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From Genomics to
Drugs
Kitasato University –
Harvard School of Public
Health Symposium
Kevin Rakin
President & CEO
Genaissance Today
Our Approach:
Integrating gene variation into
product development and drug
marketing
Our Focus:
Drug response
GNSC
The Genaissance Drug Paradigm
HAP™ Technology shifts the drug response curve
 Safer and more effective prescriptions
 Ability to move market share
Number of
Patients
HAP™ Technology
Guided Drugs
Conventional
Drugs
Drug Response
Leveraging our Platform
HAP™ Technology
HAP™
Database
DecoGen®
Informatics
System
Partnerships
Technology
DrugSpecific
HAP™ Typing
Facility
Clinical
Genetic
Expertise
Internal
Programs
STRENGTH
CARING
Gene Haplotypes
Exons
Chromosome
locus of gene
Promoters
SNPs
0
Gene SNPs 1
0
1
0
1
0
1
0
1
0
1
0
0
1
1
0
1
1
0
Haplotypes
Causative
Site
Haplotypes are a code for defining
and tracking the isoforms of a gene
Most Detailed Examination of Variability in
Human Genes
Vol. 293
No. 5529
20 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
Connecting HAP™ Markers to
Breathing Improvement
Number of Individuals:
119
Mean Value: 13.0
Std. Dev.: 8.0
20
18
16
FEV1 Patient
Response to
Albuterol
14
HAP™ Marker
Pairs
Associated with
Response
12
10
8
6
4
2
0
-5.0
4,4
10.0
NonResponders
4,2
6,2
25.0
2,2
40.0
55.0
Responders
6,4
First Peer Reviewed Publication Linking
Gene Haplotypes and Drug Response
Proceedings of the National
Academy of Sciences
vol. 97, no. 19, pp. 10483-10488
September 12, 2000
BDProbeTec™ ET Workflow for
Genotyping from Whole Blood
Blood in EDTA,
Citrate or Heparin
Tube
Universal
SDA Buffer
Priming Microwells
Denature and
Centrifuge
Potential Throughput
96 genotypes  75 min
Each subsequent run  45 min
Total genotypes per 8 hours = ~1000
• SDA Primers
• Fluorescent Detectors
• dNTPs
Amplification Microwells
• Bst Polymerase Enzyme
• BsoBI Restriction Enzyme
Results
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
Differentiating Statins:
Mean HDL and LDL Responses
+
+
% Improvement
LDL-C
% Improvement
HDL-C
0
DRUG
0
A
B
C
DRUG
A
B
C
All patients
Low Dose
Differentiating Statins: HAP™ Marker L40-S1
(26% Frequency)
+
+
% Improvement
LDL-C
% Improvement
HDL-C
0
DRUG
0
A
B
C
DRUG
All patients
L40-S1 (+)
A
B
C
Low Dose
Differentiating Statins: HAP™ Marker L40-S1
(74% Frequency)
+
+
% Improvement
LDL-C
% Improvement
HDL-C
0
DRUG
0
A
B
C
DRUG
All patients
L40-S1 (+)
L40-S1 (-)
A
B
C
Low Dose
Conclusions From STRENGTH
HAP™ Markers:
• Define populations with different response
• Differentiate between drugs in the same class
• Can be used to drive market share
Commercialization:
• Statin diagnostic (safety & efficacy)
• Drug development
• Drug marketing
Leveraging our Platform
HAP™ Technology
HAP™
Database
DecoGen®
Informatics
System
Partnerships
Technology
DrugSpecific
HAP™ Typing
Facility
Clinical
Genetic
Expertise
Internal
Programs
STRENGTH
CARING
HAP™ Technology Partnerships
Business Model
 License fees
 Service fees for processing clinical samples
 Success-based milestone payments
 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
2002
June
March
2003
December
March
June
December
Planning
Phase
Define patient
groups, select
gene list
Stage I:
Hypothesis
Generation
Measure 25-100
genes for
markers in
patients; Identify
8-10 genes with
key markers
Stage II:
Confirmatory
Study
Optimization
and preparation
for commercial
launch
Diagnostic Partner
Validate markers in
separate patient
population
Diagnostic Partner
Assay design and
development
Launch of home
brew diagnostic
test
Diagnostic Partner
Product Development Timelines
2002
2nd Half
Biogen:
Amevive®
Johnson
& Johnson
Statin Diagnostic
STRENGTH
Therapeutic
CARING
Therapeutic
2003
1st Half
2004
2nd Half
1st Half
2nd Half
2005
1st Half
2nd Half
Confirmatory Study,
HAP™
Product
Marker
Product
Launch
Discovery
Development
HAP™
Marker
Discovery
Partner
Identification
HAP™
Marker
Discovery
Confirmatory Study,
Product Development, Marketing
Confirmatory Study,
Product Development
Partner
Identification
HAP™ Marker
Discovery
Product
Launch
Phase I & II
Partner
Identification
Product
Launch
Phase I & II
Phase III
Phase III
2006
2nd Half
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