O i i d Ch llOpportunities and Challenges for Scientific Ingenuity in g y

Health Care

Dr R.E.W. (Bob) Hancock, Centre for Microbial Diseases and Immunity ResearchCentre for Microbial Diseases and Immunity Research

University of British Columbia,

Why Innovation?Because Health is a moving targetBecause Health is a moving target

• Aging population• Disease does not recognize borders• Fixing one problem reveals othersg p• Wellness vs. Cure.

Preventative medicine is more cost effectivePreventative medicine is more cost effective.• Population-based vs. personalized medicines

H lth i i b i i i l i t t• Health economics is becoming increasingly important in richer nationsT d t t d lif t l d t b• Tendency to move towards lifestyle drugs may not be sustainable

Health is a moving target - Age

• Life expectancy is increasing• Location Location Location• Location, Location, Location• Age is a major factor in Health

Health is a moving target - Antibiotics• Microbial resistance

( tibi ti / ti i l)(antibiotic/antiviral)• Dry pipeline• Emerging problems,Emerging problems,

Bioterrorism• Void in public policy

Ch i D hi• Changing Demographics (aging, travel, climate, immuno-compromised i di id l i l )

12

16

Dev

elop

ed

individuals, animals)

0

4

8

Tot

al N

umbe

r D

Total # NewAntibacterialAgents (5 yearintervals)

01983-1987

1988-1992

1993-1997

1998-2002

2003

From IDSA “Bad Bugs No Drugs”

Health is a moving targetB d id di tiBedside diagnostics

Hydrogels etc can screen f illi f diff tfor millions of different biomolecules (DNA, proteins, etc.) in a single sample make possible the development ofpossible the development of low-cost clinical bedside diagnostics.

Remote monitoringMicrofluidics

Health is a moving target – CancerSurvival improving but early diagnosis, cancer type and Drug resistance are issues

1950 - 2007

Health is a moving target – Drug Reactions

Rates by sex

Rates by Age

Technology Advances that will drive H lth I tiHealth Innovation

Personalized medicinePersonalized medicine

But is it sustainable?

Principles of PharmacogenomicsGenetic Predisposition

Technology Advances Health Innovation

NodeNode

InteractionInteraction

i / f i iSubset of the Interactions involved in Innate Immunity

(Innate DB)

Innate Immunity/Inflammation is complex Considerable complexity - Multiple receptors, signal

transduction pathways, positive and negative regulators; h d d f t i i d d d(Innate DB)

Drawn using the Cerebral plug-in of Cytoscape: Barsky, Gardy

and Hancock

hundreds of proteins induced or suppressed. InnateDB/Cerebral provides framework for

understanding immunomodulator therapeutics (IDRs)

Technology Advances that will drive Health InnovationHealth Innovation

"Right now, day in and day out, we can perform 400,000 reads of 250 bases each with an accuracy of 99 % b " i h l h l & 4 4 if99.5% or better," Michael Egholm, VP R&D, 454 Life Sciences

Th SOLiDThe SOLiD system achieves 4 gigabases of sequence per

Gigabase sequencing

sequence per run

Technology Advances that will drive Health InnovationHealth Innovation

High throughput sequencing makes sequencing of individual patientsequencing of individual patient genomes possible - 1000 genomes project announced Jan 23, 2008project announced Jan 23, 2008

Can rapidly assess single nucleotide polymorphism (SNP) variationpolymorphism (SNP) variation within patient genomes

SNPs are mutations. Combinations SNPs are mutations. Combinations of SNPs determine health or disease, drug reactions, metabolic rate, susceptibility to infection, heart disease, cancer, etc

Technology Advances that will drive Health Innovation – Lab on a chipHealth Innovation Lab on a chip

This lab-on-a-chip is a miniaturized, portable version

Siemens molecular diagnostics system

Protein Purification

atu ed, po tab e ve s oof a blood-count machine

Three primary components of Sandia's Chemlab

Microfluidics

system fit inside a snow-pea pod. The components (from left to right) include a surface wave acoustic sensor array, a preconcentrator to absorb or adsorb chemical vapors, and a gas-chromatograph column.

