TB Vaccine Stakeholder Meeting and Luncheon - Aeras€¦ · and ensure global market access ... •...
Transcript of TB Vaccine Stakeholder Meeting and Luncheon - Aeras€¦ · and ensure global market access ... •...
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TB Vaccine Stakeholder Meeting and Luncheon
3 December 2015
Cape Town, South Africa
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Jacqueline E. Shea, PhD
CEO
Overview of Aeras’s Strategy and Progress
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Agenda
• Mission
• Organizational overview and model
• Preclinical development
• Clinical development
• Global pipeline
• Challenges to TB vaccine development
• R&D strategy
• Collaboration
• Portfolio management
• Stakeholders
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Developing new TB
vaccines that are
affordable and
accessible to all who
need them
Our Mission
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• PDP founded in 2003
• Nonprofit biotechnology organization with
in-house capabilities in portfolio
management, preclinical development,
translational product development, policy,
advocacy, resource mobilization and
finance
• Offices
- Rockville, MD, USA (headquarters)
- Cape Town, South Africa
- Beijing, China
• Technical advisory groups incorporating expertise from around the world
• ~ 90 total employees globally
Overview of Aeras
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Aeras Africa
• Founded in 2008
• Approx. 20 staff members and contractors with industry, academic and
CRO experience
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• Real-time support to
collaborating clinical trial sites
• Extensive network of partners
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Aeras Asia
• Aeras Biotech Beijing Limited opened
in 2013
• 2 staff and a contractor
• Several ongoing partnerships and
collaborations
• Landscape analysis of research
environment underway to identify other
partnership opportunities
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Preclinical Development • In-house capabilities include:
– vaccine design
– program management
– research
– assay development
– immunology
– animal studies
• 12,000 sq. ft. of fully equipped
BSL-2 laboratory space
• Extensive experience in antigen
selection, platform development,
lead optimization, process
development, patent and
regulatory filings
• Wide range of animal modeling
and immunology proficiency
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Clinical Development • Network of clinical trial partner sites in North
America, Europe, Africa and Asia
• Over 30 clinical trials with multiple candidates
and partners in the past 12 years
• In-house capabilities include:
- Clinical operations
- Safety
- Epidemiology and site assessment
- Stats and data management
- Medical writing
- Specimen and IP management
- Immunology lab
- Regulatory affairs group
- Diagnostic and mycobacteriology lab capacity at
sites with EQA
• Flexible operating model
– 100% Aeras managed
– Hybrid with CROs and/or collaborators (e.g. pharma
partners, NIH/HVTN)
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Durban, Johannesburg, Klerksdorp,
Pretoria, Rustenburg, Soshanguve,
Soweto, and Tembisa, South Africa
Oxford and Birmingham, UK
Lausanne, Switzerland
St. Louis, MO, US
Lenexa, KS, US
Dakar, Senegal
Sichuan, China Guangxi, China
Bangalore, India
Kampala, Uganda
Svay Rieng, Cambodia
Kericho and Kisumu, Kenya
Lusaka, Zambia
Maputo, Mozambique
Cape Town, Paarl, Tygerburg,
and Worcester, South Africa
Clinical - Completed
Clinical - Current
Epidemiological – Completed
Epidemiological – Current
Stockholm, Sweden
Tampere, Finland
Hanoi, Vietnam
Clinical and Epidemiological Studies
Portland, OR, US
Lebanon, NH, US
Rochester, NY, US
Winston-Salem, NC, US
Henan, China Jiangsu, China
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Phase 1 Phase 2a Phase 2b Phase 3
DAR-901
Dartmouth, Aeras
RUTI
Archivel Farma, S.L
VPM 1002
SII, Max Planck, VPM, TBVI
Vaccae™
Anhui Zhifei Longcom
MTBVAC Biofabri, TBVI, Zaragosa
H1/H56: IC31
SSI, Valneva, Aeras
M72 + AS01E
GSK, Aeras
Ad5 Ag85A
McMaster, CanSino
H4: IC31
Sanofi Pasteur, SSI, Aeras
ChAdOx1.85A / MVA85A
Oxford, Birmingham
ID93 + GLA-SE
IDRI, Wellcome Trust, Aeras
MVA85A / MVA85A (ID, Aerosol)
Oxford
TB / FLU-04L
RIBSP
Global Clinical Pipeline of
TB Vaccine Candidates
Viral Vector
Protein / Adjuvant
Mycobacterial – Whole Cell or Extract
Please note: Information is self-reported by vaccine sponsors.
