From Genomics to Drugs Kitasato University – Harvard School of Public Health Symposium Kevin Rakin President & CEO

Genaissance Today Our Focus: Drug response Our Approach: Integrating gene variation into product development and drug marketing GNSC

Number of Patients Drug Response The Genaissance Drug Paradigm HAP Technology shifts the drug response curve Safer and more effective prescriptions Ability to move market share Conventional Drugs HAP Technology Guided Drugs

Leveraging our Platform DecoGen® Informatics System HAP Database HAP Typing Facility HAP Technology Internal Programs Partnerships Technology Drug- Specific Clinical Genetic Expertise STRENGTHCARING

Exons Promoters SNPs Chromosome locus of gene Gene SNPs Haplotypes Causative Site Haplotypes are a code for defining and tracking the isoforms of a gene Gene Haplotypes

Most Detailed Examination of Variability in Human Genes Vol. 293 No July 2001

HAP Technology: The Complete Pharmacogenomic Solution HAP Database –>6,000 genes with 200,000 HAP Markers DecoGen® Informatics System –Links gene variation to drug safety and efficacy HAP Typing Facility –CLIA certified –>2.5M genotypes to date Clinical Genetics Expertise –High-throughput statistical analysis pipeline

Asthma and Albuterol: A Path From Research to Drug Response Diagnostics Research with the Becton Dickinson ProbeTec ET system

Number of Individuals: 119 Mean Value: 13.0 Std. Dev.: RespondersNon- Responders FEV 1 Patient Response to Albuterol Connecting HAP Markers to Breathing Improvement HAP Marker Pairs Associated with Response 4,4 4,2 6,2 2,2 6,4

Proceedings of the National Academy of Sciences vol. 97, no. 19, pp September 12, 2000 First Peer Reviewed Publication Linking Gene Haplotypes and Drug Response

BDProbeTec ET Workflow for Genotyping from Whole Blood Blood in EDTA, Citrate or Heparin Tube Priming Microwells SDA Primers Fluorescent Detectors dNTPs Amplification Microwells Bst Polymerase Enzyme BsoB I Restriction Enzyme Results Universal SDA Buffer Denature and Centrifuge Potential Throughput 96 genotypes 75 min Each subsequent run 45 min Total genotypes per 8 hours = ~1000

STRENGTH I (Statin Response Examined by Genetic HAP Markers) Prospective, multicenter, 3 parallel arms, 2 doses HAP Markers for ~175 genes Clinical Endpoints: –LDL-C responders and non-responders –Changes in HDL-C, LDL/HDL ratios, total C, triglycerides –C-reactive protein, apolipoproteins and other selected measures –Adverse events and baseline lipid and lipoprotein levels

- + % Improvement HDL-CLDL-C ABABCC DRUG Differentiating Statins: Mean HDL and LDL Responses All patients Low Dose

HDL-CLDL-C Differentiating Statins: HAP Marker L40-S1 (26% Frequency) ABABCC DRUG % Improvement All patients L40-S1 (+) Low Dose

HDL-CLDL-C Differentiating Statins: HAP Marker L40-S1 (74% Frequency) ABABCC DRUG All patients % Improvement L40-S1 (-) L40-S1 (+) Low Dose

Conclusions From STRENGTH HAP Markers: Commercialization: Define populations with different response Differentiate between drugs in the same class Can be used to drive market share Statin diagnostic (safety & efficacy) Drug development Drug marketing

Leveraging our Platform DecoGen® Informatics System HAP Database HAP Typing Facility HAP Technology Internal Programs Partnerships Technology Drug- Specific Clinical Genetic Expertise STRENGTHCARING

HAP Technology Partnerships Business Model License fees License fees Service fees for processing clinical samples Service fees for processing clinical samples Success-based milestone payments Success-based milestone payments Drug and diagnostic royalties Drug and diagnostic royalties

Drug-Specific Partnership Collaboration initially focused on Amevive® –moderate to severe chronic plaque psoriasis Marketing-driven strategy –Diagnostic to predict responders & non-responders –justify expensive course of treatment –define new indications Funding and milestones for HAP Marker association studies Royalty on drug sales and testing fee revenues within 2 years

Amevive ® Product Development Timeline March JuneDecemberMarchJuneDecember Planning Phase Define patient groups, select gene list Stage I: Hypothesis Generation Measure genes for markers in patients; Identify 8-10 genes with key markers Stage II: Confirmatory Study Validate markers in separate patient population Optimization and preparation for commercial launch Diagnostic Partner Assay design and development Diagnostic Partner Launch of home brew diagnostic test Diagnostic Partner

Product Development Timelines nd Half1 st Half2 nd Half1 st Half2 nd Half1 st Half2 nd Half CARING Therapeutic HAP Marker Discovery Partner Identifi- cation Phase I & II Phase III Johnson & Johnson Confirmatory Study, Product Development, Marketing Product Launch HAP Marker Discovery Statin Diagnostic Partner Identifi- cation Confirmatory Study, Product Development Product Launch nd Half Confirmatory Study, Product Development Product Launch Biogen: Amevive ® HAP Marker Discovery STRENGTH Therapeutic Partner Identifi- cation Phase I & II Phase III HAP Marker Discovery

Gene Haplotypes and Drug Response Focus on genes and haplotypes Gene specific genome wide approach Technology base fully validated Correlations configured into products Blue-chip partners Growing product portfolio Product launch as early as 2004

From Genomics to Drugs Gene Haplotypes and Drug Response