Th Di i l R dThe Digital Road to Optimum Healthto Optimum Health

Drew Senyei, M.D.e Se yei,Managing DirectorEnterprise Partners Venture Capital

What is “Health”?

“A state of complete physical mentalA state of complete physical mental and social well‐being and not merely the absence of disease or infirmity”the absence of disease or infirmity.  

World Health Organization (1948)Preamble to the Constitution of the World Health Organization as adopted by the International Health Conference, New York, 19‐22 June 1946; signed on 22 July 1947 by the representatives of 61 states

World Health Organization (1948)

Making Progress But Far From “Absence of Disease”

Va i e a e e t a ha dful of di ea e• Vaccines can prevent a handful of diseases• Antibiotics can cure most bacterial infections• Some cancers detected early enough can be cured

• We have greatly improved our longevity– 1950 = 48 years; 2005 = 65.5 yearsy y

– But at the price of more chronic diseases

The Major Determinants of Health

EnvironmentEnvironment

HEALTH LifeHuman HEALTH LifeStyle

Human Biology

Healthcare System

U.S. Healthcare Expenditures An Unsustainable Trend

HealthcareSystem

UnitedStates

%   GDP

%

Source : OECD Health Data 2009

Major Chronic Diseases – Cost US Economy $1.3T Annually for Treatment and Lost Economic Output

HealthcareSystem

An Inconvenient TruthGlobal Fattening

LifeStyle

g

• The major cause of chronic disease morbidity and mortalitymorbidity and mortality– Approaching 20% of healthcare costs 

by 2020 (1)

• A puzzling multi‐factorial etiology– Genes– Environment (toxins viruses)– Environment (toxins, viruses)– Personal behavior

Not ju t i the U S a d ot ju t• Not just in the U.S. and not just people – but also animals that live near us! (2)

(1) Rand Corporation Study(2)Canaries in the Coal Mine; Across species analysis of the plurality of obesity epidemics. Proc. R. Soc.B doc10.1098 (2010)

Progress on Obesity Alone Would Deliver >$100B Cost Savings

The Current Healthcare System Will Not Solve Our Problems

“We cannot solve problems by using the same kind of thinkingusing the same kind of thinking we used when we created them.”

‐Albert EinsteinAlbert Einstein 

Emerging New Tools Can Change Outcomesg

• Predictive Diagnostics g– Better markers of early disease or deviation from health

– Predict individuals response to drugsp g

• Personalized Drugs That Are More Effective– More targeted less side effects and used earlierg

– Applied to Preventing diseases (AIDS chemo phophylaxis)

• Personal longitudinal data and Outcome measurementsg– Healthcare IT needs to move beyond automating current work 

processes to being a “Learning System” that continually improves healthimproves health

Predictive Diagnostics… Not Perfect YetEnvironment

HumanBiology

Genomics

Disease Gene New CasesP Y

Percent With G

Chance of DiDisease Gene Per Year With Gene Disease

Alzheimerʹs ApoE4 380,000 34%‐65% 29%

Breast Cancer

BRCA1,BRCS2 200,000 5%‐10% 36%‐85%

l APC, MLH1,Colon Cancer

APC, MLH1,MSH2, 

MSH6, PMS2145,000 5% 80%‐90%

Source: Modified from Discover Oct. 2006 pg 63

Whole Genome SequencingEnabling Personalized Medicine 

HumanBiology

Genomics

•30,000 WGS by end of 2011•Soon < $1 000 with Clinical Accuracy

‐PREDICTIVE DIAGNOSTICS has begun

•Soon < $1,000 with Clinical Accuracy 

‐DISEASE MECHANISMS being elucidated

‐PERSONALIZED DRUGS on horizon

‐EVERY NEWBORN will be sequenced

Whole Genomic Sequencing Revealing New Disease Mechanisms

HumanBiology

Genomics

For Many Patients Drugs Are Ineffective(1)

Oncology ≅ 30%Oncology ≅ 30%

Migraine ≅ 50%

A ti D t 60%Anti‐Depressant ≅ 60%

Alzheimer ≅ 30%

Asthma ≅ 60%

I ff h h O d h h UIneffective therapies can cause harm. Over 100,000 deaths in the US (6th leading cause)

