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AERAS GLOBAL TB VACCINE FOUNDATION
By Calmette & Gurin
1908-1921
No new TB vaccine inalmost 90 years
Invention of Bacille Calmette-Gurin (BCG) Vaccine
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AERAS GLOBAL TB VACCINE FOUNDATION
BCG Vaccine Efficacy BCG is one of the most widely used
vaccines in the world, yet TB remains the
second leading cause of infectious diseasedeaths
Prevents some severe forms of TB inchildren, saves 40,000 to 70,000 children a
year Fails to prevent pulmonary tuberculosis,
the most common form, and TB in adults(nearly two million people die each year)
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AERAS GLOBAL TB VACCINE FOUNDATION
Tuberculosis: TB Vaccine TooDangerous for Babies With AIDS
Virus, Study SaysJuly 2, 2009 The vaccine against tuberculosis that
is routinely given to 75 percent of the worlds
infants is too risky to give to those born infectedwith the AIDS virus, says a new study publishedby the World Health Organization. Itrecommended that vaccination be delayed untilbabies can be tested.
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AERAS GLOBAL TB VACCINE FOUNDATION
WHO Guidance on BCG World Health Organization (WHO)
changed guidelines in 2007
BCG is not recommended for infantsknown to be infected with HIV, due toincreased risk of disseminated BCG
disease (one percent of infants with HIVwho receive the vaccine get disseminatedBCG, 75 percent die)
Difficult to implement in practice
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AERAS GLOBAL TB VACCINE FOUNDATION
Potential of a New TB Vaccine Eliminate TB as a public health
threat, in line with global targets(
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AERAS GLOBAL TB VACCINE FOUNDATION
Block InitialInfection
Prevent Early
Disease
Prevent LatentInfection
PreventReactivation
Disease
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AERAS GLOBAL TB VACCINE FOUNDATION
TB (all types) Incidence
0
400
800
1200
1600
2000
2010 2015 2020 2025 2030 2035 2040 2045 2050
Year
Incidencepermillion
Neonatal pre-exposure
Neonate pre-exposure + add effects
Post-exposure
Mass pre-exposure
Mass pre-exposure + post-exposure
Abu-Raddad,Sabatelli,Achterberg,Sugimoto, Longini,Dye and Halloran
All age groups
*Pre-exposure vaccine with additional effects that reduce the lifetime risk of developing disease in slow progressors byhalf to
about 2.5% and the infectiousness of the smear-positive and smear-negative cases byhalf.
*
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AERAS GLOBAL TB VACCINE FOUNDATION
Aeras Global TB Vaccine FoundationMission
To develop new, more effectiveTB vaccines and ensure theiravailability to all who need them
Goals A more effective, safe and
affordable TB vaccine by 2016 Identify correlates and
surrogate markers of vaccineinduced protection
Develop second generation TBvaccines with increasedpotency and broader protection
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AERAS GLOBAL TB VACCINE FOUNDATION
IndustryGlaxoSmithKline Biologicals, Belgium
Crucell, the Netherlands
Statens Serum Institute, Denmark
ImmunoBiology, United Kingdom
Wuhan Institute of Biological Products, China
Serum Institute, India
Thymed, Germany
Japan BCG Laboratory, Japan
Korean Institute of TB, Korea
Cyncron, Denmark
Immune Solutions, New Zealand
Sanofi Pasteur, France
Smittskyddsinstitutet, Sweden
Emergent BioSolutions, U.S.
Intercell, Austria
Foundations/Governments/
NGOsBill & Melinda Gates Foundation, U.S.
Ministry of Foreign Affairs of Denmark
The Netherlands Ministry of Foreign Affairs,
the Netherlands
Fogarty International Center and NIAID,
National Institutes of Health, U.S.
Research Council of Norway, Norway
Maryland Department of Business and
Economic Development, U.S.
AIDS Fondet, Denmark
Cambodian Health Committee, Cambodia
European and Developing Countries Clinical
Trials Partnership (EDCTP), European
Commission
LHL/ The Norwegian Association of Heart and
Lung Patients, Norway
Planeta Salud, Spain
Mary Lynn Richardson Fund, U.S.
Manhia Health Research Centre,
Mozambique
Medicine in Need (MEND), U.S.
