11 copy 2009 PerkinElmercopy 2009 PerkinElmercopy 2009 PerkinElmercopy 2009 PerkinElmer

Buckeye Growth Partners

Solect

Kevin HrusovskyManaging Director BGP Ex - Caliper CEO PerkinElmer President LSTBioForward Vision Summit

Cradle To Grave Health is Personal

22

Buckeye Growth Partners

Buckeye Growth PartnersAgenda

Personalizing Global Health

1

2

3

State of Health

Personalized Health ndash Molecular Revolution

Inspiring Disruptive Innovation ndash Di5

33

Buckeye Growth Partners

Buckeye Growth Partners

Life Expectancy Gains are Slowing

Lifestyle is Undermining Medical Progress

First time in 200 years childrenrsquos life expectancy is shorter than parents

By 2030

1900 2000Birth Year

Life

Exp

ecta

ncy

0

10

20

30

40

50

60

70

80

90

Gains are Plateauing

Cancer kills ~8 myr ~72

Diabetes 350M double

Autism 188 57x

Asthma allergies double

44

Buckeye Growth Partners

Buckeye Growth Partners

Jaring Timmerman 100World record for backstroke

Jiroemon Kimura 115Worldrsquos Oldest Man

Buster Martin 101Marathoner Life Enthusiast

Ruth Frith 100Shot-put gold medalist

Fauja Singh 100Worldrsquos Oldest Marathon Runner

If you live to the age of a hundred you have it made because very few people die past the age of a hundredrdquo - George Burns (1896-1996)

Living Longer and Doing More

Country 100 yrs + Per 100k

China 17800 13

Canada 3795 115

UK 9330 15

France 14994 25

Japan 36376 28

USA 95548 31

55

Buckeye Growth Partners

Buckeye Growth Partners

US Healthcare Poorer Outcomes - Greater Cost

Forbes (March 2013)

$3 trillion wasted year

66

Buckeye Growth Partners

How Safe is US Healthcare

CDC (2003) NHS National Patient Safety Agency amp the Health Foundation (2008)

100000

10000

1000

100

10

11 10 100 1000 10000 100K 1M 10M

Number of encounters for each fatality

Tota

l live

s lo

st p

er y

ear

How safe is Healthcare

Driving in US

Chartered Flights

Healthcare(1 in ~600)

Dangerous(gt11000)

Ultra Safe(lt1100K)

Scheduled Commercial Airlines

European Railroads

Nuclear Power

Chemical Manufacturing

Bungee Jumping

MountainClimbing

More Dangerous than Bungee Jumping

77

Buckeye Growth Partners

Buckeye Growth PartnersldquoOne Size Fits Allrdquo Does not work $1 Trillion Wasted

Adverse drug reactions

4th leading cause of death

Toxicity

Cancer (all types) 25

Alzheimer disease 30

Hepatitis C 47

Osteoporosis 48

Diabetes 57

Asthma 60

Cardiac arrhythmias 60

Schizophrenia 60

Depression 62

0 10 20 30 40 50 60 70

Efficacy

Cost $200B yr

Depression

Schizophrenia

Cardiac arrhythmia

Asthma

Diabetes

Osteoporosis

Hepatitis C

AD

Cancer

38 cancer drugs approved 2000 - 2010Increased toxicity for targeted agents

bull GREATER MORTALITY

bull GREATER MORBIDITY

bull MORE SEVERE ADVERSE EVENTS

88

Buckeye Growth Partners

Buckeye Growth PartnersDrugsrsquo Toxic Side Effects

WarningsUsers may be at a higher risk of Ulcers Amnesia Heart Attack Stroke Enlarged breasts in

men Insomnia

Suicide

Loss of smell amp taste Internal Bleeding Birth Defects Loss of Libido Weight Gain Seizures

99

Buckeye Growth PartnersJapan is Living Longer than US

Life Expectancy

US Health in International Perspective Shorter Lives Poorer Health (2013) Correlation

Death from Noncommunicable Diseases

Life Expectancy at Birth (Men Women)

1010

Buckeye Growth Partners

Buckeye Growth PartnersCancer 1 Killer in the World and Japan

httpwwwjcancerjpenglishcancerinjapan

Japan

1111

Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US

Life Expectancy at Birth (Men Women)

