The AutoImmuneDx Company
European Business Development Conference Düsseldorf , September 2013
Protagen AG
Otto-Hahn-Str. 15
D-44227 Dortmund
www.protagen.com
CONFIDENTIAL
Agenda
PROTAGEN Introduction & SeroTag® Autoantibody Profiling
1
2
PROTAGEN Experience, Expertise & Product Portfolio
3
Case Study : Response Prediction in early RA
4
CONFIDENTIAL
Investment Case
-2-
Protagen AG – Key Facts
Set-up:
 Experienced management team
 ISO 9001/2008 certified
Protagen HQ, Germany
Expertise
 Unique, exploratory SeroTag® approach
for Dx/CDx development
 Focus on autoimmune diseases
 Excellent IP position
1000 m² lab facilities
Financial status
 Privately held
 Committed, long-standing investors
Human Protein Library
CONFIDENTIAL
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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!
Biggest
Expression
Library
High
Throughput
Measurement
Leading
Analysis
Team
Impeccable
Quality
 Applicable to Dx & CDx
development
CONFIDENTIAL
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SeroTag® - The Technology
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® technology employs autoantibodies as biomarkers
CONFIDENTIAL
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Business Model
hPEX® & SeroTag®
Technology
RA
Data
New
Indications
Pharma
Collaborations
IVD
AID
SLE
RA
SLE
AID
MS
$
IP Data
IP
New
Indications
CDx
2017 +
Value
Generation
CONFIDENTIAL
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Agenda
PROTAGEN Introduction & SeroTag® Autoantibody Profiling
1
2
PROTAGEN Experience, Expertise & Product Portfolio
3
Case Study : Response Prediction in early RA
4
CONFIDENTIAL
Investment Case
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Drug Development for Autoimmune Therapy
An endeavour with many challenges
Average non-responder rate in Autoimmune Disease Drug Therapy ~ 50%
PROTAGEN
Increases your chances!
Sales of 9.3 billion US$ in 2012
CONFIDENTIAL
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Experience & Expertise
Core Area: Rheumatology & Immunology
Why Immunology/
Autoimmune-Diseases?
RA;
Early RA 75 SLE;
130
Humira/
MTX
Study;
Healthy;
349
250
AS; 82
PSS; 100
Early
Arthritis;
751
 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
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RA in vitro Diagnostic Assays – Current Status
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%
?
yes
no
yes
Correlation to outcome
yes
yes
yes
Yes
Association to extra-cellular
manifestation
yes
yes
yes
unkonwn
Disease activity correlation
RF: rheumatoid factor
• Established IVD market in RA
• With room for improvement of sensitivity
• And a clear need for additional IVDs, in particular for seronegative
patients
CONFIDENTIAL
Egerer et al; 2009 (Dtsch. Ärzteblatt) - 10 -
PROTAGEN Market Overview
Market
Importance
≈
≈
Market Size
- 11 -
Agenda
PROTAGEN Introduction & SeroTag® Autoantibody Profiling
1
2
PROTAGEN Experience, Expertise & Product Portfolio
3
Case Study : Response Prediction in early RA
4
CONFIDENTIAL
Investment Case
- 12 -
Prevalence of non-Responders in AID Therapy
Disease
Average % of
nonResponders
Author
Citation
Rheumatoid Arthritis (ACR20)
28 - 58
Craig Beavers et al.
Orthopedics
January 2010 - Volume 33 · Issue 1
40
C McLeod et al.
Health Technol Assess 2007;11:1–158
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
50
Communication of DMSG on
Fingolimod
http://www.dmsg.de/multiple-sklerosenews/index.php?w3pid=news&kategorie=therapien&anr=
2310
Ankylosing spondylitis (ASAS
20)
Psoriatic Arthritis (MEASE
2004, 24weeks, PsARC and
ARC50)
Multiple Sclerosis
Crohn's Disease - Primary non
responders to anti TNF-alpha
30 - 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 TNFalpha
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)
Epilepsy (Zonisamide)
Parkinson's Disease
(Rotigotine)
59 - 67
50
E Ben-Menachem
MJ Brodie
Epilepsia 2007; 48 (7): 1308-17
Epilepsia 2005; 46(1):31-41
52
RL Watts et al.
Neurology. 2007;68(4):272
CONFIDENTIAL
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Response Prediction- The Million Dollar Question
CONFIDENTIAL
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Case Study: Adalimumab & MTX in early RA
Adalimumab + MTX
3a
Early RA
1
Diagnosis
2
3b
<1 year
T0
MTX monotherapy
3c
Placebo + MTX
T24
T48
Predicting
Remission
Monitoring
Treatment
What have we done?
1 monitored treatment effects
 Protagen looked into a better diagnosis of patients (1),
(2)
3
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
3b
(3a),
and Humira/MTX (3b)
were found
3a MTX (3c)
3c
SeroTag® provides access to treatment specific response prediction
markers!
CONFIDENTIAL
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Predicting Remission for Adalimumab and MTX
Antigens
Reactivity in
ADA/MTX NonRemission 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!
CONFIDENTIAL
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Agenda
PROTAGEN Introduction & SeroTag® Autoantibody Profiling
1
2
PROTAGEN Experience, Expertise & Product Portfolio
3
Case Study : Response Prediction in early RA
4
CONFIDENTIAL
Investment Case
- 17 -
Business Model
hPEX® & SeroTag®
Technology
RA
Data
New
Indications
Pharma
Collaborations
IVD
AID
SLE
RA
SLE
AID
MS
$
IP Data
IP
New
Indications
CDx
2017 +
Value
Generation
CONFIDENTIAL
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Product Development Pipeline
Candidate
Product
Indentifier
Assay
Development
Prototype
Assay
Market
Launch
RA
Dx
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
Q3/2014
Q2/2015
Q4/2015
SSC
Dx
Q4/2013
Q2/2014
Q4/2014
AS
Dx
Q2/2014
Q4/2014
Q2/2015
NMO
Dx
Q2/2014
Q1/2015
Q3/2015
Discovery
Validation
CCPbetter & CCP-
Q2/2014
IVD & Prognosis
Q1/2014
Novel IVD Products for unmet diagnostic needs
CONFIDENTIAL
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Pharma Collaboration Market Potential
Active clinical trials which can profit from SeroTag®
Cancer
Vaccines
Rheumatoid
Arthritis
~350
Thyroid
Disease and
Endometriosis
~450
~320
~270
Multiple
Sclerosis
~160
Lupus
~470
IBD
More than 2.000 Projects running today, attractive market
potential for Protagen
CONFIDENTIAL
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Executive Summary
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
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