How to boost R&D for a low-cost, How to boost R&D for a low-cost, point-of-care rapid diagnostic test point-of-care rapid diagnostic test and better drugs for tuberculosisand better drugs for tuberculosis
Meeting with Médecins Sans Frontières Geneva, April 11, 2008
Giorgio RoscignoCEO / FIND
FINDFIND
• VisionVisionTo impact quality of life of people suffering from poverty-related diseases
• MissionMissionTo develop rapid, accurate, easy to use and affordable point of care diagnostic tests to help fight diseases that disproportionally affect the poor
FIND’s Operational modelFIND’s Operational model
• FIND is a not-for-profit (US 501 c3) Swiss Foundation• Co-invests with partners in order to lower risk, reduces
break-even time, and significantly reduces the barrier for a commercial company to invest and moves the technology along the value chain.
• As a not-for-profit, FIND can leverage its investment against the affordability of the product for the FIND-Target Markets in the High Disease Burden countries and low income countriesPublic sector and private not-for-profit sectors
DevelopmentEvaluation
Demonstration
Moving from development to impactMoving from development to impact
Adoption into globalpolicy
Collecting evidence for scaling up
Impact on poor patients
CONTEXTLimited infrastructures
POLITICALRights
InfluenceFreedom
SOCIO-CULTURALStatusDignity
HUMANHealth
EducationNutrition
ECONOMICConsumption
IncomeAssets GENDER
Poverty is multidimensionalPoverty is multidimensional
WHO/OECD, 2001
Tests should ensure equity of access(Patient centered approach)
Tests must be cheap, if not free(Public/private no profit)
Test should work within local conditions(Part of the demonstration phase/knowledge sharing)
Equity and societal cost effectiveness analysis of Equity and societal cost effectiveness analysis of new Dx in Lesothonew Dx in Lesotho
Scope of the study• To synthesise an approach for assessing impact of new Dx
tools and modalities on equity of access to TB diagnosis
Specific objectives
• To develop locally appropriate tools to describe poverty profile and geographic distribution of TB patients
• To assess main barriers to TB diagnosis in Lesotho • To assess health system costs of new TB diagnostics• To assess the cost effectiveness of new tools
Source: The Treatment Action Group (TAG) report on tuberculosis (TB) research and development (R&D) in 2006
Detection of TB still relies on microscopyDetection of TB still relies on microscopy
Only one quarter of TB cases in the world are ever really diagnosed and reported as smear positives
New technologies, especially molecular-based, have promising potential
But spending on TB R&D diagnostics currently represents less than 8% of TB research funding
•Resolution testing (screening negative drug resistance, e.g., culture)
Clinic / Health Postm
icro
sco
py
sym
pto
ms
Peripheral Lab
Fraction of patients seen
Reference LabSurveillance
• Surveillance• Reference methods• Network supervision
Sur
veill
ance
•Screening•Primary care
•Passive case finding
•Detect and treat
5 %
10 %
25 %
60 %cu
ltu
re
Patient-centered approach based on a tiered level Patient-centered approach based on a tiered level laboratorylaboratory
Regional Lab
FIND budget
spending
75 %
Det
ect
ion
Res
olut
ion
25 %
FIND / TB diagnostic pipelineFIND / TB diagnostic pipeline
Health Post
Referral Hospital
Microscopy Center
20122007 2009 2010Health Level
Manual NAAT
LED Microscopes
Liquid Culture
Rapid speciation
Projects 20112008
Rapid Molecular DST
Interferon Gamma Assays
Fully automated NAAT
Evaluation
Demonstration
Eval
Demonstration
STAG Access
STAG
I
I
A I
A
STAG A
Access
DemoFeasibility &Develop
Feasibility &Develop
I
Enose
Demonstration
DemonstrationEvalDevelopFeasibility &
A
A Imp I
Acc I
STAG
STAG
AAcc
AB detection
AG detection
Feasibility & Development
Feasibility & Development
Feasibility & Development
STAG
STAG
STAGDemonstration
Demonstration
Demonstration
DemonstrationEvaluation
Evaluation
Evaluation
Eval
STAG
Access
Impact
Impact
Impact
Access
Acc
Imp
Imp
Access
Access
Access
A
Impact
A
STAG
Gaps in R&D (1)Gaps in R&D (1)The slow road to microscopy diagnosis of TBThe slow road to microscopy diagnosis of TB
The starting-point in the fight against all contagious diseases is the obligation to report, because without this most cases of the disease remain unknown. Robert Koch, 1905
A new POC TB Diagnostic tool could save up to 400,000 lives per year. Nature
For Molecular Testing the main driver is to the POCFor Molecular Testing the main driver is to the POC