US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)

Energy Consumption per Capita(kg of oil equivalent per capita)

Inverse Correlation

Life Expectancy Energy Consummption

1212

Buckeye Growth Partners

Buckeye Growth PartnersJapan has one of the lowest levels of obesity

httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic

Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar

IndiaChinaJapan

South KoreaItaly

SwedenFrance

NetherlandsPoland

BrazilTurkey

FinlandGermany

RussiaSpain

GreeceIceland

South AfricaChile

CanadaBritain

AustraliaNew ZealandUnited States

Mexico

0 5 10 15 20 25 30

1313

Buckeye Growth Partners

Buckeye Growth PartnersJapan Public Health Centre

Source American Journal of Clinical Nutrition (October 2012)

21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83

Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer

20 of USA caloric intake

1414

Buckeye Growth Partners

Buckeye Growth Partners23 of People are Overweight

Obesity is a global epidemic

Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)

1515

Buckeye Growth Partners

Buckeye Growth PartnersAchieving food addiction is a SCIENCE

70 consumed by Americans is processed food

BLISS POINT = optimal sugar fat amp salt

Use science (eg brain scans) to achieve BLISS POINT

Irony Healthy food is not profitable

1616

Buckeye Growth Partners

Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals

1717

Buckeye Growth Partners

Buckeye Growth Partners

Earth45B years old

Life2B years old

Industrial Revolution 115959 on Dec 31

Humans150000 years old

1800

1B

Growth Assaulting Ecosystems - Earth is Fighting Back

1818

Buckeye Growth Partners

Buckeye Growth Partners

Earth45B years old

Life2B years old

Industrial Revolution 115959 on Dec 31

Humans150000 years old

1800 1930

1B

2B

Growth Assaulting Ecosystems - Earth is Fighting Back

1919

Buckeye Growth Partners

Buckeye Growth Partners

Earth45B years old

Life2B years old

Industrial Revolution 115959 on Dec 31

Humans150000 years old

1800 1930 1960

1B

2B

3B

Growth Assaulting Ecosystems - Earth is Fighting Back

2020

Buckeye Growth Partners

Buckeye Growth Partners

Earth45B years old

Life2B years old

Industrial Revolution 115959 on Dec 31

Humans150000 years old

1800 1930 1960 2011

1B

2B

3B

7B

Growth Assaulting Ecosystems - Earth is Fighting Back

2121

Buckeye Growth Partners

Buckeye Growth Partners

Earth45B years old

Life2B years old

Industrial Revolution 115959 on Dec 31

Humans150000 years old

1800 1930 1960 2011

1B

2B

3B

7B

Growth Assaulting Ecosystems - World is Fighting Back

45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm

25k species go extinctyear 80 countries no forest ndash 52k g wtree

25 trucks of waste for 1 good Super storms

2222

Buckeye Growth Partners

Buckeye Growth Partners

Subsidies Sugarcane

Corn

$

PricesLowered

Subsidies lead to Unintended ConsequencesBuckeye Growth Partners

2323

Buckeye Growth Partners

Buckeye Growth Partners

Sugarcane

Corn

Cows

Salmon

Chicken

Pesticides

Growth Hormones

Antibiotics

Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners

2424

Buckeye Growth Partners

Buckeye Growth Partners

Cows

Salmon

Chicken

Cancer HeartDisease

Diabetes Stroke

Over-StimulatedInsulin Growth Hormone

Omega 6 OverloadHormone Imbalance

Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners

2525

Buckeye Growth Partners

Buckeye Growth Partners

69 year old truck driver Photoaging - Sun exposure

2626

Buckeye Growth Partners

Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale

Obesity amp exerciseEarly puberty

Older pregnancies

Hormones amp Pesticides

Alcohol amp Smoking

2727

Buckeye Growth Partners

Buckeye Growth PartnersPersonalized Medicine

2828

Buckeye Growth Partners

Buckeye Growth PartnersPersonalized Medicine Health

INFORMATICS

2929

Buckeye Growth Partners

Buckeye Growth PartnersAgenda

Revolutionizing amp Personalizing Global Health

