Developing New Vaccines to Address the TB Pandemic

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Developing New Vaccinesto Address the TB Pandemic

• Jerald C. Sadoff, MD
• Aeras Global TB Vaccine Foundation
• Stop TB Partners Forum
• March 24, 2009
• Rio de Janeiro, Brazil

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Barriers to Research Development of New Tools

• Scientific uncertainty
• Market uncertainty
• Too much risk relative to perceived gain for
  private sector
• Lack of clinical trial and manufacturing capacity

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Addressing Barriers through Product Development
Partnerships (PDPs)

• Non-profit enterprises created to accelerate RD
  for new products to fight AIDS, TB, malaria and
  other neglected diseases
• Manage resources and partnerships from across
  public, private and philanthropic sectors
• Complements partners expertise, facilities and
  capacity
• Utilize a portfolio management approach
• Act as a catalyst to advance new products through
  the development pipeline towards registration and
  launch
• Range from virtual to bricks and mortar
  depending on availability of external capacity
• Commitment to access, availability and
  affordability

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Invention of BCG Vaccine
By Calmette Guérin 1908-1921 No new TB
Vaccine in almost 90 years
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BCG Ineffective Against TB Pandemic

• Unreliable protection against pulmonary TB, which
  accounts for most TB worldwide
• Despite wide use, BCG has had no apparent impact
  on the growing global TB epidemic
• Not known to protect against latent TB
• Not recommended for use in infants infected with
  HIV
• Does reduce risk of severe pediatric TB disease

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Potential of a New TB Vaccine

• Eliminate TB as a global public health threat, in
  line with global targets (lt1 case/million)
• In conjunction with new drugs and diagnostics
• Vaccines can prevent onset and reduce
  transmission of disease
• TB will not be eliminated without a new TB
  vaccine
• Safe and effective in preventing TB in children,
  adolescents and adults, including people with HIV
• Protect against all forms of TB including MDR
  and XDR
• Reduce the cost and burden of TB related medical
  care on health care systems and patients

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Aeras Global TB Vaccine Foundation

• Mission
• To develop new, more effective TB vaccines and
  ensure their affordability and availability to
  all who need them.
• Goals
• A more effective, safe and affordable TB vaccine
• Identify correlates and surrogate markers of
  vaccine induced protection
• Develop second generation TB vaccines with
  increased potency and broader protection

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Aeras Global Vaccine Development Partners
Foundations/ Governments/ NGOs Bill Melinda
Gates Foundation, U.S. Ministry of Foreign
Affairs of Denmark The Netherlands Ministry of
Foreign Affairs, the Netherlands Centers for
Disease Control and Prevention (CDC),
U.S. Fogarty International Center and NIAID,
National Institutes of Health, U.S. Research
Council of Norway, Norway 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 Manhiça Health Research Centre,
Mozambique Medicine in Need (MEND), U.S. Stop TB
Partnership, Switzerland TB-Alert, United
Kingdom Tuberculosis Vaccine Initiative (TBVI),
Europe Wellcome Trust, United Kingdom
Academia Oxford 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. Biomedical Primate Research
Center, the Netherlands Case Western Reserve
University, U.S. Central Institute for
Tuberculosis, Russia 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, Germany McGill
University, Canada National Cancer Institute
(NKI), the Netherlands New York University,
U.S. Oregon Health Sciences University, U.S.
Public Health Research Institute, U.S. Stanford
University, U.S. Saint Louis University.,
U.S. University of Bergen, Norway University of
California-Davis, U.S. University of
California-San Francisco, 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
Foundations/Government/NGOs
Academia
Industry
Industry GlaxoSmithKline Biologicals,
Belgium Crucell, the Netherlands Statens Serum
Institute, Denmark ImmunoBiology, United
Kingdom Wuhan Institute of Biological Products,
China Serum Institute, India Thymed,
Germany Alphalyse, Denmark Japan BCG Laboratory,
Japan Korean Institute of TB, Korea Cyncron,
Denmark Cellestis, Australia Immune Solutions,
New Zealand Larimer, U.S. Sanofi Pasteur,
France Smittskyddsinstitutet, Sweden BIOCON,
U.S. Emergent BioSolutions, U.S. Intercell,
Austria Spring Valley Laboratories, U.S.
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Induction of Immunity Prime Boost Infants
BCG or rBCG
IM or as an aerosol
Capsids in bacteria or as an aerosol
24 Weeks
14 Weeks
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TB Vaccine Pipeline
Pre-clinical
Phase II
Phase IIB
Phase I
Phase III
AERAS427
VPM 1002
M. vaccae
Other rBCG rMtb
Recombinant BCGs for priming infants
AERAS 402/ Crucell (2009)
Replication-deficient viral vectored vaccines for
boosting infants, young adults HIV positive
AERAS405 Capsid
AERASOther Virus
MVA85A/ AERAS 485 (2009)
GSK M72
HyVac4/ AERAS 404
Other Protein PSS
Recombinant fusion proteins for boosting infants,
adolescents, young adults, HIV positive
Hybrid 1 SSI
AERASPSS
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BCG immunized Adults St Louis
PRELIMINARY DATA 10 DEC 2008
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Aeras Partnerships in Clinical Development
Cambodian Health Committee Cambodia
St Johns Research Institute India
KEMRI/CDC Kenya
Manhiça Health Research Center Mozambique
Makerere University Uganda
SATVI/University of Cape Town South Africa
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Field Site Development

