IAVI AIDS Vaccine 2006 Template

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AIDS Vaccines Advancing Development through
Innovation
Frans van den Boom Vice President IAVI European
Programmes 24 October 2007 Helsinki, Finland
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Understanding global inequalities
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• Private health spending

• Malaria cases

Dorling D (2007) Worldmapper The Human Anatomy
of a Small Planet. PLoS Medicine 4(1)13-18
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Global, neglected and most neglected diseases
(WHO MSF)
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Most neglected diseases(e.g. dengue, Chagas)
World pharmaceutical market(gt600 bn in 2005)
Neglected diseases(e.g. AIDS, malaria,
tuberculosis)
Global diseases(e.g. measles, diabetes)
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• Consequently in the last 30 years lt1 of the
  developed drugs were for LDC specific diseases

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RD for neglected diseases PPPs are changing the
field

• PPPs currently manage ¾ of neglected disease drug
  development projects
• The private sector is making more independent
  investments in neglected disease RD
• A quarter of neglected-disease RD is now being
  undertaken independently by large companies
• Four large pharma companies have founded formal
  neglected- disease divisions since 2000

Source Moran (2005) A breakthrough in RD for
Neglected Diseases New Ways to Get the Drugs We
Need. PLoS Medicine 2(9)e302.
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Why do we need New Prevention Technologies?Our
tools today are not enough to stop AIDS

• Over 39,5 million people infected with HIV and
• 11,000 new infections daily

• A comprehensive response is needed
• Deliver for today better use of tools
• Prevent further spread of the virus
• Treat and care for those already infected
• Mitigate social impacts
• Develop better tools for the future
• Invest in innovation for new technologies(drugs,
  diagnostics, microbicides, vaccines)

Better prevention tools particularly AIDS
vaccines - are critical for the affordability
and sustainability of our commitments to
universal access
Source UNAIDS 2006 Photos WHO/UNAIDS
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New adult HIV infections in low- and
middle-income countries
A vaccine could save millions of lives
Total new infections averted by an AIDS vaccine
between 2015-2030
IAVI impact forecasting Policy Brief 10,
November 2006
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Who needs an AIDS vaccine?

• All those who are at risk of HIV infection
• Especially people in the countries that are hit
  hardest by the AIDS epidemic
• Especially women, who need tools that they can
  control to protect themselves
• Especially teenagers and young adults, before
  they are sexually active or initiate the use of
  intravenous drugs

Global demand for an AIDS vaccine could reach 80
million doses per year
IAVI demand forecasting Policy Research Working
Paper 15, 2007
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So, is an AIDS vaccine possible? Yes !

• AIDS vaccines should
• Protect against HIV infection (sterilizing
  immunity)
• All routes of transmission, including
  intravenous, mucosal
• Protect against progression to disease
• Reduction of viral load
• Reduce transmission (infectiousness)
• Infected vaccinees likely to be lower or
  nontransmitters

• The immune system is able to
• control or protect against HIV
• Majority of PLW HIV initially suppress viral load
• Examples of populations resistant to HIV
  infection (e.g. Kenyan sex workers)
• Children of infected mothers
• Non-progressors control infection for many years
• Promising candidates in pipeline
• SIV infection
• Broadly Neutralizing Antibodies

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What is happening across the AIDS vaccine field?
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Around the world, 23 countries are conducting
AIDS vaccine trials (around 30 vaccine candidates
in development)
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AIDS Vaccines in Clinical Trials - 2007
Viral Vectors- Adenovirus Ad-5 (Clade
B) Merck Ad-5 (Clades A,B,C), DNA NIH-VRC Ad-6
(Clade B) Merck Viral Vectors- Pox Canarypox
(Clade B/E), gp120 Aventis MVA (Clade C)
IAVI-Therion MVA (Clade C) IAVI-ADARC MVA
(Clade B),fowlpox Therion MVA (Clade
B),DNA GeoVax MVA (Clade A/E), DNA WRAIR MVA
(Clade B/C Changchun Baike Fowlpox (Clade
B)MVA Therion NYVAC (Clade C)DNA EuroVac Vacci
nia (Cocktail) St. Judes Viral Vectors-
Other VEE (Clade C) AlphaVax formerly
IAVI AAV-2 (Clade C) IAVI-TGEN

