1 Vaccine Development: From the Lab to the Clinic Jim Tartaglia, PhD Vice-President, R & D Sanofi Pasteur AIDS Vaccine 2011 Bangkok, Thailand September 12, 2011

2 HIV Vaccine Development: An Industry Perspective Key Messages HIV vaccine development follows same principles as with other vaccine efforts HIV vaccine development has certain unique hurdles HIV vaccine development/deployment requires public/private partnerships

3 Vaccines – How Do They Differ from Drugs? Biologicals vs. Chemicals Preventative rather than therapeutic Considered by many to be commodities Impacts compliance, willingness to pay and acceptance of side effects

4 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

5 Vision for New Vaccines Clear, shared understanding of the future: Disease Impact/Public-health need Epidemiology, morbidity, mortality and socio-economic impact Demand Realistic product profile, production & presentation Realistic assessment of development costs and timelines Clear vision of future demand, price and financing Realistic assessment of public-health value, in the context of other preventive measures Political Will Shared commitment to need, priorities, demand, price and cost Partnerships Risk sharing Leveraging resources and expertise

6 Elements of a Target Product Profile (TPP) Indications Populations Geographical coverage Route of administration Presentation Co-administration Post-license activities

7 Vaccine R&D Timeline Many years2-4 years DISCOVERYRESEARCH Antigen production Assay development Animal model dev. Preclinical tox Preclinical POC 6-8 years DEVELOPMENT 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 1 year 2 yearscontinue REGISTRATIONLCM Launch File Identification of target antigens Understanding of pathologies Natural history of disease Done mostly outside of the “Big Pharma”

8 Vaccine Development Decision Gates

9 Goals of Pre-Clinical Development Know your product Vaccine candidates should be appropriately characterized to insure material can be consistently produced Is the product safe ? Vaccines are given to healthy individuals, especially pediatric populations, limited tolerance to adverse events Is the product immunogenic in animals? Is the product effective in animal models?

10 Clinical Development Plan (CDP): Vaccine formulation Recommended vaccination schedule (primary course, booster) Safety Immunogenicity Efficacy

11 Phases of CDP: Phase I Phase IIa Phase IIb Phase III

12 HIV Vaccine R & D Challenges Need for novel technologies/complex regimens Significant global clinical development hurdles Interplay between clinical research and clinical development Defining investment milestones Challenges with increasingly complex partnerships Strict traditional industry development paradigm is insufficient

13 Sustained industry partnership for all components is essential to success It is imperative to secure industry partnership to ensure a cohesive strategy for: Product profile Regulatory strategy Clinical supply Approaches to access

14 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.