Kevin Hrusovsky, Former CEO and President of Caliper Life Science and President of PerkinElmer's Life Sciences and Technology group will tackle the current global state of healthcare and will deliver a framework for inciting a global health revolution. He will also discuss how disruptive technologies are enabling personalized health - Cradle to Grave.
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Life Expectancy Gains are Slowing
Lifestyle is Undermining Medical Progress
First time in 200 years, children’s life expectancy is shorter than parents
By 2030
1900 2000Birth Year
LifeExpectancy
0
10
20
30
40
50
60
70
80
90
Gains are Plateauing
Cancer kills
~8 m/yr: ~72%
Diabetes 350M:
double
Autism 1/88:
57x
Asthma /
allergies: double
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Jaring Timmerman, 100
World record for backstroke
Jiroemon Kimura, 115
World’s Oldest Man
Buster Martin, 101
Marathoner, Life Enthusiast
Ruth Frith, 100
Shot-put gold medalist
Fauja Singh, 100
World’s 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 hundred.” - George Burns (1896-1996)
Living Longer and Doing More
Country 100 yrs + Per 100k
China 17,800 1.3
Canada 3,795 11.5
UK 9,330 15
France 14,994 25
Japan 36,376 28
USA 95,548 31
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How Safe is US Healthcare?
CDC (2003); NHS National Patient Safety Agency & the Health Foundation (2008)
100,000
10,000
1,000
100
10
1
1 10 100 1,000 10,000 100K 1M 10M
Number of encounters for each fatality
Totalliveslostperyear
How safe is Healthcare?
Driving
in US
Chartered
Flights
Healthcare
(1 in ~600)
Dangerous
(>1/1,000)
Ultra Safe
(<1/100K)
Scheduled
Commercial
Airlines
European
Railroads
Nuclear
Power
Chemical
Manufacturing
Bungee
Jumping
Mountain
Climbing
More Dangerous than Bungee Jumping!
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Partners“One Size Fits All” 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 - 2010
Increased toxicity for targeted agents
• GREATER MORTALITY
• GREATER MORBIDITY
• MORE SEVERE ADVERSE EVENTS
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Buckeye
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Warnings
Users may be at a higher risk of
Ulcers
Amnesia
Heart Attack
Stroke
Enlarged breasts in
men
Insomnia
Suicide
Loss of smell & taste
Internal Bleeding
Birth Defects
Loss of Libido
Weight Gain
Seizures
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Life Expectancy
U.S. Health in International Perspective: Shorter Lives, Poorer Health (2013) Correlation
Death from Noncommunicable Diseases
Life Expectancy at Birth
(Men, Women)
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Life Expectancy at Birth
(Men, Women)
U.S. 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
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http://steadfastfinances.com/blog/2010/09/23/global-obesity-rates-making-money-on-the-obesity-epidemic/
Japan has 8x lower rates of obesity than
the USA and consumes 10x less sugar
0 5 10 15 20 25 30
India
China
Japan
South Korea
Italy
Sweden
France
Netherlands
Poland
Brazil
Turkey
Finland
Germany
Russia
Spain
Greece
Iceland
South Africa
Chile
Canada
Britain
Australia
New Zealand
United States
Mexico
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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
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Earth
4.5B years old
Life
2B years old
Industrial Revolution; 11:59:59 on Dec 31
Humans
150,000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back!
4.5B years of stored fossil fuel Greenhouse gas = 400 vs. 250ppm
25k species go extinct/year 80 countries no forest – 52k g w/tree
25 trucks of waste for 1 good Super storms
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Take Away Goes Here
Translating Genomics into Precision Medicine
Structure of
genomes
Biology of
genomes
Biology of
disease Advancing medicine
1990-2003
Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source: Nature v.470, p.204 (2011)
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Buckeye
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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 PII/III
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 data
This is the tip of the iceberg, since it takes 10-15 years to develop a drug
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“A major breakthrough in metastatic melanoma
treatment.”
NEJM Editorial, August 26, 2010
“We have never seen 80% response rate in
melanoma. This is remarkable.”
Paul Chapman, M.D., 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
+
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Dumb Cancers
• Single dominant mutation
• Small mutation load
• Monotherapy is effective
• Resistance rare, late, same
pathway
Smart Cancers
• Multiple mutational divers
• Large mutational load
• Multi-targeted therapy required
• Resistance common, early
Sledge, G. ASCO Presidential address, 2011
Stupid and Smart Cancers
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Epigenetics
Only 20% of disease
linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical
Environment
Xenobiotics
Inflammation
Preexisting disease
Lipid peroxidation
Oxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between
environment & NCD epidemic
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Buckeye
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Javier and Carlos
6 years old
Anna Marie and Clotilde
66 years old
Yellow = concordance
http://www.pbs.org/wgbh/nova/body/epigenetics.html
50k Person Sister & Epi-Twin Studies
70+% of Health linked to Environment
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WHO estimates 6m deaths
from smoking and 0.6M
deaths from SHS
¼ of SHS deaths are children,
½ are women
Smoking alters methylation
patterns in epigenome
20 year - 40,000 patient study to examine effects of
direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
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Human Microbiome - “The Second Human Genome”
Our bodies contain >100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
Obesity
Irritable bowel disease Crohn’s disease
healthy micobiome
perturbed…
Science Translational Medicine (June 2012)
Trends in Genetics (January 2013)
…immune and
metabolic disease
ensue
Linked to Human Microbiome
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Buckeye
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1
2
3
4
5
6
7
Tolerance – need more substance to get the same effect
Withdrawal – anxiety, depression, tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
Emotional
Trigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
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Buckeye
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PartnersA Big Mac, Large French Fries & Large Coke
The “typical” 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)
1/4 the fat as a block of lard… …and 1/2 a cup of sugar
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Buckeye
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The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries shows:
Extra 150 cal/day in sugar 1.1% boost in T2D
Extra 150 cal/day in all food0.1% boost in T2D
Implies sugar impacting diabetes more
than obesity
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The Mediterranean Diet – the Evidence is In!