• DNA vectors
• Clade C, IAVI-ADARC
• Clade B-minigenes Epimmune
• Clade B-nuclear anchor FIT Biotech
• Clade B, MVA GeoVax
• Multiclade-A,B,C, Ad5 NIH-VRC
• Clade B- Micro particle, gp140 Chiron
• Multiclade, gp120 U. Mass
• Multiclade-ABC, MVA Karolinska
• Clade C Johns Hopkins
• Clade B?C Changchun Baike
• Clade B/C, NYVAC EuroVac
• Clade B- IL12, IL-15, peptide Wyeth
• prime
• boost

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AIDS Vaccines in Preclinical Pipeline - 2007

• NIAID/CHAVI
• Chimeric Adeno Vectors
• BCG
• VSV
• CAVD BMGF
• Adeno Chimeric and Ad-11
• Pox NYVAC, MVA
• Low sero-prevalent AAV
• Reovirus
• Newcastle Disease
• HIV/VEE Chimeras
• HIV/VSV Chimeras
• BCG
• IAVI Vector Program
• Sendai
• CMV
• Simian Adeno (GSK)

In trials 2007-2009 Ad 35 prototype NIH-VRC Ad
35 IAVI-Crucell Chimeric Adeno Harvard-Crucell
VSV Wyeth Measles GSK MVA SAAVI WRAIR
Blue IAVI program
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The current pipeline is inadequate
Only hypothesis currently tested in pipeline is
cell-mediated immunity
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Political commitment is improved
"Whether it takes us 15 years, 20 years, 25 years
to get an AIDS vaccine, it is what will break the
back of the disease." - Melinda Gates
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More resources are being invested but more still
are needed, especially from Europe
Annual average by country relative to national
wealth (2003-2005)
Investment in AIDS vaccine RD
of GDP (x10-3)
Total over 2005 US759 mn
Country
United States
4.0 5.0
(none)
3.0 4.0
Ireland
2.0 3.0
Canada South Africa Netherlands
1.0 2.0
Norway United Kingdom
Denmark Sweden
0.5 1.0
Australia Brazil China Finland France Germany
India Italy Japan Russia Thailand
lt 0.5
Based on a 2006 study by the HIV Vaccines and
Microbicides Resource Tracking Working Group
full report available at www.hivresourcetracking
.org. The study reviewed national, not
sub-national or provincial, public sector data.
Cuba is not captured as no GDP data is available.
Estimates of 2005 investment include NIH CHAVI
funds.
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Developing a high-quality medicine is a complex
and expensive road










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The Global HIV Vaccine Enterprise
Funding Agencies
Scientists
Research Agencies
Shared Scientific Plan
NGOs Community groups
Biothech Pharma
International Organizations
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What is IAVIs role?
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IAVIs mission is to ensure the development of
safe, effective, accesible, preventive HIV
vaccines for use throughout the world
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IAVI, publicprivate product development
partnership since 1996
Access uptake
RD
Clinical trials
Production
Health other systems
Political will finance

• Research and development
• Fill the gap between between public sector basic
  research and commercial product development
• Develop vaccine candidates, prioritize the most
  promising ones and move them into clinical trials
• Policy and advocacy
• Ensure political and financial commitment
• Create a supportive environment for research
• Prepare for global access
• Engage developing countries
• Building capacity for RD
• Contribute to sustainable development of health
  infrastructure
• Involve communities, policy makers, politicians,
  media

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IAVIs niche in AIDS vaccine RD
Filling the gap between public sector basic
research and commercial product development
Public Sector
Biotech Pharma
Biotech Venture Capital
Preclinical and Clinical Trials
Basic Research
Applied Research
Large Scale Efficacy
Advanced Devel.
Early Product Devel.
Vaccine Design
Small Animal
NHP
Phase IIa
Phase I
Phase IIb
Phase III
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IAVI RD Resources

• New Technology Assessment
• Product Development Infrastructure
• Network of Partner-Sites in Developing World
• IAVI Human IAVI Immunology Lab
• Vaccine Development Lab

Neutralizing Antibody Consortium (NAC)
Vector Design Consortium (VEC)
Control of HIV/ SIV-Live Attenuated Consortium
(LAC)
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Vaccine discovery and development

• 11 clinical sites established in 5 countries in
  Africa and in India
• 17 clinical trials (phase I and II) with 907
  volunteers testing 6 vaccine candidates in 11
  countries in Africa, Asia, Europe and North
  America
• 7 clinical studies in Africa to assess
  feasibility of human trials, develop expertise at
  sites, and solve key immunological questions
• 3 scientific consortia to solve key scientific
  challenges in the development of new vaccine
  concepts
• 2 laboratories to support the scientific
  consortia and human trials, providing protocols,
  training, analytical services, etc
• 40 RD partnerships worldwide

