Advancing Antibody Therapeutics Bioteknologi i sentrum september

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1 AFFITECH Advancing Antibody Therapeutics Bioteknologi i sentrum september

2 Affitech AS is a leading human antibody discovery & development company with a focus on oncology, having two unique approaches for the discovery of fully human antibodies and several early-stage product candidates in its development pipeline. Affitech AS is located in Oslo, Norway and its US subsidiary, Affitech USA, Inc., is in the San Francisco Bay Area.

3 Affitech Executive Summary Establishment: Private company established in 1997 with HQ and R&D in Oslo, Norway Subsidiary: Affitech USA, Inc., a wholly owned subsidiary in operation in the San Francisco Bay Area since 2001 Employees: 35 plus Product Focus: Human Antibody Therapeutics Disease Focus: Oncology Products : Several candidates in preclinical research and development for various cancer entities Technologies: CBAS, AffiScreeN, Breitling IP family, Protein L Partnerships: Several corporate (Peregrine Inc., Viventia Biotech, NatImmune, Xoma, Roche) and academic partnerships Licencing Partners: Dyax, Xoma, unrevealed UK-based biotech company, LEN, DKFZ, DNR, Micromet, Pharmexa Marketed Products: Protein L and associated products for antibody and fragment separation Revenue source: Corporate partnerships and Protein L sales Shareholders: Norwegian blue chip investors with long-term commitment 2

4 Affitech Strategy Proprietary technologies and therapeutic product candidates Intellectual Property Rights Customer-initiated projects and product candidates Protein L franchise Develop a pipeline of fully human antibody therapeutic candidates Monetize proprietary technologies and product development and commercialization through collaborations and partnerships Aggressively protect, procure and pursue IP rights and licensing Establish a strong financial platform out of Protein L

5 Highly competent management and strong Board of Directors Affitech USA President Dr. Rathin Das Consultants Business Development, Non-clinical Product Development, Manufacturing, QA/QC SVP, Corp Develop & CBO Dr. Rathin Das Director, Strategic Alliances & Licensing Dr. Michael Braunagel Affitech AS CEO Dr. Martin Welschof Director Research & Development Dr. Björn Cochlovius 3 Group Leaders QA/QC Manager 3 Senior Scientists 11 Scientists 5 Engineers 8 Lab Ass/Interns Director Finance and Administration Hans Petter Tjeldflaat Board members Scientific advisory board Chairman; Øyvin Brøymer Independent investor Prof. Peter Hudson Scientific Director, CRC, Dr. Steinar J. Engelsen Partner, Teknoinvest Australia Pål M. Rødseth Investment Manager, Ferd Venture Prof. Inger Sandlie Professor, Department of Biology, UIO Arne Handeland Partner, Verdane Capital Prof. Rolf Seljelid Chairman Advanced Research Geir Stormorken Managing Director, Braganza Program, Research Council of Norway Dr. Ole Jørgen Marvik Managing Director, 4bio AS Prof. Lorenz Trümper Chairman Department of Dr. Thomas von Rüden CEO, Direvo AG Hematology and Oncology, Georg August University, Germany Prof. Arthur Mercurio Vice Chairman Massachusetts University School of Medicine, USA

6 Affitech s Collaborations Radium Hospital Radium Hospital NIPH Radium Hospital NUST Radium Hospital Heidelberg University Target Discovery Antibody Discovery Antibody Validation Production and Purification Preclinical Development XOMA Roche Peregrine NatImmune XOMA Roche Peregrine NatImmune XOMA SINTEF UK based biotech company CROs Peregrine Viventia Viventia Academic Partners Commercial Partners Licensing Partners: Dyax, XOMA, UK biotech company, LEN, DKFZ, DNR, Micromet, Pharmexa

7 Affitech Technologies Affitech utilizes two discrete but unique approaches for the discovery of fully human antibodies: Molecule Based Antibody Discovery (MBAS) : involves proprietary Phagemid ScreeN and AffiScreeN technologies and uses validated targets for discovery purpose. Cell Based Antibody Discovery (CBAS TM ): a unique disease-specific cell-based reverse-screening approach for discovering antibodies and subsequent identification of their cognate targets.

8 Molecule Based Antibody Discovery Methods 1. PhagemidScreening Phage display No phage display NAIVE LIBRARY SELECTION AND SCREENING 2. AffiScreeN TM scfv Lead candidates 1. Selection 2. Screening: 3. Engineering No phage display scfv or IgG Products PATIENT LIBRARY SCREENING Screening scfv Lead candidates/ Products Engineering (optional) scfv or IgG Products

9 Summary of Affitech s MBAS Antibody Discovery System Proprietary system. Holder of Breitling IP. Robust scfv library: >10e10 clones; All VH families present; IgM, IgD, IgG libraries; 30-50% functional clones. 2 step discovery and engineering processes generate scfvs with nanomolar to picomolar affinity. Fab and Full-length conversions of scfvs are done routinely. Full-length IgG of Affitech-discovered MAbs show excellent in vivo functionality AffiscreeN TM : Affitech s proprietary system. No selection step (e.g. phage display) required High throughput: From donor sample to high affinity antibodies within 4 weeks Targets utilized: Protein antigens, bacterial surface targets,viral targets,membrane vesicles and fragments Disease applications: Infectious disease, Cancer, Inflammation.

