27-09-2012 ModiQuest (Jos Raats)

1. NEW LEADS FOR RESEARCH,
DIAGNOSTIC & THERAPEUTIC APPLICATIONS

2. Dr. J.M.H. Raats
Ø 1991 - 1994: Research Fellow; “Wellcome/CRC
Institute” Cambridge UK.
Ø 1994: Research Fellow; University of Minnesota,
Minneapolis, USA.
Ø 1994 - 1997: Post-Doc; KU Nijmegen (Dep. Biochemistry).
Ø 1998 - 2002: Research Scientist; Future Diagnostics B.V.
(Wychen).
Ø 1998 - 2001: KNAW Research Fellow; KU Nijmegen (Dep.
Biochemistry).
Ø 2001 Assistant Professor KU Nijmegen
Ø 2002 Biopartner First Stage grant.
Ø 2004 Managing Director ModiQuest B.V.
Ø 2005 Managing Director ModiQuest Research B.V.

3. Companies Universities & Clinics
NCMLS
Nijmegen Center for
Molecular Life Sciences
3

4. The Start
Invention of Diagnostic kit for early detection of RA

5. Business plan
Contents Reason
• Company description • Planning
• Product/ service description • Who are customers?
• Business economics • Why/ what do customers buy?
• Marketing plan • What will customers pay?
• Design & Development plan • What resources are needed?
• Manufacturing & Operations plan • Need for financing
• Management team • Strategic partnering
• Schedule
• Critical risks, problems, assumptions • Jargon:
• Financial plan • Elevator pitch
• Appendices • Executive summary
• Business plan

6. Finances
Venture capital Growing from within
• How much money? • Limited amount of ‘seed capital’
• Valuation • Investment of generated ‘profit’
• Timing Government funding
• What type of capital? • Economic development grants
• Angel investors • IOP
• Large VC companies • CTMM
• Added value: partners! • SenterNovem
• VC network/ contacts • FW7
• Risks • Regional development initiatives
• Exit strategy (IPO/ Sale) • Pieken in de Delta
• Others own company • Euregio
• Health Valley

7. Intellectual Property
Patents
• Promote progress of useful arts
• ‘Quid pro Quo’
• Invention: • Validity: 20 years
• Novel • Publication: 18 months after filing
• No prior public disclosure • Enforcement/ infringement
• Useful • Licensing
• Non-obvious • High Cost
• Alternative: trade secrets!

8. Spin-out from University
• In 90’ not very common in Nijmegen
• Took very very long time to arrange and agree with University
on par time employment, and knowledge & IP transfer
– First discussions in 1997 …… actual start 2004
– No transfer bureaus at that time
• Difficult to arrange / rent labspace
Key persons involved in the actual start:
Dr. Piet Timmermans – Vice Decaan FNWI
Prof. Walther van Venrooij – Head department Biochemistry

9. Spin-out from University
• During start-up fase (1997-2002) gained business
experience in other company (Future Diagnostics)
• Par time in Academia
• Obtained Bio-Partner start up grant 2002-2004
– Allowed actual start-up financially
• Provided start-up financing for feasibility phase
• Allowed attending Bio-Partner Master Class
à Wrote first business plan
à Provided lots of knowledge regarding business
development
à Obtained excellent network of other start-up
entrepreneurs as well as experienced business
people

10. NEW TARGETS FOR (AUTOIMMUNE) DIAGNOSTICS

11. First Business Concept
Ø Use new target discovery methods to identify novel (post-
translationally modified) targets for (autoimmune) disorders.
Ø Develop or in-license new tools and technologies to improve
existing, or create new diagnostic techniques and
applications.
Ø These targets, tools and technologies (TTT) will be out-
licensed to diagnostic companies. Alternatively, diagnostic
tests based on these TTT will be developed in-house or with
partner companies.
Ø Marketing of TTT for contract research applications.

12. Antibody generation
Research Diagnostics
Immunisation
Patients
Therapeutics Imaging
Polyclonal
Production monoclonal serum, eggs
antibodies
in tissue culture
Hybridoma
B-cells
Recombinant
antibody

13. Resources required
Ø Acquire IP rights on technologies
Ø Financial resources for (Pilot) projects
• Provides access to new targets and technologies that can not be
developed on its own.
Ø Start building client base to obtain additional financial
resources
• Allows for matching grants
• Obtain grants to develop internal pipeline faster
Ø Setup collaborations
• to develop internal pipeline faster and gain access to new technologies

14. Important collaborations
Chiralix
UMCN FNWI
Euro Diagnostica
Dr. William Leenders Prof. Jan van Hest
Future Diagnostics
Dr. Rob Woestenenk Prof. Floris Rutjes
Prof. Wim van de Berg Prof. Ger Pruijn Spinnovation
Dr. Leo Joosten
Dr. Peter van Lent Techno-Centrum Synthon
Dr. Stef Olsthoorn
Prof. Robert Sauerwein
Dr. Will Roeffen CDL Pepscan
HAN LUMC
Dr. Jan Wouter Drijfhout
CONICET: Argentinië
Dr. Mariano Levin