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A global RD network, with a particular focus on
developing countries
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Partnership with developing countriesIAVIs
clinical trial network
IAVI India
Pune-NARI, India
Kangemi and KNH-KAVI, Kenya
Chennai-TRC, India
Entebbe-MRC, Uganda
IAVI East Africa
Masaka-MRC, Uganda
Kilifi-CGMRC, Kenya
Kigali-PSF, Rwanda
Lusaka-ZERHP, Zambia
Medunsa, South Africa
Cape Town-DTHC, South Africa
IAVI Southern Africa
Soweto, South Africa
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Product Development Prioritization of Candidates
Percent Positive Responders
Geometric Mean SFC/milion and Range of Responses
IAVI has 13 clinical trials completed 4 clinical
trials ongoing Total of 907 volunteers enrolled
in PI and PII trials in 11 countries
Vaccine response rate in vaccinees at peak post
vaccination timepoint per trial Core Laboratory
generated data GMT SFC and min max SFC for
responders background subtracted per 106 PBMCs.
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IAVI Clinical Research StudiesPrepare for
Efficacy Trials Inform Vaccine Design
P Fast, M Price, N Ketter, J Gilmour, etal
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The IAVI model working with developing countries

• An innovative approach to RD of an AIDS vaccine
  for nations that most need it
• Ensuring that vaccines will be available,
  accessible and used
• Using a development approach
• Create an enabling environment for research
• Promoting national ownership and sustainable
  in-country commitment
• Addressing the social and political context
  related to research in different cultural
  settings
• Building support and participation in research
• Bring the voices of developing countries to the
  global call for investment in AIDS vaccine
  research
• Mobilizing countries as integral to the process
• Supporting strong and well-informed developing
  country voices

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The IAVI model working with developing countries

• Use a development approach to RD
• Ensure that vaccines will be available,
  accessible and used
• Ensure sustainable research capacity and
  knowledge building
• Ensure the participation of national stakeholders
• Address social and political context related to
  research in different cultural settings
• Promote national ownership and in-country
  commitment
• Bring their voices to the global call for an AIDS
  vaccine
• Mobilize countries as integral to the process
• Supporting strong and well-informed developing
  country voices

Industrial-style RD within the context of
sustainable development and social responsibility
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An example(1) Site development
Uganda Virus Research Institute BEFORE Site of
Proposed UVRI-IAVI Lab Clinic
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UVRI-IAVI Lab Clinic in Entebbe, Uganda AFTER

• Lab/Clinic built
• LaboratoryValidated CMI assays, GLP training
• Accredited and now BMGF/CAVD reference lab

• Clinic Multiple Phase 1 HIV vaccine trials
  Accelerated approval and accelerated enrolment
  vs. historical controls
• Expansion Field sites doing incidence and other
  clinical studies in preparation for future
  efficacy trials

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An example(2) Training and education

• Vaccine Literacy
• Education programmes for
• Healthcare workers
• Counselors
• Community Advisory Board
• Community Workers

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An Example(3) Preparing for vaccine delivery
lessons from HPV vaccine introduction

• HPV vaccines can facilitate future introduction
  of AIDS vaccines infrastructure and lessons
• Targeting adolescents/pre-adolescents before they
  are sexually active
• Challenging the paradigm of delayed introduction
  in the developing world

• IAVI and PATH agreed in early 2007 to a
  collaboration around PATHs HPV Vaccine
  Evidence for Impact project

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PATH and IAVI strategic partnershipIntroducing
HPV vaccines in the developing worldbridging
reproductive health with the global response to
aids

• Objectives
• Country Introduction
• Implementing Research
• Testing Key aspects
• Strengthening Decision-making
• Policy Analysis
• Market, supply and demand analysis
• Develop decision-making tools
• Global Advocacy
• Coalition building
• Incorporating HPV vaccine in development agenda
• South-South cooperation

• Shared challenges for
• HPV and AIDS vaccines
• Targeting Adolescents
• Sexuality and Stigma
• Delivery Strategies
• Complex Messages
• Stakeholder Support
• Demand and Financing
• Rapid Introduction
• Women and Reproductive Health

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While important progress is being made, equally
important challenges remain
Issue
What it means

• HIV hyper-variability
• Immune correlates of protection are still unknown
• Relevant animal models lacking
• Clinical trials long and costly

• We are tackling a moving target
• Need to test in people
• Success will take time

Scientific

• Long term effort requires long term, high level
  global commitment - leading to action
• Market incentives for industry activity lacking
• Ethical, regulatory, IP issues
• Health systems challenges