PRIMARY
SECONDARY
TERTIARY• FROM: centralized big laboratory machines
TO: self-contained simple-to-use chemistry & equipment
Home
Referral
Hospitals
Rural and Regional
Hospitals
Health Centers
or Outpatient
Clinics
Doctor’s
Office
• Two key areas: Biomarkers & Technology
• No well-defined molecular targets (except DNA)
• Dx target identification ongoing– Various “Omics” approaches taken
• Detection technology dependent on type and number of markers employed– LFI most likely technology for POC but limited by sensitivity and
number of analytes
MtbMtb Antibody / Antigen Dx Antibody / Antigen Dx
Gaps in R&D (2)Gaps in R&D (2)TB Biomarker ResearchTB Biomarker Research
Lack of systematic approaches to marker discovery: no consensus on TB biomarkers
Lack of reproducibility of preliminary biomarker results (e.g., antibodies, LAM antigen)
Probable causes of failure and bias:
opportunistic approaches
poor understanding of in vivo antigen processing
lack of appropriate detection technology
inefficient sample preparation procedures
poorly documented clinical samples
• Biomarker discovery:– Academia
• Immunology
• NAAT targets
• Biomarker validation:– Commercial partner
• Extensive clinical trials
• Prototype products
Boosting R&D for a low-cost, Boosting R&D for a low-cost, point-of-care rapid diagnostic testpoint-of-care rapid diagnostic test:
bridging the gaps
• Appropriate technologies with appropriate partners
MtbMtb Antibody / Antigen Dx Discovery Antibody / Antigen Dx DiscoveryPOC by combining biomarkers and technology
• Academic research (UCI) leads to novel, high throughput protein expression technology
• FIND technology scouting identified this outstanding opportunity to close serology target gaps
• UCI spin-off founded ImmPORT Inc., who became a FIND partner
• This PPP generated first ever whole Mtb proteome array chip to identify unknown antibody targets serving as key reagents for POC development
• Partner company attracted by FIND expertise and short term cash rather than long term advanced purchasing mechanism
How to bridge and which incentives for novel How to bridge and which incentives for novel biomarkers and appropriate technologybiomarkers and appropriate technology
Biomarkers High risk / high cost
Academia driven
Industry focused primarily on big markets (e.g., cancer, diabetes,...)
Bioinformatics challenges
Validation and reproducibility are critical issues
Incentives:
Publications, IP, additional R&D funds
Prizes
Research reagents contracts (Ab/Ag)
Small business grants linking academia and companies
Technology Big Dx companies only in profitable
segments (sequencing, arrays)
Biotech / small-med. tech. as major drivers of innovation (short to medium term) but often prohibited by short term goals of VCs (profit) [ImmPORT]
High profile research institutions and military (MIT, DARPA) may provide “out of the box” solutions (medium to long term) but TB dx applications are typically not an “A” priority [Cepheid]
Incentives:
“Public” Venture Capital to support small-med companies
Prizes to establish market value of technological platform
Advanced market commitment (larger company)
IVD Industry operates a IVD Industry operates a differentdifferent business model business model from Pharma industryfrom Pharma industry
Far more sensitive to cash flows; IVD projects take only a few years and product sales cash flows are critical in the short term
1. Technology cycle times are only a few years; the need to get to the break-even point is greater
2. Replacement products from competitors eat into margins and profit far earlier than in Pharma
3. IP is important but linked to shorter product lifetimes; results in limited ROI on IP
Is there a role for novel market incentives in Is there a role for novel market incentives in catalyzing IVD Development Projects?catalyzing IVD Development Projects?
• The « Carrot » of a « Prize »?– Academia: doubtful, since main driver is peer
recognition and publications – money is always welcome
– Public VC for commercial partners: most likely, since it helps project « hurdle rates » and break-even points
– For large companies: doubtful, as it must be sufficiently significant to actually be an « incentive »; i.e. $ in millions
– The Advance Market Commitment: no, not a driver for IVD companies as cash flow is king and most IVD’s are not « commodity-like » possibly attractive to larger DX Co with mature technologies .
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