Revised on Nov 18, 2015
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Phase 1 Phase 2a Phase 2b Phase 3
DAR-901
Dartmouth, Aeras
RUTI
Archivel Farma, S.L
VPM 1002
SII, Max Planck, VPM, TBVI
Vaccae™
Anhui Zhifei Longcom
MTBVAC Biofabri, TBVI, Zaragosa
H1/H56: IC31
SSI, Valneva, Aeras
M72 + AS01E
GSK, Aeras
Ad5 Ag85A
McMaster, CanSino
H4: IC31
Sanofi Pasteur, SSI, Aeras
ChAdOx1.85A / MVA85A
Oxford, Birmingham
ID93 + GLA-SE
IDRI, Wellcome Trust, Aeras
MVA85A / MVA85A (ID, Aerosol)
Oxford
TB / FLU-04L
RIBSP
Global Clinical Pipeline of
TB Vaccine Candidates
Viral Vector
Protein / Adjuvant
Mycobacterial – Whole Cell or Extract
Please note: Information is self-reported by vaccine sponsors.
Revised on Nov 18, 2015
DAR-901
Dartmouth, Aeras
RUTI
Archivel Farma, S.L
VPM 1002
SII, Max Planck, VPM, TBVI
Vaccae™
Anhui Zhifei Longcom
MTBVAC Biofabri, TBVI, Zaragosa
H1/H56: IC31
SSI, Valneva, Aeras
M72 + AS01E
GSK, Aeras
Ad5 Ag85A
McMaster, CanSino
H4: IC31
Sanofi Pasteur, SSI, Aeras
ChAdOx1.85A / MVA85A
Oxford, Birmingham
ID93 + GLA-SE
IDRI, Wellcome Trust, Aeras
MVA85A / MVA85A (ID, Aerosol)
Oxford
TB / FLU-04L
RIBSP
Viral Vector
Protein / Adjuvant
Mycobacterial – Whole Cell or Extract
DAR-901
Dartmouth, Aeras
RUTI
Archivel Farma, S.L
VPM 1002
SII, Max Planck, VPM, TBVI
Vaccae™
Anhui Zhifei Longcom
MTBVAC Biofabri, TBVI, Zaragosa
H1/H56: IC31
SSI, Valneva, Aeras
M72 + AS01E
GSK, Aeras
Ad5 Ag85A
McMaster, CanSino
H4: IC31
Sanofi Pasteur, SSI, Aeras
ChAdOx1.85A / MVA85A
Oxford, Birmingham
ID93 + GLA-SE
IDRI, Wellcome Trust, Aeras
MVA85A / MVA85A (ID, Aerosol)
Oxford
TB / FLU-04L
RIBSP
Viral Vector
Protein / Adjuvant
Mycobacterial – Whole Cell or Extract
DAR-901
Dartmouth, Aeras
RUTI
Archivel Farma, S.L
VPM 1002
SII, Max Planck, VPM, TBVI
Vaccae™
Anhui Zhifei Longcom
MTBVAC Biofabri, TBVI, Zaragosa
H1/H56: IC31
SSI, Valneva, Aeras
M72 + AS01E
GSK, Aeras
Ad5 Ag85A
McMaster, CanSino
H4: IC31
Sanofi Pasteur, SSI, Aeras
ChAdOx1.85A / MVA85A
Oxford, Birmingham
ID93 + GLA-SE
IDRI, Wellcome Trust, Aeras
MVA85A / MVA85A (ID, Aerosol)
Oxford
TB / FLU-04L
RIBSP
Viral Vector
Protein / Adjuvant
Mycobacterial – Whole Cell or Extract
DAR-901
Dartmouth, Aeras
RUTI
Archivel Farma, S.L
VPM 1002
SII, Max Planck, VPM, TBVI
Vaccae™
Anhui Zhifei Longcom
MTBVAC Biofabri, TBVI, Zaragosa
H1/H56: IC31
SSI, Valneva, Aeras
M72 + AS01E
GSK, Aeras
Ad5 Ag85A
McMaster, CanSino
H4: IC31
Sanofi Pasteur, SSI, Aeras
ChAdOx1.85A / MVA85A
Oxford, Birmingham
ID93 + GLA-SE
IDRI, Wellcome Trust, Aeras
MVA85A / MVA85A (ID, Aerosol)
Oxford
TB / FLU-04L
RIBSP
Viral Vector
Protein / Adjuvant
Mycobacterial – Whole Cell or Extract
DAR-901
Dartmouth, Aeras
RUTI
Archivel Farma, S.L
VPM 1002
SII, Max Planck, VPM, TBVI
Vaccae™
Anhui Zhifei Longcom
MTBVAC Biofabri, TBVI, Zaragosa
H1/H56: IC31
SSI, Valneva, Aeras
M72 + AS01E
GSK, Aeras
Ad5 Ag85A
McMaster, CanSino
H4: IC31
Sanofi Pasteur, SSI, Aeras
ChAdOx1.85A / MVA85A
Oxford, Birmingham
ID93 + GLA-SE
IDRI, Wellcome Trust, Aeras
MVA85A / MVA85A (ID, Aerosol)
Oxford
TB / FLU-04L
RIBSP
Viral Vector
Protein / Adjuvant
Mycobacterial – Whole Cell or Extract
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Translating Early Stage Discoveries
into Products
Discovery
Applied
Research
Clinical
Development
Regulatory
Clearance
