AIDS VaccinesAdvancing Development through Innovation

Frans van den BoomVice President IAVI European Programmes

24 October 2007

Helsinki, Finland

Understanding global inequalities

Private health spending Malaria cases

Dorling D (2007) Worldmapper: The Human Anatomy of a Small Planet. PLoS Medicine 4(1)13-18

2

Global, neglected and most neglected diseases (WHO & MSF)

3

World pharmaceutical market(>$600 bn in 2005)

Most neglected diseases(e.g. dengue, Chagas)

Neglected diseases(e.g. AIDS, malaria,

tuberculosis)Global diseases

(e.g. measles, diabetes)

Consequently in the last 30 years <1% of the developed drugs were for LDC specific

diseases

R&D for neglected diseases: PPPs are changing the field

Source: Moran (2005) A breakthrough in R&D for Neglected Diseases: New Ways to Get the Drugs We Need. PLoS Medicine 2(9):e302.

• PPPs currently manage ¾ of neglected disease drug development projects

• The private sector is making more independent investments in neglected disease R&D

A quarter of neglected-disease R&D is now being undertaken independently by large companies

Four large pharma companies have founded formal neglected-disease divisions since 2000

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

Why do we need New Prevention Technologies?

Our tools today are not enough to stop AIDS

Source: UNAIDS 2006Photos: WHO/UNAIDS

New adult HIV infections in low- and middle-income countries

Total new infections averted by an AIDS

vaccine between 2015-2030

30% efficacy, 20% coverage 5.5 million

17 million50% efficacy, 30% coverage

70% efficacy, 40% coverage 28 million

0

1

2

3

4

5

2000 2005 2010 2015 2020 2025 2030

New

Infe

ctio

ns (M

illon

s)

Vaccine introduction

Base

Low scenario

Medium scenario

High scenario

A vaccine could save millions of lives

IAVI impact forecasting; Policy Brief #10, November 2006

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

What is happening across the AIDS vaccine field?

Around the world, 23 countries are conducting AIDS vaccine trials (around 30 vaccine candidates in development)

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

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

Vaccinia (Cocktail) St. Jude’s

Viral Vectors- Other

VEE (Clade C) AlphaVax [formerly IAVI]

AAV-2 (Clade C) IAVI-TGEN

NIAID/CHAVIChimeric Adeno Vectors

BCG

VSV

CAVD BMGFAdeno: Chimeric and Ad-11

Pox: NYVAC, MVA

Low sero-prevalent AAV

Reovirus

Newcastle Disease

HIV/VEE Chimeras

HIV/VSV Chimeras

BCG

IAVI Vector ProgramSendai

CMV

Simian Adeno (GSK)

AIDS Vaccines in Preclinical Pipeline - 2007

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

The current pipeline is inadequate

Only hypothesis currently tested in pipeline is cell-mediated immunity

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

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.

Total over 2005 = US$759 mn % of GDP (x10-3)

Country

4.0 – 5.0

2.0 – 3.0

1.0 – 2.0

0.5 – 1.0

< 0.5

Ireland

United States

CanadaSouth AfricaNetherlands

NorwayUnited

KingdomAustralia

BrazilChina

FinlandFrance

Germany

IndiaItaly

JapanRussia

Thailand

3.0 – 4.0 (none)

DenmarkSweden

Annual average by country relative to national wealth (2003-2005)

More resources are being invested …but more still are needed, especially from Europe

Investment in AIDS vaccine R&D

DiscoveryDiscovery

Exploratory DevelopmentExploratory Development

Full Full DevelopmentDevelopment

RegistrationRegistration

Large Amounts ofCandidate Medicine

Synthesized

Project Teamand Plans Synthesis

of Compounds

EarlySafety

Studies

CandidateFormulations

Developed

ExtensiveSafety

Studies

Screening

Studies in HealthyVolunteers Phase I

Candidate Medicine Tested in3-10,000 Patients (Phase III)

Studies in 100-300Patients (Phase II)

Clinical DataAnalysis

$$$

$$

$

$$$$

Developing a high-quality medicine is a complex and expensive road

What is IAVI’s role?

IAVI’s mission is to ensure IAVI’s mission is to ensure the development of safe, effective, the development of safe, effective,

accesible, preventive HIV vaccines for accesible, preventive HIV vaccines for use throughout the worlduse throughout the world

IAVI, public–private product development partnership since 1996

Research and developmentFill the gap between between public sector basic research and commercial product developmentDevelop vaccine candidates, prioritize the most promising ones and move them into clinical trials

Policy and advocacyEnsure political and financial commitmentCreate a supportive environment for researchPrepare for global access

Engage developing countriesBuilding capacity for R&DContribute to sustainable development of health infrastructureInvolve communities, policy makers, politicians, media

Political will & finance

R&D Clinical trials

Production Health & other systems

Access & uptake

IAVI’s niche in AIDS vaccine R&D

Preclinical and Clinical Trials

Small Animal

BasicResearch

Applied Research

Large Scale Efficacy

Advanced Devel.

Early Product

Devel.