• Until recently not a priority we need sustained
  political support
• Build private sector engagement
• Optimize environment for safe, ethical trials

Policy Political
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IAVIs Innovation Fund

• Your ideas
• Breakthrough technologies
• Novel immunogens e.g. bNAb, host targets
• Target novel immune mechanisms e.g. innate
  immunity
• New delivery modalities e.g. replicating vectors,
  mucosal delivery
• New ways to address key challenges e.g. from
  systems or computational biology
• Technologies that optimize existing candidates
• Adjuvants and formulation
• Antigen optimization
• Delivery technologies
• Prime-boost combinations
• Enabling technologies
• High throughput screening methodologies
• High throughput immunogen design

• Our offer
• Seed funding
• Non dilutive, targeted grants specifically
  designated for high-risk/high-reward technologies
  not funded through traditional HIV funding
  sources fast approval process
• Platform validation
• Feasibility of use in HIV vaccine RD
• Accelerated regulatory pathways
• Lower risk of investment in early phase
  technologies
• Opportunity for longer-term collaboration
• Funding partnership over the long haul
• IAVI experience (and infrastructure) with
  regulatory approval and clinical trials including
  in developing countries

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IAVIs public policy research activities

• Activity
• The business case
• Modeling the impact of AIDS vaccines
• Analyzing the potential demand for AIDS vaccines
• Supporting RD
• Regulatory and ethical approval for AIDS vaccine
  trials
• An advance market commitment (AMC) for AIDS
  vaccines
• Collateral benefits of vaccine trials
• The wider context
• AIDS and the Millennium Development Goals (MDG)
• Policy research and advocacy on gender issues

• Why are these important?
• Accelerate RD and future access
• Ensure adequate funding and human resource
  capacity
• Enhance global political and financial support
• Increase private sector and PPP engagement
• Build national commitment to AIDS vaccine
  research
• Build support for trials and future demand

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The road to a vaccine is long but there are
many achievements on the way, in the South
Healthcare workers who received training
National policies for HIV vaccine research
11 clinical labs sites in Africa and India

• Medical Ethical committees
• Standards of Care for volunteers
• Education for communities and journalists
• Voices from the south in the global arena
• And many others

27000 people who received VCT
Community and gender advisory boards
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And in the North
Global HIV Vaccine Enterprise
3 scientific consortia with scientists from
across the world
Innovation Fund
Financial commitment
Resource tracking
Political commitment
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We need your support

• To ensure that political commitment to AIDS
  vaccine RD is sustained for as long as needed
• To build an supportive environment with the right
  policies
• To raise sufficient financial support for AIDS
  vaccine RD for IAVI and for the field
• To address the remaining key scientific
  challenges
• To continue engaging developing countries and
  build sustainable capacity for research
• With as ultimate aim to accelerate the
  development of an AIDS vaccine that is accessible
  to all who need it

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A variety of incentives can stimulate development
and delivery by industry
PUSH Mechanisms reduce costs
PULL Mechanisms increase revenue

• Transferable IP rights
• Purchase Funds
• Advance Market Commitments
• Tax credits on sales
• Patent buyouts

• PDPPP support
• Fund for innovation
• Continued research subsidies/tax credits
• Fast-track review
• Milestone payments for RD breakthroughs
• Health systems development

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IAVIs policy research policies need to be
improved and an integrated approach is essential
In order to make available the resources
required to develop an effective AIDS vaccine an
enabling political environment and the correct
policy choices must be made
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IAVIs partners in Europe
Industry - Berna, Switserland - Crucell,
Netherlands - Cobra, UK - GSK Biologicals,
Belgium - Bioption, Sweden - FIT Biotech,
Finland - IDT, Germany - Transgene, France
AIDS organisations - AIDES, France - AIDS Fondet,
Denmark - Aidsfonds, Netherlands - Deutsche AIDS
Stiftung, Germany - El Grupo De Trabajo Sobre
Tratamientos Del VIH (gTt), Spain - Finnish
AIDS Council, Finland - HivNorge, Norway -
National AIDS Trust, UK - Noahs Ark, Sweden -
SENSOA, Belgium
Vaccine development

• Academia
• - Centre dImmunologie de Marseille-Luminy,
  France
• Imperial College, London, UK
• Karolinska Institute, Sweden
• Medical Research Council, Oxford, UK
• St. Georges University of London, UK
• University of Amsterdam, The Netherlands
• University of Oxford, London, UK

Advocacy mobilization
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IAVI gratefully acknowledges the support of our
donors