Aeras Activities, Management, Oversight, Support
Process
Development*
cGMP Clinical
Manufacture* Clinical Trials
Preclinical
Development
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*Provided by a strategic partner
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Key Challenges — Scientific Questions
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What constitutes a
protective immune
response?
Where do we need the
response? (local vs
systemic)
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Key Challenges — Missing Tools
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• Measure of level of exposure to the organism
• True measure of infection
• Measure of burden of Mtb during latency
• Better measure of cure
Enhancing knowledge about TB
• Validated, predictive animal models
• An in vitro functional assay of vaccine effect
• A correlate of vaccine-induced protection
• A human challenge model
Improving candidate selection
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Aeras’s Primary R&D Strategic Goal
Ultimate goal is to develop, register
and ensure global market access
to a universal vaccine for all age
groups and populations
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- Initial focus on a vaccine to
prevent TB disease in
adolescents and adults as
primary transmitters of disease
- Accessibility of new vaccines
must be considered alongside
product development
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An Adolescent/Adult TB Vaccine Could Have
a Greater Impact on TB in Children 0-4 Years
Old than an Infant TB Vaccine
*Adult vaccine given every 10 years
17 White, R., Harris, R. “Potential public health impact of new TB vaccines: Prevention of disease,
infection and immunotherapy “. 4th Global Forum on TB Vaccines. Shanghai, China. 25 April
2015. Conference Presentation
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Strategic Imperatives
1. Move the most promising candidates through to successful
registration and global access
2. Use translational and experimental medicine studies to de-risk
candidates at an earlier and less costly stage of development
3. Develop new and improved human challenge and animal models of
disease and leverage research findings to inform correlates of
protection and accelerate product development
4. Diversify the pipeline through innovation and select the best
candidates in each class for further development
5. Expand and diversify the funding base to support TB vaccine
development
6. Strengthen our partnerships and organization to enable TB vaccine
development
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• Translational and
mycobacterial expertise
• Strong networks and
partnerships
• Flexible collaboration model
• Convener & coordinator
• Advocacy & resource
mobilization
Collaboration is Essential
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Portfolio Management Approach
Active management
of projects and programs
Advance the most promising
candidates
Framework of harmonized criteria
Annual review process
Portfolio Management
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Recent Major Funders and R&D Partners
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And special thanks to the sites and participants
in our clinical trials!
