Aeras Global TB Vaccine Foundation

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Aeras Global TB Vaccine Foundation

• All Party Parliamentary Group
• on Global TB
• London, UK
• 16 May 2007

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Aeras Global TB Vaccine Foundation

• Mission
• To develop new, more effective TB vaccines and
  ensure their availability to all who need them
• Goal
• A new TB vaccine in 7 10 years
• ModelInternational, non-profit Product
  Development Partnership

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Mycobacterium Tuberculosis
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Tuberculosis Transmission
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Worldwide Distribution of TB
Rates per 100 000, all forms of TB
0 - 24
25 - 49
50 - 99
100 - 299
300 or more
No estimate
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Tuberculosis Pandemic

• In 2005, 1.6 million deaths and 8.8 million new
  cases of TB
• 2 billion people infected with latent TB
• One third of people living with HIV/AIDS are
  co-infected with TB, with the highest burden in
  Sub-Saharan Africa and Southeast Asia.
• TB is the leading cause of death of HIV positive
  people. In fact, TB accelerates progression of
  HIV into AIDS

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Emergence of Antibiotic Resistance

• XDR-TB is resistant to the most common first line
  drugs and at least two classes of second line
  drugs
• XDR TB in KwaZulu-Natal S. Africa identified in
  2006
• 51 of 52 died of XDR-TB within a mean of 20 days
  from diagnosis
• All patients were HIV positive
• TB difficult to diagnose in HIV positives because
  of their poor inflammatory response

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Invention of BCG Vaccine
By Calmette Guérin 1906-1921 No new TB
Vaccine in 86 years
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BCG Ineffective Against TB Pandemic

• Reduces risk of severe pediatric TB disease
• Unreliable protection against adult pulmonary TB,
  which accounts for most TB worldwide
• Despite wide use, BCG has had no apparent impact
  on growing global TB epidemic
• Not known to protect against latent TB

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Potential of a New TB Vaccine

• Achieve global TB control in 15-20 years
• If new vaccine 50-70 better then BCG
• In conjunction with better drugs and diagnostics
• Minimize TB as a global threat by 2050
• lt1 case/million
• TB will not be eliminated without a new vaccine

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Tremendous Need

• Majority of TB vaccine need in developing world
• Typically, new vaccines licensed for the
  industrialized world first developing countries
  10 to 20 years later

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Yet Barriers for Industry

• Scientific uncertainty
• Uncertain return on investment
• Lack of vaccine development capacity
• Opportunity costs low margin TB vaccine vs. high
  margin lifestyle drug?

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New Financing Mechanisms

• PDPs (push)
• Provides resources for translational research
  (lab to clinical trial)
• Performs preclinical technical assessments and
  clinical development of new products
• increases NPVs for low margin markets
• Advance Market Commitments (pull)
• Donors commit to buying vaccine when it is
  developed
• Guarantees ROI for successful product
• 1st AMC for pneumococcal disease (1.5 bn)

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Aeras Role in TB Vaccine Development

• Goals developing vaccines, ensuring access
• At least one new TB vaccine regimen for infants
  and one for adolescents within 7-10 years
• Full availability and access to all who need TB
  vaccines
• Focusing global TB vaccine efforts
• Product Development Partnership (PDP)
• Partners with industry, academia, philanthropy,
  and government to develop vaccines and conduct
  clinical trials
• Develops vaccines in its own lab and
  manufacturing plant

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Relationship with Partners

• Partner receives
• Support for preclinical development
• Epidemiology and field site preparation
• Support for clinical trials
• Aeras receives
• Partner involvement in disease with developing
  country markets
• Product development and production support
• Guarantee of affordable access to developing world

