Target & Product Protection 34 issued patents &157 applications

Government & Service Companies

Development of solutions for the approval and marketing of individualized therapeutics

Clinical CenterClinical Center

Translatory Centre(TRON)

Translatory Centre(TRON)

Regulatory WorkgroupRegulatory Workgroup

Biomarker CenterBiomarker Center

CI3 Cooperation andIntegration Structure

Products of different commercial maturity

Academic Innovations

Individualized Immune Therapeutics

Developers of Therapeutics

Biomarker Development

Cluster for Individualized ImmuneIntervention

The „Mainzer Modell*“

* Transkript 10/2009

Individualized Medicine requires new positioning of all players of the health system

Health

InsurancePharma &

Service

Companies

Physicians & Hospitals

Patients

Basic &

Clinical

ResearchBasic &

Clinical

Research

Pharma & Service

Companies

Basic & Clinical

Research

Basic & Clinical

Research Translation

Individualized Medicine requires new positioning of all players of the health system

Pharma & Service

Companies

Physicians & HospitalsBasic &

Clinical Research

Basic & Clinical

Research Translation

Individualized Medicine requires new positioning of all players of the health system

Health Insurance

Pharma & Service

Companies

Physicians & HospitalsBasic &

Clinical Research

Basic & Clinical

Research Translation

Individualized Medicine requires new positioning of all players of the health system

Health Insurance

Pharma & Service

Companies

Physicians & HospitalsBasic &

Clinical Research

Basic & Clinical

Research Translation

Individualized Medicine requires new positioning of all players of the health system

Health Insurance

Pharma & Service

Companies

Physicians & Hospitals

Patients

Basic & Clinical

Research

Basic & Clinical

Research Translation

Individualized Medicine requires new positioning of all players of the health system

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New Rules and Players!

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Disclaimer

This presentation is not and under no circumstances to be construed as a solicitation, offer, or recommendation, to buy or sell securities issued by GANYMED Pharmaceuticals AG. GANYMED Pharmaceuticals AG makes no representation (either express or implied) that the information and opinions expressed in this presentation are accurate, complete or up to date. GANYMED Pharmaceuticals AG disclaims, without limitation, all liability for any loss or damage of any kind, including any direct, indirect or consequential damages, which might be incurred in connection with the information contained in this presentation. This presentation expressly or implicitly contains certain forward-looking statements concerning GANYMED Pharmaceuticals AG and its business. Certain of these forward-looking statements can be identified by the use of forward-looking terminology or by discussions of strategy, plans or intentions. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of GANYMED Pharmaceuticals AG to be materially different from any expected results, performance or achievements expressed or implied by such forward-looking statements. There can be no guarantee that any of the research and/or development projects described will succeed or that any new products or indications will be brought to market. Similarly, there can be no guarantee that GANYMED Pharmaceuticals AG or any future product or indication will achieve any particular level of revenue. In particular, management’s expectations could be affected by, among other things, uncertainties involved in the development of new pharmaceutical products, including unexpected preclinical and clinical trial results; unexpected regulatory actions or delays or government regulation generally; the Company’s ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry, and general public pricing and other political pressures. GANYMED Pharmaceuticals AG is providing the information in this new release as of the date of the publication, and does not undertake any obligation to update any forward-looking statements contained herein as a result of new information, future events or otherwise.