1

2

3

State of Health

Personalized Health ndash Molecular Revolution

Inspiring Disruptive Innovation ndash Di5

3030

Buckeye Growth Partners

Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip

Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation

ProbabilityOf Disease

PersonalizedMedical

Intervention

PersonalizedLifestyle

Modification

GenesBiomarkersProteomics

SNPs

EnvironmentalImpacts

Healthier

Longer Lives

Transform Sick Care into Healthcare

3131

Buckeye Growth Partners

Buckeye Growth Partners

GLOBAL HEALTH REVOLUTION

Extend Productive Life Economically

77 100

3232

Buckeye Growth Partners

Take Away Goes Here

Translating Genomics into Precision MedicineStructure of

genomesBiology of genomes

Biology of disease Advancing medicine

1990-2003Human Genome Project

2004-2010

2011-2020

Beyond 2020

Source Nature v470 p204 (2011)

3333

Buckeye Growth Partners

Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies

Nature Reviews in Drug Discovery (May 2013)

3434

Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials

DRUG TARGET COMPANY INDICATION STATUS

Xalkori EML4-ALK NSCLC FDA Approved in 2011

Zalboraf BRAF kinase Melanoma FDA Approved in 2011

Benlysta BLYS Lupus FDA Approved in 2011

Odanacatib Cathepsin K Osteoporosis Stopped early due to success

Atacicept BLYS Receptor Lupus PIIIII

AMG-785 Sclerostin Osteoporosis PIII

LX4211 SGLT1 Diabetes Completed PII showed POC

LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC

Mapatumumab TRAIL-R1 Cancer PII

Apomab TRAIL-R2 Cancer PII

Dulanermin TRAIL Cancer PII

LX-2931 S1P Lyase Rheumatoid Arthritis PII

LX-1033 TPH1 IBS PII

OC-000459 CRTH2 R Asthma PII

DG-041 Prostanoid EPR PAD PII

Source Nat Rev Drug Disc (Jan 2011)

These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug

3535

Buckeye Growth Partners

Buckeye Growth Partners

Propelling personalized medicine through MDx

Profound Growth of Molecular Test Scope and Availability

Source wwwgenetestsorgUpdated as of 942012

Genetic tests for 2748 diseases in 622 CLIA labs in the US

3636

Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety

$2B

$4B

$5B

REQUIRES biomarker test for 26 approved drugs

RECOMMENDS biomarker test for 90 approved drugs

3737

Buckeye Growth Partners

ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010

ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)

Genomics-Enabled Breakthrough for Melanoma

81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment

Precision Medicine Breakthrough

BRAF V600 Test

BEFORE AFTER

+

3838

Buckeye Growth Partners

Buckeye Growth Partners

Dumb Cancers

bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same

pathway

Smart Cancers

bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early

Sledge G ASCO Presidential address 2011

Stupid and Smart Cancers

3939

Buckeye Growth Partners

Buckeye Growth Partners

Gaddy Getz Broad Institute 2011

Lung cancer has high rate of somatic point mutations

4040

Buckeye Growth Partners

Epigenetics

Only 20 of disease linked to germ line

mutations

Science (2010)

Diet

Drugs

Infections

Life-Style

Stress

Radiation

Pollution

Internal Chemical EnvironmentXenobiotics

InflammationPreexisting diseaseLipid peroxidationOxidative stress

Gut flora

Environment Linked to Explosion in Disease

Epidemic of Chronic Disease

Emerging as key link between environment amp NCD epidemic

4141

Buckeye Growth Partners

Buckeye Growth PartnersGene Expression in Monozygotic Twins

Javier and Carlos 6 years old

Anna Marie and Clotilde66 years old

Yellow = concordance

httpwwwpbsorgwgbhnovabodyepigeneticshtml

50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment

4242

Buckeye Growth Partners

Buckeye Growth Partners

WHO estimates 6m deaths from smoking and 06M deaths from SHS

frac14 of SHS deaths are children frac12 are women

Smoking alters methylation patterns in epigenome

20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)

