Transcript francis
Entrepreneurial Thought Leaders Seminar Donald P. Francis, MD, DSc Presentation Outline I. Myself – a brief description II. Vaccines – Social need, business challenge III. The company/mechanisms to develop vaccines IV. Lessons, reality, future directions An Entrepreneur by Necessity • California physicians: Grandfather, mother, father • Trained in pediatrics and infectious diseases • 21 years with CDC as infectious disease epidemiologist • Cholera Nigeria • Smallpox Sudan, India, Bangladesh • Ebola Sudan • AIDS everywhere • Since 1992, an AIDS vaccine “Entrepreneur” • Co-founded what became Int’l AIDS Vaccine Initiative • Genentech • Co-founded VaxGen (1995) • Now developing a not-for-profit for developing country vaccines. How Do Vaccines Work? • Vaccines “fake out” the immune system • Without causing disease, they induce a “post-infection” immune status • Protection from subsequent infection or disease Mortality rate per 100,000/year Infectious Disease Mortality Rates in the U.S. 40 Diptheria Pertussis Measles Poliomyelitis AIDS 30 20 10 0 1900 1920 1940 1960 Year 1980 People Living with HIV/AIDS Sub Sarahan Africa 22,500,000 South and South-East Asia 6,700,000 Eastern Europe, Central Asia 270,000 East Asia and Pacific 560,000 Australia and New Zealand 12,000 North America 890,000 Caribbean 330,000 Latin America 1,400,000 N. Africa, Middle East 210,000 Western Europe 500,000 Total: 33.4 million Source: UNAIDS, AIDS Epidemic Update, Dec. 1998 AIDS Orphans in Sub-saharan Africa "By the year 2010, one in seven children under 15 years will have lost a parent to AIDS." Annual Direct Medical Costs of HIV for the World $18 billion in 1997* *Modified from AIDS in the World II, ed. Mann & Tarantola An HIV/AIDS Vaccine The only way to stop the AID epidemic is with a vaccine Challenges Business Scientific Social value How Many Candidate HIV Vaccines Could Be Funded by One Year's Direct Medical Costs? $ 18.0 billion $ 0.3 billion (medical costs) (develop. costs) 61 candidate vaccines HIV-1 Vaccine Development Pipeline or pipette? Phase I Phase II Phase III 27 candidates 2 candidates 1 candidate "Maybe in the next 10 years if we work very hard, there may be 3 candidate vaccines in PhaseIII." Dr. Jose Esparza, UNAIDS March, 1999 Cost of HIV Vaccine Development 400 300 Investors cost 200 100 Company revenue 0 0 2 4 6 Years 8 10 Opportunity Costs Huge social need Questionable return ? Market (esp developing countries) ? Social value (demand?) Why Vaccines Fail to Compete Vaccine/Therapeutic Market Comparison Note: Vaccine market data 2000, pharma sales 2001 Development of Vaccines vs Anti-viral Agents for HIV Historical Dev Time Social Demand Num Available Anti-viral Vaccines Anti-viral Drugs Many Longer Low None Few Shorter High Many HIV Prevalence vs GNP VaxGen’s Vaccine Almost 20 years $280MM invested A long way to go AIDSVAX Development History AIDSVAX research begins IIIB produced Chimps protected (IIIB) Nucleotide squence of HIV determined Chimps protected (MN) B/B and B/E produced IIIB Phase I MN Produced Antibodies to rgp 120 neutralize HIV MN Phase I 85 86 87 88 89 90 Genentech, Inc. B/E Phase I/II B/B Phase III Trial Antibodies Inhibit binding to CD4 84 B/B Phase I/II MN Phase II 91 92 93 B/E Phase III Trial 97 98 99 00 01 VaxGen, Inc. 02 03 AIDSVAX –Cost of Development Capital Sources: Investment: Genentech $ 50M Private capital: $269M VaxGen $130M US Government: $11M1 Celltrion $100M ______ $280M NGO $0 _____ Total $280M Total 1 Includes CDC and NIH Efficacy Trial Results Thai trial – no efficacy US/Europe Trial – Low efficacy AIDSVAX B/B - Efficacy by Subgroups 100% Weighted cohort Efficacy 77.6% 86.5% 65.7% 50% 5.8% 0% Overall Volunteers (vacc + plcbo) *Expected infections, VE=0 Observed infections (vacc) p-value (unadjusted) Black Women 5009 194 191 498 33 12 314 17 4 268 8 1 NS <0.01 <0.02 NS *Adjusted for 2:1 vaccine:placebo VaxGen – Built a Company with Value • > 120 highly-skilled vaccine developers • Excellent team spirit • Flexible VaxGen - Looking Ahead • Company following “social value” - Priority shift to anthrax and smallpox • Future AIDSVAX development will require outside funding/partnerships NIH/CDC collaboration to complete analysis NIH - Subtype C vaccine – early stage NIH - Thailand prime-boost Phase III trial The Next Venture • Three VaxGen senior executives stepping out of company • Will establish a not-for-profit foundation • Pursue vaccine development for the lessdeveloped parts of the world • Dependent on outside (Gates) funding