Vaccine Design

NHP Phase IIaPhase I Phase IIb Phase III

Public SectorBiotechPharma

Biotech Venture Capital

Filling the gap between public sector basic research and commercial product development

IAVI R&D Resources

•New Technology Assessment

•Product Development Infrastructure

• Network of Partner-Sites in Developing World

•IAVI Human IAVI Immunology Lab

•Vaccine Development Lab

•

•

NeutralizingNeutralizingAntibodyAntibodyConsortiumConsortium(NAC)(NAC)

Vector DesignVector DesignConsortiumConsortium(VEC)(VEC)

Control of HIV/Control of HIV/SIV-Live AttenuatedSIV-Live AttenuatedConsortium (LAC)Consortium (LAC)

A global R&D network, with a particular focus on developing countries

Kilifi-CGMRC, Kenya

Entebbe-MRC, UgandaChennai-TRC, India

Medunsa, South Africa

Soweto, South Africa

IAVI East Africa

IAVI Southern Africa

Kangemi and KNH-KAVI, Kenya

Masaka-MRC, Uganda

Kigali-PSF, Rwanda

Lusaka-ZERHP, Zambia

Cape Town-DTHC, South Africa

Pune-NARI, India

IAVI India

Partnership with developing countriesIAVI’s clinical trial network

Product Development: Prioritization of Candidates

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.

DNA

Oxford

2mg

DNA

ADARC

3X4mg

DNA

VRC

3X4mg

AAV

TGC

1x1011

MVA

Oxford

5x107

MVA

ADARC

2.5x108

MVA

Therion

2.5x108

Adeno

VRC

1x1010

6% 17% 49% 20% 5% 62% 92% 46%

35 69 109 130 57 130 80 101

31-40 66-73 44-598 54-385 41-79 55-275 39-193 52-297

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

Protocol Summary Status

A HIV prevalence Completed: n=6500

B HIV incidence 4800 enrolled

CHIV early infection & HIV control study

> 150 enrolled

D Laboratory reference rangesCompleted: n= 2400 enrolled

E PBMC processing logistics Completed

F Potential vector seroprevalence Completed

G Neutralizing antibodies Underway

H Protocol C in vaccine recipients In development

IAVI Clinical Research Studies:Prepare for Efficacy Trials & Inform Vaccine Design

P Fast, M Price, N Ketter, J Gilmour, etal

The IAVI model: working with developing countries

Use a “development” approach to R&D

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 R&D 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

<#>

UVRI-IAVI Lab & Clinic in Entebbe, Uganda [AFTER]

Lab/Clinic built

Laboratory:Validated 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

Vaccine Literacy

Education programmes for:

Healthcare workersCounselorsCommunity Advisory BoardCommunity Workers

An example:(2) Training and education

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 PATH’s “HPV Vaccine: Evidence for Impact” project

PATH and IAVI strategic partnershipIntroducing HPV vaccines in the developing world:

bridging 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

While important progress is being made, equally important challenges remain

HIV hyper-variability

Immune correlates of protection are still unknown

Relevant animal models lacking

Clinical trials long and costly

Scientific

We are tackling a moving target

Need to test in people

Success will take time

Issue What it means

Policy &Political

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

IAVI’s Innovation Fund

Your ideas

Breakthrough technologiesNovel immunogens e.g. bNAb, host targetsTarget novel immune mechanisms e.g. innate immunityNew delivery modalities e.g. replicating vectors, mucosal deliveryNew ways to address key challenges – e.g. from systems or computational biology

Technologies that optimize existing candidates

Adjuvants and formulationAntigen optimization Delivery technologiesPrime-boost combinations

“Enabling technologies”High throughput screening methodologiesHigh throughput immunogen design

Our offer

Seed fundingNon 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 R&DAccelerated regulatory pathwaysLower risk of investment in early phase technologies

Opportunity for longer-term collaborationFunding & partnership over the long haulIAVI experience (and infrastructure) with regulatory approval and clinical trials including in developing countries

IAVI’s public policy research activities

ActivityThe ”business case”Modeling the impact of AIDS vaccinesAnalyzing the potential demand for AIDS

vaccines

Supporting R&DRegulatory and ethical approval for AIDS

vaccine trialsAn advance market commitment (AMC)

for AIDS vaccinesCollateral benefits of vaccine trials

The wider contextAIDS and the Millennium Development

Goals (MDG)Policy research and advocacy on gender

issues

Why are these important?

Accelerate R&D 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

The road to a vaccine is long … but there are many achievements on the way, in the South

Medical Ethical committees Standards of Care for

volunteers Education for communities

and journalists Voices from the south in the

global arenaAnd many others …

11 clinical labs & sites in Africa and India

Healthcare workers who received training

27000 people who received VCT

National policies for HIV vaccine research

Community and gender advisory boards

And in the North

Global HIV Vaccine Enterprise

Financial commitment

3 scientific consortia with scientists from across the world

Innovation Fund

Resource tracking Political commitment

We need your support …

To ensure that political commitment to AIDS vaccine R&D is sustained … for as long as needed

To build an supportive environment with the right policies

To raise sufficient financial support for AIDS vaccine R&D 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

IAVI’s partners in Europe

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

- Noah’s Ark, Sweden

- SENSOA, Belgium

Academia

- Centre d’Immunologie 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

Industry

- Berna, Switserland

- Crucell, Netherlands

- Cobra, UK

- GSK Biologicals, Belgium

- Bioption, Sweden

- FIT Biotech, Finland

- IDT, Germany

- Transgene, France

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Vaccine development

Advocacy & mobilization

IAVI gratefully acknowledges the support of our donors