10 Technology-based partnership of Affitech Target-driven Collaborative discovery projects with partners Targets provided by partners Post discovery or Pre-clinical or Post-pre-clinical stage antibody products for licensing Partner-led revenuegenerating development agreements Affitech achieves various forms of financial upside (undisclosed) Project value Antibody Discovery Phases in drug development Affitech competence and capabilities Preclinical Clinical I Clinical II Clinical III Approved Partner competence and capabilities Year 1 Year 3 Year 5 Year X

11 Cell based antibody selection (CBAS ) METHOD (Part A) 1. Negative selection PHAGE level panning on negative cell type(s) reduction/elimination of unrelevant binders 2. Positive selection PHAGE level panning on cells of interest enrichment of specific binders 3. Final selection scfv level high troughput screening on cells selection of expressed and binding scfv

12 Cell Based Antibody Selection (CBAS TM ): METHOD (Part B) Identified scfvs 1 Full-length IgG STEPS: 1: Conversion to Full-length IgG 2: In vitro functionality tests 3. Tissue specificity tests 4. Identification of lead antibody 5. In vivo functionality tests 6. Selection of candidate for Pre-clinical Development 7. Target identification 8. Preclinical Development In vitro efficacy Tissue specificity by IHC Target identification Preclinical Development Identification of lead IgG In vivo efficacy Selected IgG Candidate

13 Cell based antibody selection (CBAS ) A unique method for explotation of various cell types for Antibody and Target discovery Cell type with (unknown) surface antigens e.g. cancer cell Cell transfected to express complicated target molecule Infected somatic cell with infection-specific surface antigens

14 CBAS Shortens Antibody Discovery Timeline Conventional Target-dependent Antibody Discovery Preclinical Development Antibody Validation Antibody Identification Target Validation Target Clinical Development Identification 4 5 years CBAS Antibody Preclinical Development Clinical Development Antibody Validation Selected Cells Identification Target Identification Target Validation 2 3 years

15 Advantages of Affitech s Proprietary CBAS System Generates both antibody and cognate targets. Utilizes intact and functionally/clinically validated cells. Generates antibodies against cell surface-bound target proteins in their natural conformation. Recognizes targets in their functional state with all post translational modifications. Applicable to the discovery of antibodies against transfected cells expressing a validated target(s). Facilitates discovery of antibodies with highest degree of specificity to diseased cells A complete in vitro system, does not require immunization or hybridoma technology. Applicable to the discovery of both internalizable and non-internalizable antibodies High potential for the discovery of cancer stem cell markers and MAbs against multiple membrane domain proteins such as GPCRs A significantly faster method than genomics/proteomics-based systems: High throughput comprehensive antibody/target discovery process cut cost and time requirements for drug discovery.

16 CBAS TM derived internal product candidates Results at hand: 1. Method of antibody isolation (scfv format) 2. Identification of antibody product candidates 3. Characterization of cellular binding and associated properties 4. Antibody engineering and conversion to full-length IgG 5. Cellular and Tissue specificity: rodent and human 6. In vitro and in vivo functionality 7. Target information 8. Generation of high-level IgG producing stable CHO cell line generation 9. Ongoing GLP/GMP production status 10. Ongoing De-fucosylated IgG production status.

17 Example: CBAS TM IgG Immunohistochemistry on tumors human glioblastoma crysosection human breast cancer crysosection human colon cancer crysosection human pancreatic cancer crysosection human kidney cancer crysosection human lung cancer crysosection human melanoma crysosection human prostate cancer crysosection Large study ongoing, including normal human tissues, mouse, monkey.

18 Product Development in Progress CBAS 141 (P) Breast Cancer Antibody Discovery Antibody Validation Preclinical Research Preclinical Development Clinical Development CBAS 173 Breast/Prostate Cancer Proprietary CBAS 132 Lung/Colorectal Cancer T-1 (P) Anti-angiogenesis Joint Development T-2 (P) Anti-angiogenesis T-3 (P) Virology Commercial Partner T-4 (P) Colorectal Cancer CBAS 220 Breast Cancer CBAS 207 Breast Cancer CBAS 7-12 Pancreatic Cancer CBAS Lung Cancer

19 Products Three CBAS-derived antibodies for various cancers. Antibodies are currently at various stages of pre-clinical research and development. Three antibodies discovered by the phagemid/high throughput screening system in association with our partners that are at various level of pre-clinical research and development. Several discovery-stage product candidates. High-yield bacterial production vectors which yields higher than 1 gram/liter recombinant antibody fragments and >5 gm/liter of Protein L. Affitech is the sole proprietor of Protein L, which is sold for detection and affinity purification of antibodies and antibody fragments.

20 AFFITECH Opportunities Strong Intellectual Property, FTO position, Cost-effective Business Model and Low Royalty Stacking A powerful phagemid library, AffiscreeN TM and AffiSelect TM Screening Systems the Breitling IP for antibody discovery (worldwide & Sublicenseable) Diabody and scfv IP (worldwide & Sublicenseable) FTO Product export capabilities Low royalty stacking Protein L & High producing bacterial production technology (Divesture or Exclusive License) State-of-the-art Antibody Discovery systems for Collaborations MBAS and AffiScreeN TM-- An efficient system for discovery of antibodies against defined molecular targets Success in several partnered projects In vivo validation of antibodies achieved CBAS-- A rigorous system for discovery of antibodies with selectivity for targets (either transgenic or unknown) in intact cells Success in partnered and unpartnered programs Several cancer antibodies with proven functionality discovered by Affitech currently in development and available for out-licensing.

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