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

From Genomics to From Genomics to Drugs Drugs

Kitasato University – Kitasato University – Harvard School of Public Harvard School of Public Health SymposiumHealth Symposium

Kevin RakinKevin Rakin

President & CEOPresident & CEO

Genaissance TodayGenaissance Today

Our Focus:Our Focus:Drug response Drug response

Our Approach:Our Approach:Integrating gene variation into Integrating gene variation into product development and drug product development and drug marketingmarketing

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Drug Response

The Genaissance Drug ParadigmThe Genaissance Drug Paradigm

HAP™ Technology shifts the drug response curve Safer and more effective prescriptions Ability to move market share

ConventionalConventionalDrugsDrugs

HAPHAP™ Technology ™ Technology Guided DrugsGuided Drugs

Leveraging our PlatformLeveraging our Platform

DecoGen® Informatics

System

HAP™Database

HAP™ Typing Facility

HAP™ Technology

Internal Programs

Partnerships

TechnologyDrug-

Specific

Clinical Genetic

Expertise

STRENGTH CARING

Exons

Promoters

SNPs

Chromosomelocus of gene

Gene SNPs01

01

01

01

01

Haplotypes0 1 0 0 1

1 0 1 1 0

Causative Site

Haplotypes are a code for defining and tracking the isoforms of a gene

Gene HaplotypesGene Haplotypes

Most Detailed Examination of Variability in Most Detailed Examination of Variability in Human GenesHuman Genes

Vol. 293 No. 552920 July 2001

HAP™ HAP™ Technology: Technology: The Complete Pharmacogenomic SolutionThe 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

Number of Individuals: 119Mean Value: 13.0Std. Dev.: 8.0

-5.0 10.0 25.0 40.0 55.0

RespondersNon-Responders

0

20

18

16

14

12

10

8

6

4

2

FEVFEV11 Patient Patient Response toResponse toAlbuterolAlbuterol

Connecting Connecting HAPHAP™ Markers to ™ Markers to Breathing ImprovementBreathing Improvement

HAPHAP™ Marker ™ Marker Pairs Pairs Associated with Associated with ResponseResponse

4,44,4 4,26,24,26,2

2,22,2 6,46,4

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciencesvol. 97, no. 19, pp. 10483-10488

September 12, 2000

First Peer Reviewed Publication LinkingFirst Peer Reviewed Publication LinkingGene Haplotypes and Drug ResponseGene Haplotypes and Drug Response

BDProbeTec™ ET Workflow for BDProbeTec™ ET Workflow for Genotyping from Whole BloodGenotyping from Whole Blood

Blood in EDTA, Citrate or Heparin

Tube

Priming Microwells• SDA Primers• Fluorescent Detectors• dNTPs

Amplification Microwells • Bst Polymerase Enzyme• BsoBI Restriction Enzyme

Results

UniversalSDA Buffer

Denature and Centrifuge

Potential Throughput96 genotypes 75 minEach subsequent run 45 minTotal genotypes per 8 hours = ~1000

STRENGTH I(Statin Response Examined by Genetic HAP™ Markers)

Prospective, multicenter, 3 parallel arms, 2 dosesProspective, multicenter, 3 parallel arms, 2 doses

HAPHAP™ Markers for ~175 genes™ Markers for ~175 genes

Clinical Endpoints:Clinical Endpoints:

– LDL-C responders and non-responders LDL-C responders and non-responders

– Changes in HDL-C, LDL/HDL ratios,Changes in HDL-C, LDL/HDL ratios,total C, triglycerides total C, triglycerides

– C-reactive protein, apolipoproteinsC-reactive protein, apolipoproteinsand other selected measuresand other selected measures

– Adverse events and baseline lipidAdverse events and baseline lipidand lipoprotein levelsand lipoprotein levels

-

+

% I

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0

+

% I

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rove

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HDL-C LDL-C

A B A BC CDRUG DRUG

Differentiating Statins:Differentiating Statins:Mean HDL and LDL ResponsesMean HDL and LDL Responses

All patients

Low Dose

-

+

0

+

0

HDL-C LDL-C

Differentiating Statins: Differentiating Statins: HAPHAP™ Marker L40-S1 ™ Marker L40-S1 ((26% Frequency26% Frequency))

A B A BC CDRUG DRUG

% I

mp

rove

men

t

% I

mp

rove

men

t

All patientsL40-S1 (+)

Low Dose

-

+

0

+

0

HDL-C LDL-C

Differentiating Statins: Differentiating Statins: HAPHAP™ Marker L40-S1™ Marker L40-S1((74% Frequency74% Frequency))

A B A BC CDRUG DRUG

All patients

% I

mp

rove

men

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% I

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L40-S1 (-)L40-S1 (+)

Low Dose

Conclusions From STRENGTHConclusions 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 PlatformLeveraging our Platform

DecoGen® Informatics

System

HAP™Database

HAP™ Typing Facility

HAP™ Technology

Internal Programs

Partnerships

TechnologyDrug-

Specific

Clinical Genetic

Expertise

STRENGTH CARING

HAP™HAP™ Technology Partnerships Technology Partnerships

Business ModelBusiness Model

License fees License fees Service fees for processing clinical samples Service fees for processing clinical samples Success-based milestone paymentsSuccess-based milestone payments Drug and diagnostic royaltiesDrug and diagnostic royalties

Drug-Specific PartnershipDrug-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

AmeviveAmevive®® Product Development TimelineProduct Development Timeline

March June December March June December

2002 2003

Planning Planning PhasePhase

Define patient groups, select gene list

Stage I:Stage I:HypothesisHypothesisGenerationGeneration

Measure 25-100 genes for markers in patients; Identify 8-10 genes with key markers

Stage II:Stage II:ConfirmatoryConfirmatoryStudyStudy

Validate markers in separate patient population

Optimization Optimization and preparation and preparation for commercial for commercial launchlaunch

Diagnostic Partner

Assay design and Assay design and developmentdevelopment

Diagnostic Partner

Launch of home Launch of home brew diagnostic brew diagnostic testtest

Diagnostic Partner

Product Development TimelinesProduct Development Timelines

2002 2003 2004 20052nd Half 1st Half 2nd Half 1st Half 2nd Half 1st Half 2nd Half

CARING Therapeutic

HAP™ MarkerDiscovery

Partner Partner Identifi-Identifi-cationcation

Phase I & IIPhase I & II Phase IIIPhase III

Johnson& Johnson

Confirmatory Study,Confirmatory Study,Product Development, MarketingProduct Development, Marketing

ProductProductLaunchLaunch

HAP™ Marker

Discovery

Statin DiagnosticPartner Partner Identifi-Identifi-cationcation

Confirmatory Study, Confirmatory Study, Product DevelopmentProduct Development

ProductProductLaunchLaunch

20062nd Half

Confirmatory Study,Confirmatory Study,ProductProduct

DevelopmentDevelopment

ProductProductLaunchLaunch

Biogen:Amevive®

HAP™ Marker

Discovery

STRENGTHTherapeutic

Partner Partner Identifi-Identifi-cationcation

Phase I & IIPhase I & II Phase IIIPhase IIIHAP™ Marker

Discovery

Gene Haplotypes and Drug ResponseGene 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 From Genomics to Drugsto Drugs

Gene Haplotypes Gene Haplotypes and Drug Responseand Drug Response