Overview of Our Integrated Proteomics and Bioinformatics Services Platform The Systems Proteomics Company 2011 March 25 The Kinexus Discovery Platform IN VIVO SERVICES KINEX MICROARRAY SERVICES IMMUNOHISTOCHEM GRAPHICS SERVICES KINETWORKS BLOTTING SERVICES MASS SPEC SERVICES IN SILICO SERVICES PROBE PRODUCTION SERVICES We have created a highly integrated platform of unique proteomics and bioinformatics services to identify disease biomarkers and drug targets and to foster signal transduction research Our proteomics services are unmatched by any company for convenience, breadth, accuracy, cost and turn-around time 2 Services IN VIVO SERVICES CELL CULTURE KINEX MICROARRAY SERVICES KINETWORKS BLOTTING SERVICES 12 16 cell cell lines lines MASS SPEC SERVICES IN SILICO SERVICES PROBE PRODUCTION SERVICES Kinexus offers cell lysates from 16 of the most commonly studied human tumour cell lines prepared according to client specifications for proteomics analysis 3 Services IN VIVO SERVICES CELL CULTURE ANIMAL TISSUES KINEX MICROARRAY SERVICES KINETWORKS BLOTTING SERVICES 12 16 cell cell lines lines >40 monkey, rat + mouse tissues MASS SPEC SERVICES ANTIBODY VALIDATION PROTEIN CHARACTERIZATION IN SILICO SERVICES PROBE PRODUCTION SERVICES Clients can also choose from over 230 pre-made cell and tissue lysates for use in our proteomics services 4 Microarray Services IN VIVO SERVICES KINEX MICROARRAY SERVICES ANTIBODY MICROARRAYS KINETWORKS BLOTTING SERVICES MASS SPEC SERVICES IN SILICO SERVICES PROBE PRODUCTION SERVICES >800 >650 antibodies Close up of 1 of 16 grids on a Kinex™ Antibody Microarray - control (blue) and treated (red) have been overlaid and staggered for comparison. 5 Microarray Services IN VIVO SERVICES KINEX MICROARRAY SERVICES KINETWORKS BLOTTING SERVICES MASS SPEC SERVICES ANTIBODY MICROARRAYS >800 >650 antibodies REVERSE MICROARRAYS >230 lysates IN SILICO SERVICES PROBE PRODUCTION SERVICES Close up of a section of the Standard Kinex™ Reverse Lysate Microarray. Custom KRLM chips can also be produced for our clients with their own cell/tissue lysates. 6 Microarray Services IN VIVO SERVICES KINEX MICROARRAY SERVICES KINETWORKS BLOTTING SERVICES MASS SPEC SERVICES ANTIBODY MICROARRAYS >800 >650 antibodies REVERSE MICROARRAYS >230 lysates PROTEIN KINASE MICROARRAYS ~200 kinases IN SILICO SERVICES PROBE PRODUCTION SERVICES Close up of a section of the Kinex™ Protein Kinase Microarray. The binding of an ATP analogue to active protein kinase is shown. 7 Microarray Services IN VIVO SERVICES KINEX MICROARRAY SERVICES KINETWORKS BLOTTING SERVICES MASS SPEC SERVICES ANTIBODY MICROARRAYS >800 antibodies >650 REVERSE MICROARRAYS >230 lysates PROTEIN KINASE MICROARRAYS ~200 kinases PEPTIDE MICROARRAYS IN SILICO SERVICES PROBE PRODUCTION SERVICES Close up of a section of the Kinex™ Kinase Substrate Microarray chip. The binding of a phosphate detection dye to phosphorylated peptides is shown. ~450 peptides 8 Multi-Immunoblotting Services IN VIVO SERVICES KINEX MICROARRAY SERVICES Kinases Phosphatases KINETWORKS BLOTTING SERVICES PAN-SPECIFIC AB MASS SPEC SERVICES IN SILICO SERVICES PROBE PRODUCTION SERVICES 2 screens KPKS-1.2 multi-immunoblot showing half of the protein kinases detected with this screen. 9 Multi-Immunoblotting Services IN VIVO SERVICES KINEX MICROARRAY SERVICES KINETWORKS BLOTTING SERVICES MASS SPEC SERVICES IN SILICO SERVICES Kinases Phosphatases PAN-SPECIFIC AB 2 screens Phosphosites PHOSPHOSPECIFIC AB 4 screens PROBE PRODUCTION SERVICES Overlay of two KPSS multi-immunoblots showing the effects of staurosporin on Jurkat T cell phosphorylation. Red bands correspond to increased phosphorylation and blue bands reveal decreases in phosphorylation. 