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Preclinical Development of TB Vaccines
Barry Walker, PhD
Vice President, Preclinical Development
Where we are now, where we need to be and how we will get there
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Preclinical: The Toolbox
• The science
• Strategic vision
• Preclinical investigations, studies, experiments
– animal studies and immunology
• Collaboration and engagement
• Portfolio management
• Novel approaches – human challenge
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Gaps in Pipeline Diversity
Portfolio Gaps
• CD4
– Other helper types
• Antibodies
– Specific pathways
• Inducing specific T cell
functionality
• Anatomical and
functional localization
• Novel Immune
regulation
• Quality vs Quantity –
Antigen selection
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Preclinical Strategy
• Develop new and improved human challenge and animal models of disease
• Leverage research findings to inform correlates of protection and accelerate product development
• Diversify the pipeline through innovation and select the best candidates in each class for further development
• Select protective antigens
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Model Development:
Sharpening the Tools
• NHP
– Lowering of challenge dose
– Enhanced diagnostics (i.e. PET/CT)
• Guinea Pig
– Continued refinement/harmonization of the platform
– Natural infection model
• Mouse
– Kitchen sink experiment – can we extend the dynamic range of the model?
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• Robustness and reproducibility of all animal models is a key issue
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Flexible Partnering Model
Accelerator
BCG Aerosol
Direct Investment
In Projects
Collaboration and
Engagement Active Management
with Partners
Improving the
tools, reagents
Viral Vectored
Strategies
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Landscaping,
Thought
Leadership
New
Approaches
New
Vaccinology
The CTVD
Partnership
Novel
Immunology
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Human Challenge Model • Benefits of a human challenge model
– Assess preliminary vaccine efficacy prior to
entering classical clinical trials
– Could help identify new vaccine candidates capable
of inducing protective immunity
• Using infectious, but ultimately controllable
(safe), and detectable strains of Mtb
• Human challenge model must reflect a
relevant vaccine effect
• Primary focus is on pulmonary delivery as
the natural portal of entry, although
intradermal delivery is also being explored
• This program is funded through Aeras and
the Bill & Melinda Gates Foundation, with a
consortium of partners in the US and the UK
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Summary
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Diversity
Partnerships & Collaboration
Translational Development
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Update on Clinical Development and
Aeras’s Programs in Africa
Dereck Tait, MBChB, FRCPath
Clinical Director, Aeras Africa
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Africa is a Key Region for
TB Vaccine R&D
• High incidence of TB
• Strong biomedical
research infrastructure
• Extensive experience in
TB vaccine development
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Aeras’s Clinical Development Strategy
Goal: Accelerate and streamline clinical development of TB vaccines
Novel trial designs
Experimental medicine
Discovery and validation of correlates of
protection and/or risk
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Experimental Medicine and
Novel Trial Designs
PHASE 3
PHASE 3
Prevention
of Infection
Prevention of
Recurrence
PHASE 1
PHASE 1
PHASE 2a
PHASE 2a PHASE 2b
PHASE 2b +/or
De-risking candidates at lower cost and earlier stages of
development
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Clinical Studies in Africa
• Phase 1 safety and immunogenicity studies
• Intensive immunology study
• Dose ranging
• Prevention of infection
• Prevention of disease
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Current Clinical Development Activities in
Collaboration with Partners in Africa
• 8 ongoing studies
• Phase 1 through Phase 2b
• ~5 000 participants
• 15 sites in three African countries
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Month 6
QFT (-)
QF
T (+
)
Repeat QFT at 9
and 12 months
Screening
/enrollment
QFT (-)
Month 3
(Day 84)
QFT (-)
QF
T (+
)
Safety visit at Month
6 (BCG Group) or
Month 8 (AERAS-
404 or placebo
groups)
Month 12
QFT (-)
QF
T (+
)
Repeat QFT at 15
and 18 months
Month 18
QFT (-) Q
FT (+
)
Repeat QFT at 21
and 24 months
Month 24
QF
T (+
)
Repeat QFT at 27
and 30 months
If QFT (-), follow
up is complete
1st Prevention of Infection Trial of a New TB
Vaccine Underway in Adolescents
• H4; BCG; placebo – 1:1:1
• Primary Mtb infection endpoint - QFT conversion from a negative to positive test
at any time-point after Day 84
• Initial results expected 3Q2016
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• 3506 participants. Sub-Saharan Africa
• Healthy, IGRA+ and HIV negative adults (18-50 years old)
• Stable, controlled chronic non-TB disease allowed
50% randomized to Placebo
(double blind)
50% randomized to
M72 AS01E
21 TB Endpoints
36 months follow-up
TB-018, Proof-of-Concept Phase 2B
Success criterion = log-rank p-value < 0.1 for definite Pulmonary TB (HIV-)
Two intramuscular doses of vaccine or placebo
One month apart
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M72 Efficacy Study Biobank
• 90% of TB-018 participants enrolled in
biobank study
• Objectives
– Primary - to collect samples to evaluate potential biological markers correlated to the risk for TB
– Secondary - to evaluate immune correlates of protection from TB in participants vaccinated with M72/AS01E
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H4, H56 & BCG Phase 1 Immune Correlates
in Adolescents
• Collaboration with Sanofi
Pasteur, SSI, DAIDS, HVTN
• Rationale – To generate
immunological data on a wide
range of immune responses to
increase the likelihood of detecting
responses correlating with risk or
protection in the prevention of
infection Phase 2 studies.
