Protagen AG

Otto-Hahn-Str. 15

D-44227 Dortmund

www.protagen.com

The AutoImmuneDx Company

CONFIDENTIAL

European Business Development Conference Düsseldorf , September 2013

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PROTAGEN Introduction & SeroTag® Autoantibody Profiling

PROTAGEN Experience, Expertise & Product Portfolio

Case Study : Response Prediction in early RA

Investment Case

1

2

3

4

Agenda

Protagen AG – Key Facts

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Human Protein Library

Protagen HQ, Germany

1000 m² lab facilities

Set-up:

Experienced management team

ISO 9001/2008 certified

Expertise

Unique, exploratory SeroTag® approach

for Dx/CDx development

Focus on autoimmune diseases

Excellent IP position

Financial status

Privately held

Committed, long-standing investors

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Biggest Expression

Library

High Throughput

Measurement

Leading

Analysis

Team

Impeccable

Quality

The SeroTag® - Process: Success Factors

Unique, fully integrated,

exploratory Approach

One of biggest protein libraries

Established high throughput

technology - Luminex®

Industry Leading Biostatistical

Analysis Team

Marker developed in parallel to

compound – We won’t fail you!

Applicable to Dx & CDx

development

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SeroTag® technology employs autoantibodies as biomarkers

CONFIDENTIAL

hPEX®

Antigen Expression Library

• 180,000 clones

• 14,000 genes

• >7,000 proteins

SeroTag®

Bead-Based Arrays

• Multiplex analysis of up to 500 proteins in 1 bead set

Data Mining & Statistics

• Single markers and combinations of markers

• Criteria: AUC, p-value, sensitivity, specificity

SeroTag® - The Technology

Business Model

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hPEX® & SeroTag®

Technology

SLE

IVD

RA AID

Value

Generation

IP Data

$

New Indications CDx

2017 +

SLE AID

Pharma

Collaborations

MS RA

IP Data

New Indications

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PROTAGEN Introduction & SeroTag® Autoantibody Profiling

PROTAGEN Experience, Expertise & Product Portfolio

Case Study : Response Prediction in early RA

Investment Case

1

2

3

4

Agenda

Drug Development for Autoimmune Therapy

An endeavour with many challenges

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Sales of 9.3 billion US$ in 2012

Average non-responder rate in Autoimmune Disease Drug Therapy ~ 50%

PROTAGEN

Increases your chances!

Experience & Expertise

Core Area: Rheumatology & Immunology

-9-

RA; 75 SLE;

130

Healthy; 250

Early Arthritis;

751

PSS; 100

AS; 82

Early RA Humira/

MTX Study;

349

Why Immunology/

Autoimmune-Diseases?

Area of high unmet medical

need

Often lack of stratification

biomarkers for new medicines

Autoantibodies well established

in most indications

Broad IP base on markers,

autoantigens and autoantibodies

Own Dx/CDx development

CONFIDENTIAL

RA in vitro Diagnostic Assays – Current Status

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• Established IVD market in RA

• With room for improvement of sensitivity

• And a clear need for additional IVDs, in particular for seronegative

patients

RF IgM RF IgA Anti- CCP2 Anti- MCV

RA sensitivity 60-80% 44% 39-94% 69.5-82%

RA specificity 80-95% 84% 81-100% 90.3-98%

Early RA sensitivity 15-30% 29-39% 25-58% 57-71%

Disease activity correlation ? yes no yes

Correlation to outcome yes yes yes Yes

Association to extra-cellular

manifestation yes yes yes unkonwn

RF: rheumatoid factor

Egerer et al; 2009 (Dtsch. Ärzteblatt)

PROTAGEN Market Overview

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Market

Importance

Market Size

≈

≈

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PROTAGEN Introduction & SeroTag® Autoantibody Profiling

PROTAGEN Experience, Expertise & Product Portfolio

Case Study : Response Prediction in early RA

Investment Case

1

2

3

4

Agenda

Disease

Average % of

non-

Responders

Author Citation

Rheumatoid Arthritis (ACR20) 28 - 58 Craig Beavers et al.Orthopedics

January 2010 - Volume 33 · Issue 1

Ankylosing spondylitis (ASAS

20)40 C McLeod et al. Health Technol Assess 2007;11:1–158

Psoriatic Arthritis (MEASE

2004, 24weeks, PsARC and

ARC50)

30 - 63 M Rodgers et. All Health Technology Assessment 2011; Vol. 15: No. 10, p.19

SLE (EULAR 2009) 45 Merrill EULAR 2009, Benlysta, BLISS 52 and 76

Lupus Nephritis 44 - 47 G. Apple JAm Soc Nephrol 2009, Cellcept vs. Cyclophosphamide

