The Era Of Genomic Medicine…

What to expect

Ronnie Andrews

President, Medical Sciences

The Medical Diagnostics World Begins & Ends With a

Patient/Physician Encounter

Therapy Selection

Prognosis Diagnosis Screening

Biopsy

Primary Care / Specialists Pathology Oncology Pr imary Care / Oncology

Morphology

H&E IHC Fish Pathology Data

Bioformational

Synthesis

Physician

Dashboard

Cells

Selected

Recurrence Monitoring

Therapy Monitoring

Sample

Prep Genomic

Analysis qPCR

Confirmation

Can We Expect History to Repeat Itself?

Clinical

Chemistry

1970

1980

1990

1990

Microbiology

1970

1980

1990

1995

Immuno

Chemistry

1980

1985

1990

1990

Automated

Blood

Banking

1990

1995

2000

2005

Molecular

Dx

1998

2000

2005

TBD

NGS

2012

TBD

As complexity of disease is better understood, and Therapeutic

Monitoring of Targeted Rx becomes a reality, the race to

democratize NGS will increase.

Translational Medicine Today When all else has failed and outcome is binary…

• Genomic information is identifying intervention points for treatment

• Off label attempts to save the patient are emerging

• Successes based on “pathway treatment approach” are becoming more prevalent

Understanding Variation and Its Link to Disease or Response

Evolving Model Driven By Therapeutic Availability

A Collision Course with Complexity

• 500 compounds on the way

• Targeting more than 100 biomarkers

• $6 million & 2 years to develop each

• Multiple Dx tests for each marker

Today’s Model is Unsustainable

Hospital

Reference Lab

Esoteric Lab

Pharma (CRO)

Sample

1

Cost - $1,000

Days - 5

Cost - $2,500

Days - 5

Cost - $4,000

Days - 15

Cost - $0

Days - 15

Sample 2

Sample

3

Sample

4 “Where do I go for

what test and

what do I do with

the information?”

Total Cost ~$7,500

Patient Health

Total Days 40

The Promise of Next Generation Sequencing

Sequencing-Guided Medicine Optimal Therapy Selection

PTEN+

KRAS-

• Profile hundreds of genes at once

• Price comparable to individual Dx tests

• Fast turnaround time

• Easily incorporate new genes as clinical

science advances

Anatomic

Classification

Genomic

Classification

Moore’s Law

$3B

$5K

1999 2011 2005

Cost to

sequence

genome

Clinical

Value

Co

st

Pe

r G

en

om

e In

form

atio

n V

alu

e

Pathologist’s Opportunity…Information Synthesis

Real Time Access To Comparative Information

Becomes Pathologist’s Tool

GCI Software

GCI Data

System

Interpreting physician

Variants

Treating physician

Knowledge apps Treatment

& Outcomes

Health

Info:

Treatment

& Outcomes

Sequence Data

Genomic data

Page 11

Single service order:

1) Tissue profiling (multiplex staining)

2) NGS Exome – Genome performed (variants,

expression profile, structural variation, epigenetics)

3) Utilize informatics tools to query against knowledge

base

4) Follow Rules-Based Treatment guidelines to select

treatment (combination cocktail) based on marker

pattern

CT screen /PET

scan identifies

suspicious lung

mass

Doctor

receives

treatment

guidance

Personalized

treatment

prescribed

Doctor Orders Molecular

Medicine 2.0 Services

!

Tissue biopsy

performed

Evidence Based Informatics Will Allow Maturation

of Clinical Care

How One Man Sees The Future…

Page 12

Deeper understanding of biological pathways drives confidence

in treatment recommendations

Growing number of patients benefiting from diagnostics that

repurpose existing and emerging therapies in combination with

standard of care

Access to targeted population-based medicine supports patient-

centric decisions through more targeted therapeutic

interventions

Less invasive monitoring – personalized, using Individual

Molecular Signatures (IMS)

Molecular Medicine 1.0 (0- 3 Years) (New Biomarkers Driving Biological Interpretation)

Molecular Medicine 2.0 (3-5 Years) (Rules-Based Approaches to Individualized Treatment)

The Initial Offering From Path Labs

Targeted

Molecular

Analysis

Panels based

on actionability

(RUO device)

Variant List,

Protein

Profiles

Database

query:

Pathway

correlation

Pertinent

Perturbed

Pathways

List

Database

query: Drug/

pathway

interactions

Patient

sees her

oncologist,

gets new

tumor

biopsy

Treatment

Options

Therapy

Options:

Combinations,

Side effects,

PGx, Cost, etc.

Confirmation

of Variants as

a basis of

intervention

(CLIA/ FDA

Device)

Treatment

Preference

Treatment

Prescribed

Patient’s response entered into database to

further refine gene-to-treatment algorithm for

other patients

Page 13

!