• Recruitment on-going
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Ongoing Phase 1 and 2 Studies
• H4:IC31
– Collaboration with Sanofi Pasteur
– Infant dose escalation study
– 229 participants; 1 cohort still to enroll
• H56:IC31
– Collaboration with SSI
– Adult dose finding; Dose selected for further study
– Safety and immunogenicity study in patients recently treated for TB
– Fully recruited; Follow-up ongoing
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H56:IC31 Phase 2 Prevention of Infection in
Adolescents (in planning)
• Collaboration with SSI, University of Bergen,
SATVI, AURUM and Mwanza
• Study design to mimic H4 POI study
• Projected start 2Q2016
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Community Engagement in
Clinical Research
• Establish or augment CABs
for support of TB vaccine
trials
• TB, vaccine, and research
literacy training
• Establishment of a Regional
Africa TB Vaccine CAB
• Currently mapping and evaluating Community
Advisory Boards (CABs) at all clinical trial sites
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Clinical Development: Looking Ahead
• Implementing novel clinical trial designs to
accelerate clinical development
• First results from new efficacy studies
• New preclinical candidates to diversify global
pipeline
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Current Clinical Sites
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Building Global Support for TB and TB
Vaccine R&D
Dara Erck
Vice President, External Affairs
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TB R&D Funding Gap
• The estimated annual funding gap for TB R&D of US$1.3 billion1,2
• Full response to TB epidemic costs US$8 billion per year1
46 Sources: 1WHO TB Surveillance Report, 2015; 2TAG, Stop TB Partnership 2015 Report on TB Research Funding Trends
3G-FINDER Public Search Tools
21% 25% 20% 16% 19% 20% 19%
$456 M
$497 M
$613 M $636 M
$584 M $562 M
$580 M
0
100
200
300
400
500
600
700
2007 2008 2009 2010 2011 2012 2013
US
$ in
Millio
ns
Funding for TB R&D3
Other TB R&D
Vaccines
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Resource Mobilization
47 Source: G-FINDER Public Search Tools (2013 Data)
• TB R&D and TB vaccine
R&D funding is dominated
by a small number of
donors
• Funding the ambitious
research agenda necessary
to support the WHO End TB
Strategy, The Global Plan to
Stop TB, and organizations
like Aeras, will require more
robust funding by more
donors
Bill & Melinda Gates
Foundation (33%)
Aggregate
Pharmaceutical and
Biotechnology
Companies (24%)
NIH (16%)
Funders Contributing
<2%
(9%)
DFID (5%)
DGIS (4%)
EDCTP (4%)
SSI (3%) UK MRC (2%)
TB Vaccines: $108.4 M
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Advocating for TB R&D
48 Source: WHO Global TB Report 2015
Tuberculosis kills more people than any
other single infectious disease agent
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The Cost of Inaction
• By 2030, a five-year delay in investing in new tools could result in a tremendous human and economic toll:
49 Source: Global Plan to End TB 2016-2020
8.4 million additional TB cases
US $181 billion in lost productivity
1.4 million additional TB deaths
US $5.3 billion in additional costs for TB
treatment
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Thank You. To Contact Us:
Global Headquarters
Dara Erck, VP External Affairs
Aeras Asia
Sharon Chan, Head of Asia Office
Aeras Africa
Dereck Tait, Clinical Director