• Large-scale community-based epidemiologic cohort
  studies and clinical trials are conducted in
  areas with high burdens of TB
• Sites developed in partnership with local
  research institutions
• Build local infrastructure and health
  care/research capacity to perform future Good
  Clinical Practice (GCP) compliant Phase III
  clinical trials
• Professional Development Program builds human
  capacity and contributes to development of local
  clinical research professionals

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Example of Site DevelopmentSouth Africa

• Partnership with South African Tuberculosis
  Vaccine Initiative (SATVI)
• Field site developed in Worcester (120 km from
  Cape Town)
• Infrastructure developed
• State-of-the-art immunology laboratory
• Highly skilled staff capable of performing the
  duties necessary to maintain the infrastructure
  and execute clinical research
• Clinical and office facilities
• Professional Development Program (Siyantinga-
  Reach for the Stars) program initiated in
  2001
• Resource Center established in 2005

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Accomplishments in South Africa

• BCG randomized clinical trial from 2001-2006
  11, 680 infants vaccinated and followed-up for
  two years
• Epidemiology studies involving more than 11,500
  participants
• 4,786 infants
• 6,363 adolescents
• 364 adults
• Conducting Phase I and Phase II studies of 4
  vaccine candidates, several additional trials
  planned for 2009
• Initiating Phase IIb trial of a new TB vaccine
• 231 staff trained since 2004
• Establishment of a locally maintained Quality
  Management System
• Establishment of a locally maintained robust data
  capture mechanism
• Most advanced site for large-scale TB vaccine
  trials in the world

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• A vaccine that sits on
• the shelf is useless
• Dr. Albert Sabin

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Access and Availability

• Future access considered at every stage of
  vaccine development
• Manufacturing
• Guarantee by partners for sufficient production
  and affordable prices, 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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Summary

• A new TB vaccine
• will help achieve public health and global
  development goals
• is critical to controlling TB pandemic
• Aeras and its partners leading effort to develop
  new TB vaccines
• Development process for leading candidates
  identified
• Field sites and manufacturing being prepared in
  partnership with research institutions in endemic
  countries
• Working with researchers on exciting new concepts
  in TB vaccine development
• According to the Global Plan to Stop TB, 1
  billion over the next 10 years is needed to
  develop new TB vaccines

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Aeras gratefully acknowledges the support of the
following major donors
Netherlands Ministry of Foreign Affairs
CENTERS FOR DISEASE CONTROL AND PREVENTION Under
cooperative agreement U10PS000060
Ministry of Foreign Affairs of Denmark