(1) Spear B. Health ‐ Chiozzi .M., Huff , J., Clinical Trends in Molecular Medicine 2001,5):201‐4

Personalized MedicinesBased on DNA Sequencingq g

Modified from Burrill and  Company

DNA Is Not Necessarily Destiny

Disease concordance in twins relatively low for complex diseasesy p

The Complexity of Living Systems

• Agiven genetic mutation can have different PENETRANCEA given genetic mutation can have different PENETRANCEresulting in different phenotype in genetically identical twins

•Development and ENVIRONMENT greatly influenceDevelopment and ENVIRONMENT greatly influence phenotype

•POLYGENIC traits can be especially complex to understand•POLYGENIC traits can be especially complex to understand

•EPIGENETIC effects can alter gene expression in twins through differential exposure to chemicals environmentalthrough differential exposure to chemicals, environmental toxins, and diet

Systems Biology Deciphering Complexity

Human Biology

p g p y

P

Genomics Stem Cell

P

H

Y

PREDICTIVE DIAGNOSIS

TranscriptomicsSingle Cell 

Stem Cell

Y

SPERSONALIZED 

DRUGS

ProteomicsPhysiome

e

Stem  

I

O

REGENERATIVE MEDICINE

Metabolomics Cell M

E

VACCINES

Systems Biology: Early Results InTargeted Cancer Treatments

HumanBiology

GenomicsStem

Polycythemia Vera (PV)

StemCells

First Drug in Man From Stem Cell Research for Blood Cancers

JAK 2 mutation

Development Status

Entering Final Phase of FDA Testing for Meylofibrosis/PV TargeGen, Inc. (acquired by Sanofi‐Aventis (2010)

Regenerative MedicineEarly But Promising

Stem

HumanBiology

Genomics y g

• Stem Cells

StemCells

– “Disease in a dish” – iPS disease models*– Drug safety testing – Cardiac Toxicity– First human stem cell treatments underwayy

• Gene Therapy– Common Diseases (heart failure)

• Tissue Engineering• Tissue Engineering– Beyond Cosmetics (Bladders)

*A Model for Neuronal Development and Treatment of Rett Syndrome Using Human iPS Cells; Marchetto, M.C. et al ; Cell 143 (2010)

A Paradigm Shift is RequiredTo Impact Healthcare Costs & Outcomes

HealthcareSystem

CURRENT (Reactive)

•Reactive to diseaseFUTURE    (Preventive)

•Preventive

(1)

Healthcare System

•Ineffective drugs

•Fragmented care with 

i i ti

•Predictive

•Personalizedperverse economic incentives

•Non participating •Participatory 

(1) Lee Hood, P4 Medicine Institute for System Biology

Transformation of Medicine to an Information Science

HealthcareSystem

n

The “Learning” Healthcare System

timization

“Value” Based Personalized

Healthcare System

Value Opt

Evidence Based Medicine

Personalized Healthcare

ealth

care V

Trial & Error Medicine

Medicine

H

Medicine Man Genomic Doctor Holistic Healthcare Team

Integration of healthcare R&D and delivery with information technology

A “Learning Healthcare” System Challenge of Integration

HealthcareSystem

IT Technologies Life Science Advances

Reliable Data/EMR

Interoperability

Longitudinal Outcomes

R&D Productivity

Predictive Biomarkers

Personalized Medicines

Imaging Integration Preventive Care

Government Mandates 

Patient Protection & Affordable Care Act

Accountable Care Organizations

Patient Centric

Patient Centric Care

Patient ComplianceAccountable Care Organizations

Holistic Care Co‐ordination

Re‐aligned Incentives in Re‐imbursement

Patient Compliance

The Medical Home

Technology Already Driving Change In Healthcare Delivery Today

HealthcareSystem y y

• Changing Role of Healthcare Providers– Online on Demand Physician Consultationy

• Changing site of care ‐ The Medical Home– Personal Diagnostic Sensors with Wireless Body Networks

• Changing Role of Patients from Passive to Active consumer– Patient centric healthcare system

Patient Centric HealthcareRequires Compliance

Patient centric healthcare COMPLIANCE a very old problem of human nature

•Only 54% of women with insurance get recommended i (84% if li i k i )screening mammograms (84% if clinic @ worksite)