One Billion Smokers Globally

Epigenetic effects of Smoking

seven automated systems

4343

Buckeye Growth PartnersEpigenetic changes in tumor progression

Increased Histone-modification imbalance

Increased frequency of hypermethylation

Decrease in total DNA methylation content

4444

Buckeye Growth Partners

Buckeye Growth Partners

Human Microbiome - ldquoThe Second Human Genomerdquo

Our bodies contain gt100x more unique bacterial genes than human genes

Asthma Atopic dermatitis

Colorectal cancer Kidney stones Periodontitis

Psoriasis

ObesityIrritable bowel disease Crohnrsquos disease

healthy micobiome perturbedhellip

Science Translational Medicine (June 2012)Trends in Genetics (January 2013)

hellipimmune and metabolic disease

ensue

Linked to Human Microbiome

4545

Buckeye Growth Partners

Buckeye Growth Partners

Microbiome Research is Rising Exponentially

Explosive Growth in Microbiome Research Publications since 2003

Nature Biotechnology (April 2013)

4646

Buckeye Growth Partners

Buckeye Growth Partners

Fact or Fallacy

4747

Buckeye Growth Partners

Buckeye Growth Partners

lsquoNeedingrsquo forms the

basis of addictionndash you canrsquot turn it off anymore

4848

Buckeye Growth Partners

Buckeye Growth PartnersFACT -- Defining food addiction

Robert LustigFood Provocateur

4949

Buckeye Growth Partners

Buckeye Growth Partners7 Criteria of Addiction

1

2

3

4

5

6

7

Tolerance ndash need more substance to get the same effect

Withdrawal ndash anxiety depression tremors

Bingeing

Desire or attempts to cut down or quit

Cravings or seeking

Interference with life

Use despite negative consequences

EmotionalTrigger

Guilt Craving

RitualUsing

Addiction Cycle

Addiction = 3+ of 7 criteria defined by the American Psychological Association

5050

Buckeye Growth Partners

Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate

DOPAMINE (neurotransmitter)

LEPTIN

hellipthe result is metabolic disease

Work well when in balance BUT when things go wronghellip

RESISTANCE

RESISTANCE

ADDICTION

INSULIN

5151

Buckeye Growth Partners

Buckeye Growth PartnersAll Calories

Are NOT EqualFood as a Hormone

5252

Buckeye Growth PartnersAll Calories are NOT Created Equal

Proteins require 10-20 times as much energy to digest as fats

Source Science (February 2013)

5353

Buckeye Growth Partners

Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke

The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem

1360 Calories Total

520 Calories from Fat

89 Daily Total Fat (58g)

89 Daily Total Cholesterol (80g)

63 Daily Total Carbohydrate (190g)

24 teaspoons of sugar (95g)

14 the fat as a block of lardhellip

hellipand 12 a cup of sugar

5454

Buckeye Growth PartnersAll Calories are NOT Created Equal

More energy is needed to digest raw foods

Source Science (February 2013)

5555

Buckeye Growth PartnersCooking increases Body Mass Index

Source PNAS (Npvember 2011)

Changes in BMI on sweet potato diets

Raw Whole

Raw Pounded

Cooked Whole Cooked

Pounded

Raw

Cooked

5656

Buckeye Growth PartnersAll Calories are NOT Created Equal

Fruit fiber mitigates most of the negative effects of sugar

Source Science (February 2013)

