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
GNSCGNSC
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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
mp
rove
men
t
0
+
% I
mp
rove
men
t0
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
t
% I
mp
rove
men
t
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