For the first time ever, the protective
effect of the Mediterranean Diet was
examined in a large, randomized trial.
60. 6060 Confidential
The Mediterranean Diet – the Evidence is In!
7,447 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
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Control Group
Low Fat Diet
Group 1
MD + Olive Oil
Group 2
MD + Nuts
30% LESS LIKELY TO HAVE
SUFFERED A CVD EVENT – AFTER 4
YEARS
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Buckeye
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When things are working “properly” we maintain a normal healthy weight
David on a
Mediterranean Diet
I’m full
Leptin (adipose tissue)
• Level: LOW
Dopamine (brain)
• Level: LOW
Insulin (pancreas)
• Level: LOW
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Hormone resistance – and metabolic disease
David on a High
Sugar and Fat Diet
Hungry & Lazy
Keep
Eating
Leptin (adipose tissue)
• Level: HIGH
Dopamine (brain)
• Level: HIGH
Insulin (pancreas)
• Level: HIGH
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Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
“Cancer will most likely be transformed by next
generation sequencing.”
Eric Topol, The Creative Destruction of Medicine
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Key Bottlenecks in Next Generation Sequencing
Source: The Global Outlook for Next Generation Sequencing: Usage, Platform Drivers & Workflow (2011) BioInformatics LLC.
Survey asking 267 scientists currently using Next Generation Sequencing.
Sample Prep
Informatics
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Buckeye
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Food ID
Agrogenomics
Human Genomics
Infectious
Disease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
Pathogen
Detection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock
Breeding
Fishery Mgmt
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Buckeye
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PartnersNo Easy Answer to “What Causes Autism?”
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5 – 20% Genetics
• DNA
• Single gene mutations
80% Unexplained
• Environmental?
• Age of the father?
• Events during pregnancy?
• Immune response?
SynapDx Test
• Expression of genes
• Multiple sources of evidence
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Buckeye
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19 months or earlier
Parents’
First Concern
~4.5 years
Average Age of ASD
Diagnosis
Get in line for Evaluation
at Center
~3.5 years
Source: www.cdc.gov, www.iancommunity.org; SynapDx Parent Survey Sept 2010
486,000 children suspected of developmental delay annually in US
A third of patients get diagnosed at autism centers
50,000 diagnosed with ASD annually
Lifetime costs per ASD patient $3.2M
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Buckeye
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“20% of children have the autism label removed when
behavioral therapy is begun early.”
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
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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
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SynapDx: Accelerate Time to Diagnosis
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Autism CenterPediatrician
Suspected Patient
Other Specialists / Therapists
Wait until high index of
suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatrician
Suspected Patient
ASD Dx
ASD Dx
4.5 yrs old
2 yrs old
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Neonatal Diagnosis in Two Days: STAT-Seq
“A lot of people are going to realize that this
is the future.”
Richard Gibbs, Baylor College of Medicine
50 hours to diagnosis for $13,500
One test – 600 rare diseases
CONFIDENTIAL
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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.
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N-of-One’s Solutions: Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-One® Realizing Precision Medicine
12 yo M: Glioblastoma
• NGS identified BRAFV600E mutation, more commonly
associated with melanoma
• Impact: Oncologist petition for vemurafenib (FDA: melanoma)
25 yo F: Breast Cancer
• arrayCGH detected high-level Her2 gain in recurrent tumor
• Status post mastectomy: disease free
• Impact: N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F: Lung Cancer
• Her2/neu mutation detected by DNA MassARRAY
• Impact: Successful petition by oncologist for off-label use of
Herceptin; patient in remission nearly 2 years
79 yo M: Pancreatic
• High-level c-Met expression detected
• Impact: N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved: thyroid cancer)
N-of-One material confidential. Do not distribute
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Buckeye
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PartnersThank You BioForward Vision Team and…
Dr. David Rimm - Yale
Dr. Laura Macconaill – Dana Farber
Dr. Dan Haber, Dr. Long Le, Dr. Mehmet Toner – MGH
Dr. Jay Flatly – Illumina
Dr. Kevin Knopp, Dr. Chris Petty – 908 Devices
Dr. Stan Lapedis - SynapDx
Dr. Andrew Barry, Dr. Nate Cosper, Dr. Mark Roskey
Dr. Cliff Hoyt, Dr. Brad Rice, Dr. Josh Moho – PKI
Dr. Irene Rombel – Biotech Analyst
Google Ventures, NorthBridge Partners, General
Catalyst, Arch Ventures
Buckeye Growth Partners
Solect Solar
Hinweis der Redaktion
Need to personalize specific theraptutics – lots of money wasted in the older pharma model – recent report described that adverse drug reactions are now the 4th leading cause of death – and in terms of efficacy – some of the best thereputics until recently were only 60% efficacious – some particularly cancer therapeutics much worse
With transition
Figure 1
Start off with an example of a collaboration we have with CMH where LST technologies are impacting some of the non-direct production costs …and this team NGS programs are in fact at the cusp of being a really clinically translational tool.Started working with Stephane Kingsmore 4 or 5 years ago when he was at NCGR – with Darrell Dinwiddie…implementing automation and uF to streamline Sample prep. Couple year ago – move to CMH ..implement some of the approaches they had developed in a clinical setting.Developed an NGS based test for 595 recessive monogenic diseases suing NGS …started to implement if clinically