HIV Vaccine Development: An Industry Perspective

1. 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

2. 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

3. Conventional Vaccine Development Killed vaccines Cultivate Microorganism Live attenuated vaccines Subunit vaccines Test immunogenicity Test Convalescent sera Antigen selection Purify components 5-15years Identify components Clone genes 5-15 Years Pre-clinical POC/Pre-clinical Development Clinical Development/ Industrialization Vaccine

4. Inactivated Live, attenuated Subunit/rprotein Adjuvants (Limited) Inactivated Live, attenuated Subunit/rprotein (simple;complex) Vector-based Devices/alternate delivery Immunoadjuvants (targeted) Evolution in Vaccine Technologies 2020 2000

5. Vaccine R&D Timeline File Preclinical POC Launch DISCOVERY RESEARCH DEVELOPMENT REGISTRATION Many years 2-4 years 6-8 years 1 year 2 years continue • Identification of • target antigens • Understanding • of pathologies • Natural history • of disease • Done mostly outside • of the “Big Pharma” • 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 Industrial Investment

6. 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

7. 1984 – 1994 Recombinant envelope (rEnv) 1994 – 2003 T-cells based + rEnv (Prime-Boost) 2003 – Present Next generation T-cell based + Next generation rEnv Scientific “Waves” in HIV Development

8. 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

9. What is Proof of Concept? • Demonstrable vaccine-effect in Phase II study • Acquisition endpoint • Virological endpoint • Broadly reactive serum neutralizing activity against primary viral isolates

10. 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

11. Investment Hurdles • HIV Vaccine R & D challenges • Need for novel technologies • Significant global clinical development hurdles • Defining investment milestones • Challenges with increasingly complex partnerships

12. Industry R&D Clinical Trials Development of industrial capacity Manufacturing Financing: Industry gave: Tiered Pricing Public Sector Commitments to procure vaccines Infrastructure: Cold chain Storage facilities Clinical logistics Financing: Public sector/donors gave: Bulk purchasing Traditional Vaccine Development Model for Developing Countries Vaccine Development Purchase & Delivery

13. 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

14. 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

15. Partnerships Must Have a Shared Vision • Appropriate governance and communication is needed • Vaccine development is an iterative process • Failures will precede success • Success may be relative to specific populations; may require multi-component regimens • Addressing implications for impecfect early generation vaccines • It is important to discuss the role of industry now

16. No Company, Government or NGO Alone Will be Able to Carry the Burden Governments, 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.