15. Netherlands
Classical
Argentina
Proprietary technology human naïve and patient derived
• B-cell selection/culture
• Electrofusion
Antibody generation recombinant antibody libraries
• Autoimmune diseases
• High throughput ClonePix robot • Malaria
for third party services • Chagas
Simultaneous screening on:
antigen reactivity Animal derived libraries naïve & immune
antibody isotype • Chicken
production level • Mouse
Fully Human or Animal derived antibodies • Rabbit
• Llama
Reclone antibodies in different format Large proprietary vector set Library generation service
Humanize, mousenize, chickenize, chimera for recombinant antibody production
-Human IgG1, IgG3, IgG4, IgA, IgM
-Mouse IgG1, IgG2a, IgG2b, IgG3
-Chicken IgY
High throughput
(bio)assay development
ClonePix
Efficient cell transformation (Amaxa)
Identification and isolation of
highest producer cell lines
(antibodies or client products)
Stabilization of cell lines
Various cell lines available:
CHO
SP20
Adaptation of client cell lines
High throughput for robotic screening
cell line generation

16. Nijmegen
NCMLS
Oss
2004
Trigon
2006 LSP-Oss
2012
Molenweg 50, 5349 AC Oss,
The Netherlands.
Huygens
2008

17. NEW ANTIBODY LEADS FOR RESEARCH,
DIAGNOSTIC & THERAPEUTIC APPLICATIONS

18. The Team
CEO: Dr. Jos Raats
• Employees: Academic & Engineers
• Scientific advisory board:
Prof. Dr. W. van Venrooij & Prof Dr. G. Pruijn
• Strategic advisory board:
Dr. H. van Es
• Clinical advisory board:
Prof. Dr. Huizinga

19. Business model
Business model
• Contract Research Organization (MQR)
• Development of novel diagnostics & proprietary drug candidates
(MQT)
Founded
• 2004
• 2005 founding of sister company MQR
Location
• Oss, The Netherlands à 16 employees
• Buenos Aires, Argentina à 2 employee

20. Technology
• Proteomics screening technology
• B-cell selection and culture
• Very efficient proprietary electrofusion
technology
• Human & animal antibody libraries
• High through-put stable cell line
generation

21. CRO activities
• Hybridoma services
• B-cell selection and electrofusion
• B-cell selection and cloning
• Antibody sequencing & hybridoma cloning
• Phage display services
• Recombinant antibody services
• Transient antibody production
• Stable recombinant cell line generation

22. Fully integrated Technology platform
Recombinant Hybridoma
antibodies
Highly efficient
Nucleofection (Amaxa)
Proprietary mammalian
expression vector set (pMQR)
High-throughput cell sorting (ClonePix FL)
Stable Antibody-expressing cell lines
(Bio) Assay development
Quality Control
Analysis/ characterization
Antibody production (mammalian cell culture)
FPLC-based antibody purification (AKTA)

23. Patent position:
• B-cell selection and culture
• Protein modification specific antibodies
(citrulline modification)
• Novel therapeutics for rheumatoid
arthritis
• Novel tumor target

24. In-house research focus:
Auto-immune disorders
Rheumatoid Arthritis
• Systemic auto-immune disorder
RA patient
• Chronic inflammation of joints
• Current Treatment:
• Painkillers
• Anti-inflammatory drugs
Research @ ModiQuest
• Mouse RA models
• Anti-inflammatory compounds

25. The start:
Proprietary Anti-CCP-test
Diagnostic kit for early detection of RA
1. RA patients (and only RA patients) make antibodies against
modified arginine (citrulline).
2. Citrullinated peptide has been developed which is
recognised by the vast majority of RA sera.
3. Detecting RA up to 10 years before onset disease.
4. Diagnostic CCP RA test sold worldwide by licensees
Euro-Diagnostica and Axis-Shield.
Schellekens et al. J Clin Invest 1998, 101: 273-281 and Arthritis Rheum 2000, 43: 155-163

26. Preclinical proof of concept data
PoC anti-CCP Abs in CAIA model
RhmAb2.102 prevents onset of inflammation
• Human anti-CCP antibodies are
not pathogenic in mice
• Some human anti-CCP antibodies
limit or completely prevent the
onset of the inflammatory response
Anti-coll-II LPS +
mix Abs

27. Novel unique approach
ü Excellent diagnostic CCP test available for early detection of disease
- detecting RA up to 10 years before onset of disease
- allows identification of patients for early treatment of RA
ü Novel therapeutic approach for RA
- allows treatment at an early stage of disease without the usual
negative side effects of the currently available treatments
- preventing irreversible joint damage

28. Partnering strategy
ModiQuest is actively seeking R&D, Diagnostic, Biotech and Pharma companies:
ü To build strategic partnerships, utilizing its unique combination of excellent fee-for-service
antibody generation, engineering and optimization technologies.
ModiQuest has a proprietary fully human antibody and a proprietary peptide
compound in advanced preclinical development for Rheumatoid Arthritis.
ModiQuest is looking:
ü to out-license its current compounds under development.
ü for investors to facilitate the further development of its products.

29. ModiQuest Workflow
Pre-clinical lead candidate development
Antigen Antibody Antibody Antibody Antibody Assay
Selection Generation Optimization Production Processing Development
• Peptide Design & Modeling • Antibody sequencing • Labeling
• Peptide synthesis • Affinity maturation • Purification
• # different immunization • # different proprietary vectors
techniques available for reformatting
and/or chimerization
• Humanization
• Proprietary fusion method • Many cell lines available • Functionality study
• # different strains available • Transient production • Affinity (Biacore/Octet)
• # different techniques on different • Stable cell line • Bio-Assay
species available • Gene amplification • Animal model
• Polyclonal • Up to grams scale production
• Hybridoma monoclonal
• B-cell selection, monoclonal
• Phage Display, recombinant
monoclonal