10 Multi-Immunoblotting Services IN VIVO SERVICES KINEX MICROARRAY SERVICES KINETWORKS BLOTTING SERVICES MASS SPEC SERVICES IN SILICO SERVICES Kinases Phosphatases PAN-SPECIFIC AB 2 screens Phosphosites PHOSPHOSPECIFIC AB 4 screens CUSTOM AB 2 screens PROBE PRODUCTION SERVICES KCPS 1.0 - 18 antibodies tested on 1 lysate sample KCSS 1.0 - 8 cell/tissue samples tested with up to 3 antibodies 11 Mass Spectrometry Services IN VIVO SERVICES KINEX MICROARRAY SERVICES KINETWORKS BLOTTING SERVICES Identify crossreactive proteins MASS SPEC SERVICES PROBE PRODUCTION SERVICES PROTEIN ID PROTEOME PHOSPHORYLATION Identify phosphosites in a protein IN SILICO SERVICES Track hundreds of phosphosites PROTEIN PHOSPHORYLATION KINASE SUBSTRATE PROFILING Identify kinase Substrate proteins 12 In Silico Prediction Services IN VIVO SERVICES KINEX MICROARRAY SERVICES KINETWORKS BLOTTING SERVICES MASS SPEC SERVICES Obtain a specificity matrix for a kinase Identify kinases for a phosphosite IN SILICO SERVICES PROBE PRODUCTION SERVICES KINASE SPECIFICITY PREDICTION KINASE MATCH PREDICTION Identify substrates of a kinase PHOSPHOPROTEIN MATCH PREDICTION Identify kinases for many phosphosites 13 Probe Production Services IN VIVO SERVICES KINEX MICROARRAY SERVICES KINETWORKS BLOTTING SERVICES MASS SPEC SERVICES Active enzymes and substrates IN SILICO SERVICES PROBE PRODUCTION SERVICES RECOMBINANT PROTEINS SYNTHETIC PEPTIDES Soluble peptides Peptides on macroarrays PEPTIDE ARRAYS Peptides on microarrays 14 Antibody-driven Biomarker Discovery PREPARATION In Vivo custom cell culture and treatment DISCOVERY Kinex™ Antibody Microarrays VALIDATION Kinetworks™ Multi-immunoblotting VALIDATION Kinex™ Reverse Lysate Microarrays LOCATION IHC Immunohistochemistry CORRELATION KiNET and SigNET websites 15 Protein Kinase Drugs More than 30% of world EGF receptor 3D structure with kinase inhibitor drug Tarceva pharmaceutical research is focused on protein kinases Over 400 human diseases linked to defects in kinase signalling 19 drugs approved and > 150 in clinical trials Most kinase inhibitors in clinical development are for cancer treatment 16 Kinexus Discovery Platform Assists All Phases of Drug Discovery and Development DRUG TARGET DISCOVERY DRUG TARGET VALIDATION PROTEIN SCREENING IN VIVO CELL/TISSUE SCREENING MICROARRAYS MULTI-BLOT DRUG DISCOVERY DRUG ANALYSIS HTP COMPOUND SCREENING MASS SPEC CELLS MECHANISM IN SILICO ANIMALS TOXICOLOGY HUMAN PHASE I, II + III TRIALS PATIENT SCREENING PRE-CLINICAL VALIDATION CLINICAL VALIDATION BIOMARKER DISCOVERY PROBE PRODUCTION 17 Kinexus Services for Kinase Drug Discovery DRUG TARGET KINASE DISCOVERY PROTEIN SCREENING KINASE SUBSTRATE DISCOVERY KINASE ASSAY DEVELOPMENT CELL/TISSUE SCREENING HTP COMPOUND SCREENING KINASE DRUG SPECIFICITY Kinex™ KAM In Silico - IKSP Kinetworks™ Kinex™ - KKSM In Silico Prediction Peptide Production KiNET DB Kinase Testing - IKPT SigNET KB CELLS MECHANISM In Silico - IKMP Kinex™ KAM - CKSP Mass Spec - MSKS Binding Assays - Kinex™ - KPKM Kinex™ KPKM Activity Assays - KICP 18 KiNET DataBase Online at www.kinet.ca KiNET DATABANK Kinetworks™ Immunoblotting DataBase First launched in 2006 Features results from >6,000 immunoblots Over 200,000 protein measurements Search by protein, treatment or cell/tissue Over 95% unpublished data 19 SigNET KnowledgeBank Online at www.phosphonet.ca SigNET KNOWLEDGEBANK PhosphoNET KnowledgeBase Free, online access >92,000 confirmed and 560,000 predicted human phosphorylation sites >23,000 human proteins Functional information for ~2% of phosphosites Evolutionary analyses Kinase prediction 20 www.kinexus.ca ADVISORY BOARD Kinexus Bioinformatics Corp. Suite 1, 8755 Ash Street Vancouver, B.C. Canada V6P 6T3 Phone: 1-604-323-2547 Facsimile: 1-604-323-2548 E-mail: info@kinexus.ca 21