Vaccines for Diseases of Poverty The Translational Gap

1
Vaccines for Diseases of PovertyThe
Translational Gap

• Adrian V. S. Hill
• The Jenner Institute
• Oxford University

2
SUMMARY

• There is a huge translational gap in funding
  vaccines between research and later stage
  clinical development
• Europe has great strengths in vaccinology
• This is wasted because European governments
  neglect funding vaccine development

3
THE PROBLEM

• TRANSLATION
• TRANSLATION
• TRANSLATION

4
Situation Analysis

• Unacceptable morbidity and mortality from
  malaria, tuberculosis, HIV/AIDS
• Huge funding of basic research in immunology,
  pathogen biology, animal models
• Billions of euros!
• Unprecedented opportunities for vaccine
  development
• Field sites waiting for a vaccine
• - new support from EDCTP

5
Strengths in Europe

• Outstanding research in academia /public sector
• Pasteur SSI Oxford Max-Planck Karolinska
• Leading companies
• Sanofi-Pasteur GSK Bio Novartis Crucell
• Leading technologies
• lipopeptides poxvirus vectors gene gun
  adjuvant formulations TLR agonists simian
  adenoviruses new cell lines prime-boost
  strategies reverse vaccinology
• Unique links with African partners
• Commitment to capacity development

6
Obstacles

• Lack of any business case for vaccine companies
  to invest in TB, malaria, HIV
• Very difficult science
• High risk investment
• Long term approach required
• Clinical assessment of new vaccine approaches
  essential
• Animal models all have limitations

7
Another Challenge

• Vaccine companies are getting bigger
• GSK
• Sanofi-Aventis
• Merck
• Wyeth
• Novartis
• So products must be ever more valuable to be of
  interest
• big companies will generally only in-license
  after phase II

8
Implication

• Public sector investment is required
• But European governments fail on this
• compared to US
• compared to Foundations

9
Malaria Vaccine RD Expenditures(US Dollars in
thousands)
2003 budget figures are projected, all others
are actual Euro converted on 1.0 exchange
rate (Figures from The Wellcome Trust to be
included in the near future)
Accelerating vaccine development to save lives
10
Who Should Be Funded?

• FP6-style consortia
• Non-profit research institutes
• Companies
• large and / or small
• Public Private Partnerships

11
Public Private Partnerships

• Why not leave funding these all to the Gates
  Foundation?
• Assets of 30bn last month
• Now more than doubled gt 60bn
• Arent they doing a great job?

12
The Gates Foundation Vaccines for The Big Three

• HIV
• Initially IAVI
• Recently GHAVE
• Malaria
• Malaria Vaccine Initiative at PATH (MVI)
• TB
• Sequella, now renamed AERAS

13
Aeras Global TB Vaccine Foundation

• Established in 2004 with 83m grant from Gates
  Foundation
• Fully competent non-profit biotech model
• Manufacturing, clinical development, field sites
• Not a funding agency
• Seek exclusive world-wide IP rights
• Currently seeking to in-license all the leading
  TB vaccine candidates

14
New TB Vaccines in the Clinic

• 2002 MVA85A (Oxford University)
• 2004 rBCG-30 (not being developed further)
• 2004 72f / AS02 (Corixa / GSK)
• 2005 Hybrid / IC31 (SSI)

15
A Multi-Stage Malaria VaccinePutting the Pieces
Together
Sporozoite Stage
RTS,S GSK Biologicals
Liver Stage
ME-TRAP Oxford University
Blood Stage
AMA-1 NIH, BPRC MSP-1 WRAIR MSP-3
Institut Pasteur
16
Gates Foundation Investment in Vaccines for the
Big Three

• An unprecedented investment
• major supporter of three PPPs
• Less leverage of other funding than had been
  hoped
• But relatively little progress on addressing the
  translational gap

17
How Could Europe Do Better?

• Adequate resources
• Unlike EMVI
• Science-based
• rather than product-based
• Focus on concept testing
• Aim for multi-component vaccines
• many technologies may be required
• Avoid pandering to large companies

18
What the Problem is NOT!

• Manufacturing
• GCP compliance
• Regulatory compliance
• Clinical development strategy
• Intellectual property
• Access to technologies

19
The Challenge is Scientific

• It will be solved by translational scientists
• We do not know how to make a highly effective
  HIV, malaria or TB vaccine
• which antigens / immune response / delivery
  system
• But there are many possible options, which
  require clinical evaluation
• the challenge is to assess these options as
  rapidly as possible, realising that most will
  fail
• this is very different to drug development

20
ACTION REQUIRED

• Adequate levels of investment
• Public sector investment from Europe comparable
  to the US
• Science-based evaluation of funding modalities

21
SUMMARY

• There is a huge translational gap in funding
  vaccines between research and later stage
  clinical development
• Europe has great strengths in vaccinology
• This is wasted because European governments
  neglect funding vaccine development