•20‐30% prescriptions never filled

•Only 50% complete prescribed course of drug therapy

•Most never complete exercise fitness plansp p

Changing Consumer Behavior Tough, But… Can Be Doneg

• Seat Belt Laws• Seat Belt Laws

• Smoking Bans

• Dating – Through Social Media & Internet

Changing Incentives Can Change Patient BehaviorHealthcare

System g

• Motivate ParticipationG f i h i i i i ill k– Government payer reforms without patient participation will not work

– Patient Protection & Affordable Care Act (2010) mandates expanded coverage – Non participation results in tax penalty 

• Incentive Based Patient Economics– Reward wellness by differential insurance premiums– Educate on avoidable diseases from smoking and obesity

• Develop Digital Tools to Educate and Monitor the Health of Individuals– Allow access to patients electronic medical records (personal health records)

H di ti i l l t d t id (CHF)– Home diagnostics wirelessly connected to care providers (CHF)– Quantified Self tracking – encourage data collection

Can Congress Make You Buy Broccoli?And Why That’s a Hard Question(1)

“If the federal government can requireIf the federal government can requirepeople to buy insurance in order to keeppremiums affordable, could it also requirepeople to buy baby aspirin or a gymmembership to keep those premiumsaffordable, on the theory that using theseproducts reduces the use of health careservices and thus insurance costs?”services and thus insurance costs?

Federal Patient Protection & Affordable Care Act Debate

(1) W.K.Mariner, G.J. Annas, and L.H.Glantz; NEJM 364:3, Jan. 20, 2011

Technology Enabling Patient Participatory Healthcarep y

• Social NetworksDi Bl t d– Disease Blogs support groups encourage awareness and motivate patients to action

• Quantified Self‐Movement– Wireless Sensors Monitoring Deviation from Healthy 

Status and changing behaviorStatus and changing behavior  – A Flood of Risk Data Imagined and Real

UCSD ‐mDiet

• Patient interpretation and utilization of data a 

UCSD  mDiet

challenge and opportunity

Consumer DNA Testing –A Case Study

•Data by itself does not necessarily change consumer behavior

OutcomeMeasure Baseline Score Follow‐up Score P Value

A iety 35 2+9 6 34 6+10 0 0 80Anxiety 35.2+9.6 34.6+10.0 0.80

Dietary fat intake 16.0+7.9 15.2+7.5 0.89

Exercise 28.6+23.0 28.6+22.9 0.61

Outcome Measures before and after Receipt of Results of Genetic TestingOutcome Measures before and after Receipt of Results of Genetic Testing. (n=2037) (1)

•Actionable data that motivates patient behavioral change is the 

(1) Effect of Direct‐to‐Consumer Genomewide Profiling to Assess Disease Risk. Cinnamon S. Bloss, PhD, Nicholas J. Schork, PhD, and Eric J. Topol, MD. NEJM: 364;6, Feb. 10, 2011

p gHoly Grail 

Healthcare’s Challenge and OpportunityTurning Data into Knowledge

• Data will drive cost effective care• WHO will generate the data• WHO will interpret the data• WHO will own the data

• How will the US compete in the digitally flat world?M di l T i (750 000 A i )• Medical Tourism (750,000 Americans)

• Beijing Genomics (4,000 Employees)

• Tremendous opportunity for academic industrial collaborations especially in the early stages requiring multidisciplinary teamsmultidisciplinary teams

Future Personal Health RecordsThe Hope and Promise of Integrating All Data

Obesity susceptibility Physician Order Form 2020

gene screen

CBC – with Single Cell WBC ProfileWBC Profile

Pancreatic Methylome

3,000 Serum Protein Profile

Video consult –toxicogenomics exposuretoxicogenomics exposure

Systems Check of Quantified Self Sensors

•Analyses deviation from health

•Recommends personalized care options

3D MRI with biomarkers to rule out Alzheimer’s 

p

•Data at physicians fingertips

Optimization of Health

EnvironmentEnvironment

PATIENT Life Human A IEPARTICIPATION

Life StyleHuman Biology StyleHumanBiology

Healthcare SystemHealthcareSystem

“Very nice resume. Leave a sample of your DNA with my secretary.”p y y y

The New Yorker Cartoon