Barriers to InnovationBarriers to InnovationTimelines are long; Costs are very high Timelines are long; Costs are very high g; y gg; y g

I d Di (3 11 )

Number of Drugsin each phase

Academic Academic Discovery Discovery (3(3 10 yrs)10 yrs) Industry Discovery (3-11 yr)

Preclinical (1 yr)

in each phase10,00010 15

(3(3--10 yrs)10 yrs)

Preclinical (1 yr)

Phase I (1 yr)

10-156

Phase II (1 yr)

Phase III (3-4 yr)

4

1

The Drug The Drug Discovery Discovery

ProcessProcess

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15YEARS

( y )

Govt Review (2-4 yr)

1ProcessProcess

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 YEARS

Cost ~ $800 million per drug

Barriers to InnovationBarriers to InnovationThe Development GapThe Development GapThe Development GapThe Development Gap

DiscoveryViable

OpportunityDEVELOPMENT GAP Opportunity

Issues Issues Risk

Previous approach was

Capability Funding

to spin off a company

This is the next frontier: This is the next frontier: Our approach Our approach -- Centre for Drug Research & DevelopmentCentre for Drug Research & Development

Barriers to Innovation Barriers to Innovation Approach of CDRD to the Drug Development GapApproach of CDRD to the Drug Development GapApproach of CDRD to the Drug Development Gap Approach of CDRD to the Drug Development Gap

Clinical TrialsPre

Research IntensiveResearch Intensive

Division of Drug Target Identification

LeadDiscovery

TargetConcept

ValidatedTarget

HitDiscovery

OptimizedLeads

Clinical TrialsCost: $200-800M5-8 years

Pre-Clinical$2M

Division of Drug Screening

Division of Drug Target Identification

Division of Drug Design & Synthesis

Division of Drug Delivery

“ Drug discovery in the academic

ValueValue

Division of Drug Evaluation“... Drug discovery in the academic setting is urgently needed to explore alternative paradigms in the currently very inefficient drug

$50-100 K $200 K $50-70 M$8 M

ValueValue discovery process.” AS Verkman

Canadian Government approach to Health Canadian Government approach to Health Inno ation ResearchInno ation Research

GovernmentGovernment

Innovation ResearchInnovation Research

TaxTax Revenue

EconomyEconomy Investment$$$$

Training,Products,

$$$$

UniversityUniversityProducts,Expertise

NCE G C d CFI CRC CIHR NSERCNCEs, Genome Canada, CFI, CRCs, CIHR, NSERC,were all created or expanded to address these issues

A Concerning TrendC di B d t J 2009Canadian Budget Jan 2009

• No new funding for Genome Canada cf. $120M last gyear

• The granting councils (CIHR, NSERC, SSHRC) will see budget cuts of $147 9-million over three yearssee budget cuts of $147.9-million over three years.

• “Strategic reviews” at Health Canada and the Public Health Agency of Canada will result in cuts of $167.8-

illi th i l di $6 3 illimillion over three years, including $6.3-million through “refocusing research to take advantage of advancements in science”.

• New money for infrastructure and scholarships• In the USA almost $16 billion of Obama Stimulus

package appropriated for R&D; $9 9 billion towardpackage appropriated for R&D; $9.9 billion toward the conduct of R&D (mainly basic research)

Opportunities and Challenges for Scientific Ingenuity in Health CareScientific Ingenuity in Health Care

• Health issues change over time and demand i i d/ di l hinnovative and/or new medical approaches

• Technology Advances have the potential, if appropriately applied, to revolutionize Health pp p y pp ,Care

• The timeline for development of new medicines are very long and the process costlymedicines are very long and the process costly

• Canada has installed many innovative mechanisms for stimulating scientific ingenuity to improve our economy (and healthingenuity to improve our economy (and health care)

• The most recent budget is concerning in this dregard.