NEW LEADS FOR RESEARCH, DIAGNOSTIC & THERAPEUTIC APPLICATIONS
Dr. J.M.H. RaatsØ 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 NijmegenØ 2002 Biopartner First Stage grant.Ø 2004 Managing Director ModiQuest B.V.Ø 2005 Managing Director ModiQuest Research B.V.
Companies Universities & Clinics NCMLS Nijmegen Center for Molecular Life Sciences 3
The StartInvention of Diagnostic kit for early detection of RA
Business planContents 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
FinancesVenture 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
Intellectual PropertyPatents• 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!
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
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
First Business ConceptØ 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.
Antibody generation Research Diagnostics Immunisation PatientsTherapeutics Imaging Polyclonal Production monoclonal serum, eggs antibodies in tissue culture Hybridoma B-cells Recombinant antibody
Resources requiredØ Acquire IP rights on technologiesØ 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 ChiralixUMCN FNWI Euro DiagnosticaDr. William Leenders Prof. Jan van Hest Future DiagnosticsDr. Rob Woestenenk Prof. Floris RutjesProf. Wim van de Berg Prof. Ger Pruijn SpinnovationDr. Leo JoostenDr. Peter van Lent Techno-Centrum Synthon Dr. Stef OlsthoornProf. Robert SauerweinDr. Will Roeffen CDL Pepscan HAN LUMC Dr. Jan Wouter Drijfhout CONICET: Argentinië Dr. Mariano Levin
Netherlands Classical ArgentinaProprietary 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 • MouseFully Human or Animal derived antibodies • Rabbit • LlamaReclone antibodies in different format Large proprietary vector set Library generation serviceHumanize, mousenize, chickenize, chimera for recombinant antibody production -Human IgG1, IgG3, IgG4, IgA, IgM -Mouse IgG1, IgG2a, IgG2b, IgG3 -Chicken IgY High throughput (bio)assay developmentClonePix 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 linesHigh throughput for robotic screeningcell line generation
NijmegenNCMLS Oss2004Trigon2006 LSP-Oss 2012 Molenweg 50, 5349 AC Oss, The Netherlands.Huygens2008
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 modelBusiness model• Contract Research Organization (MQR)• Development of novel diagnostics & proprietary drug candidates (MQT)Founded• 2004• 2005 founding of sister company MQRLocation• Oss, The Netherlands à 16 employees• Buenos Aires, Argentina à 2 employee
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
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
Patent position: • B-cell selection and culture • Protein modification specific antibodies (citrulline modification) • Novel therapeutics for rheumatoid arthritis • Novel tumor target
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
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
Preclinical proof of concept data PoC anti-CCP Abs in CAIA modelRhmAb2.102 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
Novel unique approachü 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 RAü 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
Partnering strategyModiQuest 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 peptidecompound 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.
ModiQuest WorkflowPre-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