Stop TB Partnership, Switzerland
TB-Alert, United Kingdom
Wellcome Trust, United Kingdom
AcademiaOxford University, United Kingdom
South African TB Vaccine Initiative (SATVI), South Africa
St. Johns Research Institute, India
Makerere University, Uganda
Kenya Medical Research Institute, Kenya
Karolinska Institute, Sweden
Wuhan University, China
Albert Einstein College of Medicine, U.S.
Arizona State University, U.S.
Aurum Institute, South Africa
Biomedical Primate Research Center, the Netherlands
Case Western Reserve University, U.S.Centre for International Health, University of Bergen, Norway
Colorado State University, U.S.
Emory University, U.S.
Food and Drug Administration, U.S.
Foundation for Innovative New Diagnostics (FIND), Switzerland
Harvard University, U.S.
International AIDS Vaccine Initiative (IAVI), U.S.
Johns Hopkins University, U.S.
KNCV Tuberculosis Foundation, the Netherlands
Leiden University Medical Center, the Netherlands
Life Science Research Israel (LSRI), Israel
Max Planck Institute for Infection Biology, GermanyNational Cancer Institute (NKI), the Netherlands
Oregon Health Sciences University, U.S.
Stanford University, U.S.
Saint Louis University., U.S.
Tuberculosis Vaccine Initiative (TBVI), Europe
Tulane University, U.S.
University of California-San Francisco, U.S.
University of California-Los Angeles, U.S.
University of Maryland, College Park, U.S.
University of Tampere, Finland
University of Wales, United Kingdom
Vanderbilt University., U.S.
Walter Reed Army Institute of Research, U.S.
Aeras Global Vaccine Development Partners
Aeras
Foundations/
Government/
NGOs
Industry
Academia
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AERAS GLOBAL TB VACCINE FOUNDATION
TB Vaccine Pipeline
Additional research at the discovery/early pre-clinical level: Bhagawan Mahavir Medical Research Center; Cardiff University; EpiVax, Inc.; ImmunoBiology Ltd.; Infectious Disease ResearchInstitute; Institute de Pharamacologie, Puso; Karolinska Institute; Malaysia-Finlay Institute, NIAID; NIH; Osaka University; Shanghai H&G Biotech; Sequella; UCLA; and, Vanderbilt University.
Vaccine Candidate Pre-Clinical Phase I Phase II Phase IIb Phase III
AERAS402/Crucell Ad35Crucell N.V./Aeras
MVA85A/AERAS-485OETC/Aeras
GSK M72GSK Biologicals/Aeras
Hybrid 1 SSI IC-31SSI, TBVI, Intercell
HyVac4/AERAS-404sanofi pasteur/SSI/Intercell/Aeras
VPM 1002MaxPlanck/Vakzine ProjektManagement GmbH/TBVI
AdAg85AMcMasterUniversity
RUTIArchivel Farma, S.I.
Hybrid 1 SSI CAF01SSI
AERAS-rBCGAeras
AERAS-CapsidAeras
Other rBCG rMtbAlbert Einstein S. ofMed., Institute Pasteur, Univ. of Zaragoza, TBVI
AERAS-other virusAeras
Protein/PolysaccharidesInst. Pasteurde Lille/Inserm, Albert Einstein S. ofMed., Aeras, Karolinska Instit.