5757

Buckeye Growth Partners

Buckeye Growth PartnersOur Craving for Sugar has Consequences

The craving for sugar has contributed to the diabetes epidemic

Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D

Extra 150 calday in all food01 boost in T2D

Implies sugar impacting diabetes more

than obesity

5858

Buckeye Growth Partners

The Mediterranean Dietthe Evidence is In

5959

The Mediterranean Diet ndash the Evidence is In

For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial

6060 Confidential

The Mediterranean Diet ndash the Evidence is In

7447 people with CVD risk (but no prior CVD) were split into three groups

Control Group Low Fat diet

Group 1 Mediterranean diet

PLUS given free extra virgin olive oil

Group 2 Mediterranean diet

PLUS given free nuts

6161

Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In

Control GroupLow Fat Diet

Group 1MD + Olive Oil

Group 2MD + Nuts

30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4

YEARS

6262

Buckeye Growth Partners

Buckeye Growth PartnersHormones Determine Our Metabolic Fate

When things are working ldquoproperlyrdquo we maintain a normal healthy weight

David on a Mediterranean Diet

Irsquom full

Leptin (adipose tissue)bull Level LOW

Dopamine (brain)bull Level LOW

Insulin (pancreas)bull Level LOW

6363

Buckeye Growth Partners

Buckeye Growth PartnersWhen Key Players Go Badhellip

Hormone resistance ndash and metabolic disease

David on a High Sugar and Fat Diet

Hungry amp Lazy

KeepEating

Leptin (adipose tissue)bull Level HIGH

Dopamine (brain)bull Level HIGH

Insulin (pancreas)bull Level HIGH

6464

Buckeye Growth Partners

Buckeye Growth PartnersAgenda

Revolutionizing amp Personalizing Global Health

1

2

3

State of Health

Personalized Health - Molecular Revolution

Inspiring Disruptive Innovation ndash Di5

6565

Buckeye Growth Partners

Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5

Capital Transitions

Greater Purpose amp Vision

Governance amp Culture

Market Immersionamp Strategy

Innovation amp Commercialization

6666

Buckeye Growth Partners

Revolutionize Global Health

Innovation Asymptomatic Personalized Sustainability

United Purpose Eradicate Disease - Cancer

6767

Buckeye Growth Partners

Chris Maki is ALL IN

For my three little girls hellip

6868

Buckeye Growth Partners

Buckeye Growth Partners

Chris Allie and Tommy will never be forgottenContributed photo

6969

Buckeye Growth Partners

Buckeye Growth PartnersBridging The Technology Adoption Gap

Win ndash Win

Technology PatientDISEASES

TRANSLATION

Government Hospitals Pharma and Tools

7070

Buckeye Growth Partners

TECHNOLOGY THEMES

Imaging amp Pathology

BiomarkersMdx Cdx

Cellular Systems

Molecular Analysis

BiologicsVaccines

Targeted SmallMolecule

INFORMATICS

Personalized Health

Solect Solar

7171

Buckeye Growth Partners

Buckeye Growth Partners

Need relevant predictive models

Biomarkers are enabling translation

Cancer Cardiac Stroke and Diabetes

Current industry trends

99+ attrition

$1B+ 15 years

Small AnimalCellDNA RNA Protein

HumanTissue

The Challenge Facing Our Customers

In Vitro In Vivo

TRANSLATION

7272

Buckeye Growth Partners

Buckeye Growth Partners

In Vitro In Vivo

Small AnimalCellDNA RNA Protein

HumanTissue

Top Challenge Facing Our Industry

TRANSLATION

7373

Buckeye Growth Partners

Buckeye Growth Partners

Pre-

Clin

ical

C

linic

alGoal

COST OF TESTING

DAT

A Q

UA

LITY

Disruptive Innovation

in vitro to in vivo to human

Small Animal

Cell

DNA RNA Protein

Human

Tissue

Solect Solar

7474

Buckeye Growth Partners

Buckeye Growth PartnersCapturing Value through Hybrid Model

CONFIDENTIAL

7575 Confidential

Unification of 25 Companies

Life Sciences amp Technology

7676

Buckeye Growth Partners

Advances in Sequencing Technology Enable Clinical NGS

Cost Prohibitive

Cost Effective

ldquoCancer will most likely be transformed by next generation sequencingrdquo

Eric Topol The Creative Destruction of Medicine

7777

Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing

Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing

Sample Prep

Informatics

7878

Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications

Food ID

Agrogenomics

Human Genomics

InfectiousDisease

Inherited Disease

Epigenomics

Transcriptomics

Cancer Diagnostics

Parental Testing

PathogenDetection

Dating

Consumer Genomics

Food and Environment

Neonatal Testing

Livestock Breeding

Fishery Mgmt

7979

Buckeye Growth Partners

Geospiza LIMS and OmicsOffice Visualization

NGS Sample Prep Workflow Solutions

LabChip XT bull Automated DNA Fractionation and Sizing

NGS Workstation Post PCR

Isolate Sample

Fragment amp Sizing

Generate Library

Quantify Sample

Sequence Analyze

LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA

NGS Workstation bull Automated High-throughput Sequencing Sample Preparation

Molecular Biology Workstation bull Nucleic Acid Extraction

MBW DS XT GX NGS XT GX NGSW Geospiza

