Developing TB Vaccine Clinical Trial Capacity — Aeras Perspective

1. Developing TB Vaccine Clinical Trial Capacity — Aeras Perspective Vicky Cardenas, PhD, JD ASEAN-EU STI Days 21-23 January 2014

2. Aeras • Founded in 2003 • Mission: Develop improved TB vaccines that are affordable and accessible to all who need them • Offices • Rockville, MD (headquarters) • Cape Town, South Africa • Beijing, China • Governed by a Board of Directors • Technical advisory groups incorporating expertise from around the world • ~ 170 total employees with annual budget of approx. USD $50 million 2

3. Fully Integrated R&D Capabilities • Clinical Research • Network of clinical trial partner sites in North America, Europe, Africa and Asia • Diagnostic and mycobacteriology lab capacity at sites • Highly trained and skilled clinical research infrastructure with offices in USA, South Africa & China • Preclinical Research • Staff expertise in vaccine design, assay development, immunology, animal studies, antigen selection, platform development, patent and regulatory filings • Process Development & Manufacturing • Fully integrated BSL-2 compliant biopharmaceutical manufacturing facility 3

4. Collaboration is key in an unprecedented effort Aeras serves as a catalyst byinvesting in the world’s most promisingTB vaccine candidatesand coordinating a diverse community of global scientists, researchers, governments, and funders on a single mission:the development of effectiveTB vaccines. 4

5. TB is a Global Epidemic with an Urgent Need for Action • Nearly 9 millionnew cases globally every year • 11 countries in the Asia Pacific are among the 22 countries that carry 80% of • the global TB disease burden 5

6. Disease burden in Asia Pacific Source: WHO, Global Tuberculosis Control Report 2013 6

7. TB will not be eliminated by 2050 Current rate of decline -2%/yr (globally) China, Cambodia -4%/yr (the best observed nowadays) Today TB incidence >100x higher than elimination target for 2050 W Europe after WWII -10%/yr (Historical example) Elimination target:<1 / million / yr -20%/yr 7

9. Vaccine development approach – where to focus 9

10. Aeras’ Discovery Portfolio 10

11. The Global Pipeline of TB Vaccine Candidates PHASE I PHASE IIa PHASE IIb PHASE III VIRAL VECTOR rBCG PROTEIN/ADJUVANT ATTENUATED M.Tb IMMUNOTHERAPEUTIC: Mycobacterial – Whole Cell or Extract AERAS SPONSORED 11

12. Clinical Trials Ongoing and Completed Since 2003 • Numerous clinical trials in Africa, Asia, Europe, and North America 12

13. Historically…circa 2000 • Aeras focus on South Africa • high TB incidence • 576/100k in 2000 • 1003/100k in 2013 Report • large population • ~45 M in 2000 • ~52.5M in 2013 Report • TB Control program • sites requiring some TB capacity building • experienced researchers 13

14. Expansion Period 2005-2009 IPHCR Pune, India Makerere University Iganga, Uganda KEMRI/CDC Siaya, Kenya CHC SvayRieng, Cambodia UCT/SATVI; Worcester, South Africa 14

15. Strategy shift circa 2009 • Funder interest in bricks and mortar development, and longitudinal cohort studies diminished • BMGF funding for cohort studies stopped • Sites sought different funding streams to complete follow up 15

16. Methods shift (I) • Expand search to regions traditionally unexplored for conduct of TB vaccine clinical trials • Identify high incidence pockets in medium incidence countries • Network to identify TB researchers working in the area • Identify established experienced clinical trial sites requiring no/little infrastructure development 16

17. Methods shift (II) • Determine TB and TB/HIV epidemiology through focused review of extant data (global, national, local, published, etc.) • If appropriate, collaborate on collection of data through conduct of epidemiological studies • Conduct assessment of capacity needs for participation on TB vaccine trials (refer to Pre-Qualification Visit questionnaire) 17

18. Clinical Study Sites Aeras partners globally to conduct epidemiological studies and clinical trials. 18

19. Recent Partnership Efforts in Epidemiology and Site Capacity 19

20. Aim: Add ASEAN countries 20

21. Major Funders and R&D Partners