NEW LEADS FOR RESEARCH,  DIAGNOSTIC & THERAPEUTIC APPLICATIONS

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.

Dr. J.M.H. Raats Ø  1991 - 1994: Research Fellow; “Wellcome/CRC

Institute” Cambridge UK.

3

NCMLS Nijmegen Center for

Molecular Life Sciences

Companies Universities & Clinics

The Start

Invention of Diagnostic kit for early detection of RA

Business plan

Contents •  Company description •  Product/ service description •  Business economics •  Marketing plan •  Design & Development plan •  Manufacturing & Operations plan •  Management team •  Schedule •  Critical risks, problems, assumptions •  Financial plan •  Appendices

Reason •  Planning

•  Who are customers? •  Why/ what do customers buy? •  What will customers pay? •  What resources are needed?

•  Need for financing •  Strategic partnering

•  Jargon: •  Elevator pitch •  Executive summary •  Business plan

Finances

Venture capital •  How much money?

•  Valuation •  Timing •  What type of capital?

•  Angel investors •  Large VC companies

•  Added value: partners! •  VC network/ contacts

•  Risks •  Exit strategy (IPO/ Sale) •  Others own company

Growing from within •  Limited amount of ‘seed capital’ •  Investment of generated ‘profit’ Government funding •  Economic development grants

•  IOP •  CTMM •  SenterNovem •  FW7

•  Regional development initiatives •  Pieken in de Delta •  Euregio •  Health Valley

Intellectual Property

Patents •  Promote progress of useful arts • ‘Quid pro Quo’ •  Invention:

•  Novel •  No prior public disclosure

•  Useful •  Non-obvious

•  Alternative: trade secrets!

•  Validity: 20 years •  Publication: 18 months after filing •  Enforcement/ infringement •  Licensing •  High Cost

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

•  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

Spin-out from University

 NEW TARGETS FOR (AUTOIMMUNE) DIAGNOSTICS

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.

Immunisation

Antibody generation

serum, eggs Polyclonal

B-cells Recombinant antibody

Patients

Production monoclonal antibodies

in tissue culture

Research

Therapeutics Imaging

Diagnostics

Hybridoma

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

Important collaborations

UMCN Dr. William Leenders Dr. Rob Woestenenk Prof. Wim van de Berg Dr. Leo Joosten Dr. Peter van Lent Prof. Robert Sauerwein Dr. Will Roeffen

FNWI Prof. Jan van Hest Prof. Floris Rutjes Prof. Ger Pruijn Techno-Centrum Dr. Stef Olsthoorn CDL HAN

Chiralix Euro Diagnostica Future Diagnostics Spinnovation Synthon

Pepscan

LUMC Dr. Jan Wouter Drijfhout

CONICET: Argentinië Dr. Mariano Levin

Antibody generation

Classical Proprietary technology

•  B-cell selection/culture •  Electrofusion •  High throughput ClonePix robot

for third party services Simultaneous screening on: antigen reactivity antibody isotype production level

Fully Human or Animal derived antibodies

human naïve and patient derived recombinant antibody libraries

• Autoimmune diseases • Malaria • Chagas

Animal derived libraries naïve & immune • Chicken • Mouse • Rabbit • Llama

Library generation service

Argentina Netherlands

Large proprietary vector set for recombinant antibody production -Human IgG1, IgG3, IgG4, IgA, IgM -Mouse IgG1, IgG2a, IgG2b, IgG3 -Chicken IgY

Reclone antibodies in different format Humanize, mousenize, chickenize, chimera

High throughput cell line generation

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 for robotic screening

ClonePix

High throughput (bio)assay development

Efficient cell transformation (Amaxa)

Nijmegen

NCMLS 2004

Trigon 2006

Huygens 2008

Oss

LSP-Oss 2012

Molenweg 50, 5349 AC Oss, The Netherlands.

 NEW ANTIBODY LEADS FOR RESEARCH,  DIAGNOSTIC & THERAPEUTIC APPLICATIONS

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

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

•  Proteomics screening technology

•  B-cell selection and culture

•  Very efficient proprietary electrofusion technology

•  Human & animal antibody libraries

•  High through-put stable cell line generation

Technology

•  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

CRO activities

Fully integrated Technology platform

(Bio) Assay development Quality Control

Proprietary mammalian expression vector set (pMQR)

Highly efficient Nucleofection (Amaxa)

High-throughput cell sorting (ClonePix FL)

Antibody production (mammalian cell culture)

Analysis/ characterization

FPLC-based antibody purification (AKTA)

Stable Antibody-expressing cell lines

Hybridoma Recombinant antibodies

•  B-cell selection and culture

•  Protein modification specific antibodies (citrulline modification)

•  Novel therapeutics for rheumatoid arthritis

•  Novel tumor target

Patent position:

In-house research focus: Auto-immune disorders

Rheumatoid Arthritis •  Systemic auto-immune disorder •  Chronic inflammation of joints •  Current Treatment:

•  Painkillers •  Anti-inflammatory drugs

Research @ ModiQuest •  Mouse RA models

•  Anti-inflammatory compounds

RA patient

4.  Diagnostic CCP RA test sold worldwide by licensees

Euro-Diagnostica and Axis-Shield.

2.  Citrullinated peptide has been developed which is recognised by the vast majority of RA sera.

1.  RA patients (and only RA patients) make antibodies against

modified arginine (citrulline).

Schellekens et al. J Clin Invest 1998, 101: 273-281 and Arthritis Rheum 2000, 43: 155-163

3. Detecting RA up to 10 years before onset disease.

The start: Proprietary Anti-CCP-test

Diagnostic kit for early detection of RA

PoC anti-CCP Abs in CAIA model

Preclinical proof of concept data

RhmAb2.102 prevents onset of inflammation

Anti-coll-II mix

LPS + Abs

•  Human anti-CCP antibodies are not pathogenic in mice

•  Some human anti-CCP antibodies limit or completely prevent the onset of the inflammatory response

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

Novel unique approach

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.

Partnering strategy

Antigen Selection

Antibody Generation

Antibody Optimization

Antibody Production

Assay Development

•  Peptide Design & Modeling •  Peptide synthesis •  # different immunization techniques

•  Proprietary fusion method •  # different strains available •  # different techniques on different species available

•  Polyclonal •  Hybridoma monoclonal •  B-cell selection, monoclonal •  Phage Display, recombinant monoclonal

•  Antibody sequencing •  Affinity maturation •  # different proprietary vectors available for reformatting and/or chimerization •  Humanization

•  Many cell lines available •  Transient production •  Stable cell line

•  Gene amplification •  Up to grams scale production

•  Functionality study •  Affinity (Biacore/Octet) •  Bio-Assay •  Animal model

ModiQuest Workflow Pre-clinical lead candidate development

Antibody Processing

•  Labeling •  Purification