Expert

Intermediary

“Molecular

Physician”

Aspirational Care Model 4-7 years

Page 14

Molecular Medicine 3.0

(Rules-based treatment)

Patient now understands how her cancer is different and her

physician is making personalized decisions to help manage her

chronic disease

Molecular data from multiple biomarker types has been integrated

to inform patient options

Many more targeted drugs are available, with selection supported

by “rules” established in smaller targeted clinical studies

Real Time query of annotated database allows for comparative

medicine approach to ensure the best treatment protocol specific to

the patient

Individual Molecular Signatures (IMS) developed at diagnosis

Personalized, less invasive disease monitoring

Wellness metric

H&E

Molecular Pathologist :

Specimen procurement

Tissue Processing

Embedding / Cutting / Cover Slipping

Laser Capture

Microdissection

Future integrator of molecular interrogation of tissue

Tissue Prep for Molecular Sequencing

Integrated Pathology Workstation

(Digital path to enable data integration with

molecular)

IHC

PGM

Slides

Tissue

SS

ISH

Today’s AP Lab

Future AP Lab

Phenotypic analysis

Genotypic analysis

Medical database

Experiential database

Tissue Prep and Primary

Staining Primary

Staining

Advanced Staining Microscope

Digital Path

Synthesis Engines Will Allow For Critical Queries

1. Which

alterations are

seen in similar

patients as

mine?

Treating

Physician

Patient Clinical

Information • Role-based workflow

and user interface

• Interpretation of routine

assays

• Interface w/

Annotated/Curated

databases and

analytical tools

• Reporting

• Security, audit,

archive…

Ion Reporter

Interpreting

Physician

2. Which are likely

drivers vs.

passenger

mutations in my

patient?

3. Are the driver

mutations for my

patient pointing to

specific actionable

targets?

4. What is the

clinical evidence

for response to

the specific

targets I am

considering for

my patient?

Torrent Suite

Sequencer

Sequence

Exomes

Genomes

Variants

Report

A

B A

B

EGFR Pathway Disrupted

The Interpreting Physician Cockpit

7 GE Title or job number

7/13/2011

The Plan

• Drive Patient-focused

decisions – Treating your

disease, not a disease

• Convergence and integration

of Life Science and Dx

technologies

• Develop Bioinformatics to

attach lifelong health data to

patient and deliver

comprehensive patient

information for better

decision making

• Capitalize on the exponential

expansion of the Molecular

Diagnostics market

12 GE Title or job number

7/13/2011

Key Segment: Molecular Diagnostics

Precise therapy

requires precise

diagnostics

The way we look at disease is changing Assembling the necessary technologies

to lead

Responders

Patient populations

Mammography Molecular Biopsy Tools

Tumor

+

IHC Stain

Gene sequencing Molecular pathology

Imaging Molecular Diagnostics

Alzheimer’s Disease Age matched control

[18F]AH110690 PET Imaging

90 –120 min summation

Alzheimer’s Disease Age matched control

[18F]AH110690 PET Imaging

90 –120 min summation

Operations &

commercialization

Molecular imaging

agents & equipment

Technology &

content

Enabling

workflow

in vivo

diagnostics

GRC

Molecular

Pathology

Digital

Pathology

Clarient

Molecular profiling segment for cancer expected to

grow from $15B in 2010 to $47B in 2015

... to be a leader in the next diagnostic

frontier

Toxic

impact

No

impact

Driving toward a patient-centric, technology-agnostic vision of the future requires

use of multiple biomarker types, access to comparative medicine database and

clinical judgment

The Treating Physician Portal

• Allows real time access to patient

information and education to drive

better management of complex

diseases

Decentralizing NGS Empowers Community Practitioners

• Practice research medicine

• Create content

• Validate utility

• Drive standard of care

• Research flexibility

• Non-regulated OK

• Bio-Informatic solutions w/

flexible algorithms

• Fast followers

• Assertive/Competitive

• Want to "Look Like" 1%

• Sophisticated workforce

• Regulated needs

• Fixed algorithms

• Support Local community with high

level of care

• Center of Excellence for monitoring

• Automated

• Sophisticated workflows

• Fixed algorithms

• High level tech support

• Advanced informatics & reporting

• IVD Requirement

Attributes System Needs <200

<500

>2,000

>3,000

Democratization Of NGS Will Happen

Clinical

Chemistry

1970

1980

1990

1990

Microbiology

1970

1980

1990

1995

Immuno

Chemistry

1980

1985

1990

1990

Automated

Blood

Banking

1990

1995

2000

2005

Molecular

Dx

1998

2000

2005

TBD

NGS

2012

Large and Medium Sized Hospital Labs Should Begin

Preparation to Become Molecular Labs and Embrace Their Role

in Bringing Personalized Medicine to the Community!

2020

2014

2015

Semiconductors Disrupt Industries

21

Transformative Technology, Unprecedented Progress Scalable Semiconductor Technology plus Simple Chemistry

Wafer Semiconductor Manufacturing

Chip Semiconductor Packaging

Millions of Sensors Semiconductor Design

Sensor Plate

Silicon Substrate

Drain Source Bulk

∆ pH

∆ V

Sensing Layer

H+

Single Sensor Chemical to Digital Sequence

TCGTACC…

Ion Semiconductor Sequencing Rapid, bench top sequencing for all

23 The content provided herein may relate to products that have not

been officially released and is subject to change without notice.

Headwinds To Success

• Access to archived patient cohorts

• Increased Regulatory Oversight/Complexity

• Lack of understanding on how to effectively

reimburse for MolDx

• Payors resisting paying for therapeutics “off label”

• Technology ease of use

• No focused didactic training around molecular

pathology (need “Interpreting Physician”)

Our Call To Action

• Embrace the change…a chance to elevate

laboratory medicine to an integral function in

disease management

• Let your voice count…become active in industry

associations to educate and promote the

acceptance of MolDx by payors and regulators

• Focus on the Patient…the next 10 years

represent a major tipping point for solving complex

diseases

Far and away the best prize that life offers is

the chance to work hard at work worth doing

Theodore Roosevelt

Q&A