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HIV Vaccine Development: An Industry Perspective

Jim Tartaglia, PhD

Vice-President R & D

sanofi pasteur, Ltd.

Toronto, Canada

XVI International AIDS Conference

A World Without AIDS: The Long Road to Effective HIV Vaccines

August 15, 2006

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HIV Vaccine Development: An Industry Perspective

Industry is….Committed to the global efforts to develop an HIV vaccine(s)

Open to evolving public-private partnerships that aim to facilitate R & D efforts for HIV vaccines globally

Receptive to novel access paradigms that aim to ensure the delivery of effective HIV vaccines to the people who need them most and in a timely fashion

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Conventional Vaccine Development

Pre-clinical POC/Pre-clinical Pre-clinical POC/Pre-clinical DevelopmentDevelopment

Clinical Development/ Clinical Development/ IndustrializationIndustrialization

Test Convalescent

sera

Antigen selection

5-15 Years

Cultivate Microorganism

Clone genes

Test immunogenicity

Purify components

Identify components

Vaccine

5-15years

Killed vaccines

Live attenuated vaccines

Subunit vaccines

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Evolution in Vaccine Technologies

Inactivated

Live, attenuated

Subunit/rprotein

Adjuvants (Limited)

Inactivated

Live, attenuated

Subunit/rprotein (simple;complex)

Vector-based

Devices/alternate delivery

Immunoadjuvants (targeted)

2000 2020

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Vaccine R&D Timeline

Many years 2-4 years 6-8 years 1 year 2 years continue

DISCOVERY RESEARCH DEVELOPMENT REGISTRATION

• Antigen production• Assay development• Animal model dev.• Preclinical tox

Phase I•Safety•Initial•immunogenicity

Phase II a• Dose finding• Dose/schedule

finding• Immunogenicity

Phase II b• Early POC

Phase III• Large scale

safety +• Lot to lot

consistency +• Non inferiority

(combos) or• Efficacy

LaunchPreclinical

POC

Industrial Investment

File

• Identification of target antigens

• Understanding of pathologies

• Natural historyof disease

• Done mostly outside

of the “Big Pharma”

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Challenges Facing the Vaccine Industry

Success of vaccines – people no longer fear many diseases

Consumers expect perfect vaccines

Highly effective

No side effects

Increased complexity and difficulty of regulatory environment

• Increased cost and length of development

• Increased resource drain associated with maintaining marketed products

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Scientific “Waves” in HIV Development

1984 – 1994 Recombinant envelope (rEnv)

1994 – 2003 T-cells based + rEnv (Prime-Boost)

2003 – Present Next generation T-cell based + Next generation rEnv

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Vaccine Development is Iterative

Research Development Commercial

‘Proof of concept’ in humans is a key milestone

Several candidates are tested before the right one is identified

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What is Proof of Concept?

Demonstrable vaccine-effect in Phase II studyAcquisition endpointVirological endpoint

Broadly reactive serum neutralizing activity against primary viral isolates

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Even After Proof of Concept in Humans.. Many Questions Remain

‘Vaccine effect’--Clinical significance of surrogate endpoint

Genetic background

Risk profile

Mode of transmission

Subtype-specificity

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Investment Hurdles

HIV Vaccine R & D challenges

Need for novel technologies

Significant global clinical development hurdles

Defining investment milestones

Challenges with increasingly complex partnerships

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Traditional Vaccine Development Model for Developing Countries

IndustryR&D

Clinical Trials

Development of industrial capacity

Manufacturing

Financing:

Industry gave:Tiered Pricing

Public SectorCommitments to procure vaccines

Infrastructure:Cold chain

Storage facilities

Clinical logistics

Financing:Public sector/donors gave:

Bulk purchasing

Vaccine Development Purchase & Delivery

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R&D

Development of industrial capacity

Clinical trial partnerships

Manufacturing capacity

Access to IP and technology

Regulatory Capacity

Demand Estimates

Improvements in delivery infrastructure

Commitment to purchase vaccines at acceptableprices and for an acceptable term

To ensure a vaccine will be delivered as quickly as possible, industry, the public sector, NGOs and donors must work simultaneously, in partnership

Global Responsibility

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A Model for Ensuring Access

Partnerships among industry, the public sector and donors

with guarantees of purchase, regulatory harmonization, tax

credits and other incentives for industry to manufacture

vaccines for developing countries

Greater access to technology or bulk product for eligible

countries with technical capacity

New regional regulatory approaches

New regional plants: Industry or publicly-owned

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Partnerships Must Have a Shared Vision

Appropriate governance and communication is needed

Vaccine development is an iterative process Failures will precede successSuccess may be relative to specific populations; may require multi-component regimensAddressing implications for impecfect early generation vaccines

It is important to discuss the role of industry now

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No Company, Government or NGO Alone Will be Able to

Carry the BurdenGovernments, academia, NGOs, donors and industry

must work together to allow for the most effective means for developing and providing access to a vaccine(s) for

those who need it the most, as quickly as possible.