LabChip DS bull UV-Vis DNARNA Quantification

Sequencing Service

Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages

8080

Buckeye Growth PartnersCustomers Partners amp Advocates

AGBT 2012

AGBT 2011

not a comprehensive list over 500 NGS customers

AGBT 2013

8181

Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications

Food ID

Agrogenomics

Human Genomics

InfectiousDisease

Inherited Disease

Epigenomics

Transcriptomics

Cancer Diagnostics

Parental Testing

PathogenDetection

Dating

Consumer Genomics

Food and Environment

Neonatal Testing

Livestock Breeding

Fishery Mgmt

8282

Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR

Early Detection amp Predisposition

Heterogeneity amp Resistance

Combination and Immune therapies

Non-invasive and frequent samples

8383

Buckeye Growth Partners

More Testing with Smaller Samples

NGS Multiplex Assays CTC Imaging

Tumor Section Core Biopsy - FNA Single Cells

More Testing

Smaller Samples

8484

Buckeye Growth Partners

Buckeye Growth Partners

Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution

8585

Buckeye Growth Partners

Buckeye Growth PartnersGenoptix Advancing Precision Medicine

AQUA avoids ~20 ER false negatives

Conventional IHCERPR ~20-40 disagr

Her2 ~20 disagrki67 no standards

Her2

ER

ki67

PR

(4 slides)

Vectra

simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)

PR-(4)

Ki67+(16)

Her2+(100)

(1 slide)

8686

Buckeye Growth Partners

Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)

Pathology today Nearly Impossible to accurately determine of tumor cells

Error rates are 10 ndash 50

8787

Buckeye Growth Partners

Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis

Canrsquot be done visually Hides nuclei and weakly expressing brown stain

But ENABLED with image analysis

8888

Buckeye Growth Partners

Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition

8989

Buckeye Growth Partners

Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)

9090

Buckeye Growth Partners

Buckeye Growth PartnersReliable automated objective accurate scores

ki67 positivity 0

ki67 positivity 64

ki67 positivity 295

ki67 positivity 80

9191

Buckeye Growth Partners

Buckeye Growth Partners

C

BA

D

C

A

B

High AQUALow AQUA

Ki67 Heterogeneity Quantitation

9292

Buckeye Growth Partners

Buckeye Growth Partners

DAPI PhalloidinKi67

KeratinSignaling 1 Signaling 2

Circulating Tumor Cells Detect 1 Cancer 1B Normal cells

MGH ChipRadiology

Takes weeks to detect

Signaling reflects drug response in days

6-color signaling assayVectra

9393

Buckeye Growth Partners

Buckeye Growth PartnersFluorescence-guided surgery example

Color Fluorescence Overlay

bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection

9494

Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications

Food ID

Agrogenomics

Human Genomics

InfectiousDisease

Inherited Disease

Epigenomics

Transcriptomics

Cancer Diagnostics

Parental Testing

PathogenDetection

Dating

Consumer Genomics

Food and Environment

Neonatal Testing

Livestock Breeding

Fishery Mgmt

9595

Buckeye Growth Partners

Buckeye Growth Partners

Tests

55 available tests

Newborn screening global market opportunity

Total

130M births

North Americas

Births

4M births

$125M $750M $1B$125MMarket

Opportunity

6 2

4M births

Rest of World

122M births

Western Europe

30

100Screened 95 45

Assumes ~60 screened Average 10 testschild

9696

Buckeye Growth Partners

Buckeye Growth Partners

Why Autism

9797

Buckeye Growth Partners

Buckeye Growth PartnersAmong the last untapped Dx opportunities

Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children

97

9898

Buckeye Growth Partners

Buckeye Growth Partners

What is Autism

98

9999

Buckeye Growth Partners

Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)

99

Impaired Communication

Impaired Social Interactions

Repetitive Behaviors Restricted Interests

Autism Spectrum Disorders

100100

Buckeye Growth Partners

Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo

100

5 ndash 20 Genetics bull DNA bull Single gene mutations

80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response

SynapDx Testbull Expression of genesbull Multiple sources of evidence

101101

Buckeye Growth Partners

Buckeye Growth PartnersThe Journey is Long amp Time Matters

101

19 months or earlier

Parentsrsquo First Concern

~45 years

Average Age of ASD Diagnosis

Get in line for Evaluation at Center

~35 years

Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010

486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M

102102

Buckeye Growth Partners

Buckeye Growth PartnersEarly Detection Improves Outcomes

ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo

Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011

Every dollar spent on SynapDx testing could save $70

102

103103

Buckeye Growth Partners

Buckeye Growth Partners

80 of children with autism are missed before age three

Visit Pediatrician

Diagnosed before age 3 (2)

