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 .