Multiple Sclerosis 50Communication of DMSG on

Fingolimod

http://www.dmsg.de/multiple-sklerose-

news/index.php?w3pid=news&kategorie=therapien&anr=

2310

Crohn's Disease - Primary non

responders to anti TNF-alpha30 - 40 Remo Panaccione, MD, FRCPC

Advanced Therapy of Inflammatory Bowel Disease,

Volume 2: IBD and Crohn's ... von Theodore

Bayless,Stephen B Hanauer

Crohn's Disease - Secondary

non responders to anti TNF-

alpha

30 - 40 Remo Panaccione, MD, FRCPC http://www.medscape.org/viewarticle/578444_3

Ulcerative Colitis 41 - 50 Walter Reinisch et. al. Gut 2011;60:780e787, Results of NCT00385736

Epilepsy (Lacosamide) 59 - 67 E Ben-Menachem Epilepsia 2007; 48 (7): 1308-17

Epilepsy (Zonisamide) 50 MJ Brodie Epilepsia 2005; 46(1):31-41

Parkinson's Disease

(Rotigotine)52 RL Watts et al. Neurology. 2007;68(4):272

Prevalence of non-Responders in AID Therapy

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Response Prediction- The Million Dollar Question

Case Study: Adalimumab & MTX in early RA

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MTX monotherapy Early RA

<1 year

T0 T48 T24

Adalimumab + MTX

Placebo + MTX

3a

3b

3c

1

Diagnosis Predicting

Remission

CONFIDENTIAL

2

Monitoring

Treatment

What have we done?

Protagen looked into a better diagnosis of patients (1), monitored treatment effects

(2) and investigated the possibility to predict remission (3)

Remission prediction and Non-Remission prediction marker were found by the

retrospective analysis of T0 (before first dosing) sera from early RA patients

Clinical endpoint results (DAS28) from T24 were available at time of analysis

Distinct markers predicting remission but also predicting non-remission for Humira

(3a), MTX (3c) and Humira/MTX (3b) were found

SeroTag® provides access to treatment specific response prediction

markers!

1

2 3

3a 3b 3c

CONFIDENTIAL - 16 -

Reactivity in

ADA/MTX Non-

Remission Group

Reactivity in

ADA/MTX

Remission Group

Distinct sets of autoantigens were identified for patients achieving/not achieving

remission at T24 by analyzing T0 samples!

Predicting Remission for Adalimumab and MTX A

ntigens

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PROTAGEN Introduction & SeroTag® Autoantibody Profiling

PROTAGEN Experience, Expertise & Product Portfolio

Case Study : Response Prediction in early RA

Investment Case

1

2

3

4

Agenda

Business Model

- 18 - CONFIDENTIAL

hPEX® & SeroTag®

Technology

SLE

IVD

RA AID

Value

Generation

IP Data

$

New Indications CDx

2017 +

SLE AID

Pharma

Collaborations

MS RA

IP Data

New Indications

CONFIDENTIAL -19-

Product Development Pipeline

Candidate Product

Indentifier Discovery Validation

Assay

Development

Prototype

Assay

Market

Launch

RA Dx CCPbetter & CCP-

Q4/2013 Q3/2014 Q1/2015

RA MTXpred CDx Q1/2014 Q4/2014 Q2/2015

RA TNFpred CDx Q2/2014 Q1/2015 Q3/2015

SLE Dx & CDx Q2/2014 Q3/2014 Q2/2015 Q4/2015

SSC Dx IVD & Prognosis

Q4/2013 Q2/2014 Q4/2014

AS Dx Q1/2014 Q2/2014 Q4/2014 Q2/2015

NMO Dx Q2/2014 Q1/2015 Q3/2015

Novel IVD Products for unmet diagnostic needs

Pharma Collaboration Market Potential

More than 2.000 Projects running today, attractive market

potential for Protagen

Active clinical trials which can profit from SeroTag®

Rheumatoid Arthritis

Lupus

IBD Multiple

Sclerosis

Thyroid Disease and

Endometriosis

Cancer Vaccines

~450

~470

~320

~350

~160

~270

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Executive Summary

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PROTAGEN AG

Privately owned, located in Dortmund, Germany

31 employees, VC-backed

Unique platform for novel IVD Products

Access to proprietary biomarkers for Dx and CDx

Blood serum-based technology – small samples, stable analytes

Strong pipeline in Autoimmune Diseases

Development of own IVD Test – market access 2015

Pharma Collaborations to generate revenue stream

Strategic Partnership with PAREXEL (CRO)

SeroTag® supports Drug Development in all Clinical Development Phases

Retention of Diagnostic Commercialization Rights, strong IP position

Unique position in stratified therapies and personalized medicine

CONFIDENTIAL

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Protagen AG

Otto-Hahn-Str. 15

44227 Dortmund

Germany

T + 49 231 9742 6300

F + 49 231 9742 6301

bd@protagen.com

www.protagen.com

CONFIDENTIAL