= Suspected of Autism Spectrum Disorder (ASD)

= Autism Spectrum Disorder Diagnosis

Missed before age 3(8)

No evaluation before age 3 Referred and evaluated by age 3

104104

Buckeye Growth Partners

Buckeye Growth Partners

SynapDx test could identify 90 of children by age three

Get SynapDx Test

Missed before Age 3(1)

Diagnosed before age 3 (9)

Lower Risk test result Elevated Risk test result

105105

Buckeye Growth Partners

Buckeye Growth Partners

SynapDx Accelerate Time to Diagnosis

105

Autism CenterPediatricianSuspected Patient

Other Specialists Therapists

Wait until high index of suspicion

Precious Time Lost

Today

With SynapDx Test

Autism CenterPediatricianSuspected Patient

ASD Dx

ASD Dx

45 yrs old

2 yrs old

106106

Neonatal Diagnosis in Two Days STAT-Seq

ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine

50 hours to diagnosis for $13500One test ndash 600 rare diseases

CONFIDENTIAL

107107

Buckeye Growth Partners

Buckeye Growth Partners

We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology

From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need

Answers whenever and wherever you need them

108108

Buckeye Growth Partners

Buckeye Growth Partners

Centralized Model of Scientific Research

Strategic Research

Routine

Analysis

ldquoCore Facilityrdquo

Routine

Analysis

109109

Buckeye Growth Partners

Buckeye Growth Partners

The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows

ldquoCore Facilityrdquo

Strategic Research

Small Footprint Simple Operation Robust Adequate

Performance Affordable

Broadest Application Platform

Legacy Mass Spec

Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price

Expansive $24Bnyr Market

Biotechnology amp Medical Research

Pharmaceuticals DiagnosticsAgriculture

110110

Buckeye Growth Partners

Human Health Environmental Health

Side Effects

Dosage

Medicine

Symptoms

Biomarkers

Food Pathogens

Chemicals

Water Safety

Air Quality

Pollution

Exercise Nutrition

My LifePad ndash Integrating Information for Personalized Health

111111

Buckeye Growth Partners

Buckeye Growth Partners

N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive

N-of-Onereg Realizing Precision Medicine

12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly

associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)

25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial

61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of

Herceptin patient in remission nearly 2 years

79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial

(FDA approved thyroid cancer)

N-of-One material confidential Do not distribute

112112

Buckeye Growth Partners

Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries

Pfizer Sutent (sunitinib)(kidney and stomach cancer)

Pfizer Lyrica (pregabalin)(HIV)

Pfizer Celsentri (maraviroc)(neuropathic pain)

Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)

Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)

Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)

Takeda Rozerem (ramelteon)(sleep disorders)

BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)

SIRTex SIR-Spheres (yttrium-90)(liver cancer)

Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)

Phase I

Cell Genesys CG0070 (Bladder and multiple indications)

Nereus Pharma NPI-0052 (multiple myeloma)

Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)

Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)

Insert Therapeutics IT101 (solid tumors)

Novartis CHIR-258 (Metastatic melanoma)

Novartis AEE788 (Advanced Cancers)

Phase IIIII

Sanofi-Aventis Aflibercept (Multiple indications)

Boehringer Ingelheim Oldodaterol (COPD)

Xencor XmAb2513 (Hodgkinrsquos Lymphoma)

Neurogen DAB-452 (Parkinson)

EntreMed Panzem (Recurrent Glioblastoma)

FDA Approved In Clinical Trials

113113

Buckeye Growth Partners

Buckeye Growth PartnersAgenda

Personalizing Global Health

1

2

3

State of Health

Personalized Health ndash Molecular Revolution

Inspiring Disruptive Innovation ndash Di5

114114

Buckeye Growth Partners

Buckeye Growth PartnersThank You BioForward Vision Team andhellip

Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures

Buckeye Growth Partners

Solect Solar