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AERAS GLOBAL TB VACCINE FOUNDATION
Challenge Models ($1 million per year for 7 yrs)
TB Vaccine Development TimelineField Site Development ($2-4 million per yr, per site for 7 yrs)
2.5 Years 2 Years 4 Years
$160 Million
4 ofAeras 6 TB vaccine candidates are in clinical trials in Africa;
the others are expected to enter trials in 2010
$160 million to conduct a Phase III licensure trial of one candidate
With sufficient resources, a new TB vaccine could be ready by 2016
The Treatment Action Group estimated a $1.5 billion funding gap
for TB research for 2008 alone
1 - 2 Years 1 Year
Vaccin
eDiscovery
Pre-
ClinicalTestin
g
Phase
I
Phase
II
Phase IIb Phase III
Manufacturing ($5 million per yr for 9 yrs)
$2.5 million $4 mill ion $4 million
Licensure
$1.5 million
Costs associated with thedevelopment of allcandidates in Aeras pipeline
Costs related to thedevelopment ofone TBvaccine candidate
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AERAS GLOBAL TB VACCINE FOUNDATION
Safer in HIV infected infants orothers with immune-suppression
BCG or rBCG boosted with anotherTB vaccine is much better than
either vaccine alone Constructed to over-express
antigens from each stage of the TBlife cycle
Prevent infection and reactivationutilizing prime-boost regimens
A new vaccine candidate with all ofthese properties is expected toenter clinical trials in 2010
Recombinant BCG (rBCG) - A Better BCG
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AERAS GLOBAL TB VACCINE FOUNDATION
Aerosol Delivery of New TB Vaccines
Very small particles (2-4 microns)get deep into the lung, whereinfection occurs
Aerosol delivery may provide aneasy, affordable delivery mechanismthat could eliminate the need for
needles and cold chain and providesuperior protection
Spray Drying
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AERAS GLOBAL TB VACCINE FOUNDATION
Example of Site Development: South Africa
Partnership with South African TuberculosisVaccine Initiative (SATVI)
Field site developed in Worcester (~120 km fromCape Town)
Infrastructure developed: State-of-the-art immunology laboratory
Highly skilled staff capable of performing theduties necessary to maintain the infrastructureand execute clinical research
Clinical and office facilities Professional Development Program
(Siyantinga- Reach for the Stars) programinitiated in 2001
Resource Center established in 2005
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AERAS GLOBAL TB VACCINE FOUNDATION
Accomplishments in South Africa
South African Tuberculosis VaccineInitiative - Most advanced site for large-scale TB vaccine trials in the world
BCG randomized clinical trial of 11,680infants
Cohort studies involving more than11,500 infants and adolescents
Conducting Phase I and Phase IIstudies of 4 vaccine candidates, firstPhase IIb preliminary efficacy study of anew TB vaccine in infants in 80 years
231 staff trained since 2004, including162 female staff
Establishment of a Quality ManagementSystem and data capture mechanism
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AERAS GLOBAL TB VACCINE FOUNDATION
Capacity Building Highlights at Other Sites
State-of-the-art immunology andmycobacteriology lab developed inIndia - first of its kind in the area
State-of-the-art lab and caseverification ward opened in Uganda
Quality management and datamanagement infrastructuredeveloped in India and Uganda
Professional DevelopmentPrograms
Phase I trial at Kenya site
Planned multi-country Phase II trials
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AERAS GLOBAL TB VACCINE FOUNDATION
Benefits of Site Development
and Clinical Research Retain local talent and expertise
Raise awareness about TB in the community
Support and enhance local clinical research capacity
Community health and education
Infrastructure remains in the community
Leverage investment in infrastructure to use for clinicaltrials of other diseases
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AERAS GLOBAL TB VACCINE FOUNDATION
Vaccine Efficacy Trials
MVA85A/AERAS-485
First efficacy trial of a newTB vaccine in infants in
more than 80 years 2,800 infants
In collaboration withSATVI, Oxford-EmergentTuberculosis Consortium
and Wellcome Trust
Additional Proof-of-Concept Studies
Planned for 2010
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AERAS GLOBAL TB VACCINE FOUNDATION
Novel Approaches to Manufacturing
Building manufacturing capacity andpartnerships now to:
Reduce the cost and time tomanufacture and deliver vaccines to all
who need themProduce enough bulk doses of vaccineto meet the worlds estimated need
Work with partners in countries suchas India, China, Korea and South Africato produce, fill, finish and distributevaccines at the lowest possible price
Ensure uniformity of quality
Minimize lag time between licensure
and distribution
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AERAS GLOBAL TB VACCINE FOUNDATION
Access and Availability Future access considered at every stage of vaccine
development Manufacturing
Guarantee by partners for sufficient production and affordableprices, or technology transfer
Manufactured by Aeras with partners in developing world Aeras will not consider vaccine candidates that will be costly to
manufacture on a large scale
Pricing Dual pricing for affordable distribution in resource-poor countries
Cost plus purchase from partner Aeras provides at cost
Distribution Developing world governments International organizations (GAVI, UNICEF) Developing world partners
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AERAS GLOBAL TB VACCINE FOUNDATION
Aeras gratefully acknowledges the support of
the following major donors
NetherlandsMinistry of Foreign Affairs
Ministry of Foreign Affairs of Denmark
THE MARY LYNNRICHARDSON
FUND
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AERAS GLOBAL TB VACCINE FOUNDATION
Thank You!
Formore information:
www.aeras.org
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