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Aeras Global Vaccine Development Partners
Industry GSK, Belgium Crucell, Netherlands SSI,
Denmark ImmunoBiology, UK Serum Institute,
India Thymed, Germany Mycos, U.S. Alphalyse,
Denmark Japan BCG Lab. Korean Institute of
TB Cyncron, Denmark Wuhan Biologicals, China
Academia Cape Town Univ., S. Africa St. Johns
Natl Academy, India Wuhan Univ., China Univ of
Bergen, Norway Karolinska Institute, Sweden Max
Planck, Germany Leiden Univ., Netherlands McGill
Univ., Canada Leiden Univ, Netherlands Oxford,
UK UCLA, U.S. U.C. Davis, U.S. Stanford Univ.,
U.S. St. Louis Univ., U.S. Vanderbilt Univ.,
U.S. Colorado St. Univ., U.S. Harvard Univ.,
U.S. Case Western Reserve University, US
Academia
Foundations/Governments/NGOs Bill Melinda
Gates Foundation U.S. CDC, NIH, NIAID, CBER,
FDA DANIDA, Denmark DGIS, The Netherlands NRC,
Norway KNCV, Netherlands LHL, Norway TB Alert,
UK EDCTP, Europe TB-VAC, Europe STOP TB, WHO
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Aeras - Partnerships in South Africa and India
St. Johns Medical College, Bangalore
Palamaner Taluk
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Clinical Trials Field Site Development

• Clinical trials conducted in high TB burden
  countries/regions
• Current field sites in South Africa and India
• With EDCTP, developing sites in Kenya and Uganda
• Seeking additional field sites in Asia (China,
  Viet Nam or Indonesia)
• Building local health care/research capacity
• Professional Development Program builds human
  capacity and contributes to development of local
  research profession

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Approach to Induction of Immunity in Infants and
Adolescents Prime Boost Strategy
24 Weeks
14 Weeks
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Prime Boost Strategy

• Demonstrated to be the best method for induction
  of cellular immunity in humans
• Prime with recombinant BCG or BCG at birth and
  boost at 14 weeks and possibly 6 months of age
  with new recombinant protein or viral vectored
  vaccine
• Adolescents who have been given BCG at birth will
  be boosted with either recombinant protein or
  viral vectored vaccine

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Aeras TB Vaccine Development Pipeline
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Immune Responses and Protection

• All candidate vaccines induce enhanced protection
  compared to BCG in animal models
• All candidate vaccines induce cellular immune
  responses in humans or non-human- primates

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Manufacturing rBCG

• Production of gt200 million doses/yr of bulk
  vaccine for shipment to India other partners
  for drying
• Provides amount and prices required for
  developing world

Aeras manufacturing plant- Fermentation Tanks
Rockville MD
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The introduction of new, effective TB vaccines
will be an essential component of any strategy to
eliminate TB by 2050...New TB vaccines to prevent
childhood and adult forms of TB, to reduce TB in
people coinfected with HIV, and to shorten drug
treatment regimens will fundamentally alter our
approach to TB control.
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UKs Commitment to Global Health

• Key donor to Global Fund to Fight Aids, TB and
  Malaria and Stop TB Partnership
• Global leader in recognition and support of PDPs
  for neglected diseases
• DFID serving as chair of PDP Funders Group
• Supporting AMC for pneumococcal vaccines
• Committed to reaching UN goal of .7 of national
  income dedicated to foreign aid by 2013

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TB Vaccine Development Funding Needs 2006-15
Total 3.641 billion
Global Plan to Stop TB, 2006-15
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TB Vaccine Funding Needs

• 1.5 billion funding gap (2.1 billion expected
  to be available)
• Funding need greatest for discovery,
  translational research, clinical trials and
  manufacturing scale-up

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Aeras TB Vaccine Development Needs

• Advancing development of multiple lead and
  back-up vaccine candidates
• Building capacity and supporting research in
  developing countries
• Vaccine manufacturing and scale-up
• Ensuring access for developing countries

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Summary

• A new TB vaccine
• will help achieve global development goals
• is critical to controlling TB pandemic
• is achievable in 7-10 years
• Aeras and its partners leading effort to develop
  new TB vaccines
• 1.5 billion over the next 10 years is needed to
  achieve this goal