1. Progress in TB Vaccine Development
GLOBVAC 2017 Conference
Trondheim, Norway
Dereck Tait
14 March 2017

2. Our Mission
Developing new safe and effective TB vaccines that are affordable and accessible to all who need them
Staff Notes:
Mission: Developing new safe and effective TB vaccines that are affordable and accessible to all who need them

3. Overview of Aeras Nonprofit founded 1997
Rockville, MD, USA (headquarters)
Cape Town, South Africa
Beijing, China
Product Development Partnership
Translational expertise and capabilities from candidate optimization to late stage trials
STAFF NOTES: (can address mission here, depending on slides used)
Nonprofit biotechnology organization or Nonprofit TB vaccine R&D organization
About 90 employees
Technical advisory groups incorporate expertise from around the world

4. Aeras Africa: Areas of Focus
Clinical trials
Community Engagement programs
Laboratory capacity development
Policy and advocacy
Staff Notes:
Clinical trials, including strategy and site development
Community Engagement Programs
Laboratory capacity development
Policy and advocacy

5. World’s population estimated at ~7.4 billion
One third are infected with Mtb
10% of those infected will develop active TB
10.4 million developed active TB
IN 2015
1.8 million died from the disease
490,000 were women
210,000 were children
Animation: 4 clicks.
1) Changes light blue people to dark to represent 1/3 population with Mtb
2) adds 10% with active TB
3) brings strip about 2014
4) adds the “top 5 killer”
Sources: WHO Global TB Report 2016

6. BCG Vaccine Has Not Stopped Epidemic
Staff Notes:
In use since 1921
Infants and children
Prevents severe forms of TB
Modest and variable protection against primary infection and pulmonary TB
Doesn’t adequately protect teens and adults, who are most likely to spread TB
Most used vaccine in the world, but has not controlled the epidemic
Photo note: image is from istock.com (Aeras has rights for “editorial,” non-commercial purposes).

7. Reaching SDG & WHO elimination targets requires a new TB vaccine
Drugs with shorter regimens for treatment
Improved point-of-care diagnostics
New TB vaccine
Will defeat TB
Staff note: this is the static version, I adjusted a little bit of the spacing so use this one.
Global strategies (WHO, SDGs) to end TB rely on new tools, including better:
Drugs
Diagnostics
Vaccines
A new TB vaccine that is safe, effective and affordable would be:
Cost effective and sustainable solution to eliminate TB
Core component to address the global crisis of drug-resistant TB
Easily implemented within existing health systems
WHO’s End TB Strategy
Targets include reducing TB deaths by 95% by 2035
Global Plan to Stop TB
5-year plan for the WHO End TB Strategy, with milestones
Calls for significantly increased funding for R&D
UN Sustainable Development Goals
SDG 3.3: “By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases”
Ellen to Jacqui: If you like this slide, we can animate it.
Source: WHO Health Assembly 2014

8. TB is “a cornerstone of the global AMR challenge”
Review on Antimicrobial Resistance, May Lord Jim O’Neill, Chair
Source: WHO TB Report, 2015.
ELLEN to Jen: I need to find the updated map from the 2016 report, label the map, and update the source

9. = Drug Resistance Vaccine Resistance Staff Notes:
Animation: 1 click brings in not-equal-to icon.

10. TB Vaccine R&D is Severely Underfunded
$250 million: Annual funding needs1
Only about $110 million invested per year,
Only receives a sixth of funding for HIV vaccines2
2 funders provide 65% of global resources2
Annual global cost of TB: $20 billion
$8 billion total TB control cost burden3
$12 billion economic impact (lost productivity, wages)4
Sources: 1. Stop TB Partnership. The Global Plan to End TB ; 2. G-Finder 2015; 3. WHO. Global TB Report 2015; 4. WHO. Trade, foreign policy, diplomacy and health; Tuberculosis Control

11. New TB Vaccines are Achievable
Human immune response
Latency
Reverters and resisters
BCG vaccine provides partial protection
Scientific progress
Refined NHP models
CMV-TB
Game changers: CHIM & functional assays
A more diverse early-stage pipeline
Novel clinical trial designs

12. Target Patient Populations
Prevent TB disease in adolescents and adults
BCG replacement in infants
Staff Notes:
Prevent TB disease in adolescents and adults
- Aeras priority
- Major source of Mtb transmission
- Key to reaching the End TB 2035 goal of TB elimination
BCG replacement in infants
- Aeras cooperates with efforts, but does not lead

13. Global Clinical Pipeline of TB Vaccine Candidates
Phase 1
Phase 2a
Phase 2b
Phase 3
MTBVAC
Biofabri, TBVI, Zaragosa
RUTI
Archivel Farma, S.L
DAR-901
Dartmouth
VaccaeTM
Anhui Zhifei Longcom
Ad5 Ag85A
McMaster, CanSino
H1/H56: IC31
SSI, Valneva, Aeras
VPM 1002
SII, Max Planck, VPM, TBVI
ChAdOx1.85A/MVA85A
Oxford, Birmingham
H4: IC31
Sanofi Pasteur, SSI, Aeras
M72 + AS01E
GSK, Aeras
MVA85A/MVA85A (ID, Aerosol)
Oxford
ID93 + GLA-SE
IDRI, Wellcome Trust, Aeras
Viral Vector
TB/FLU-04L
RIBSP
Protein / Adjuvant
Mycobacterial – Whole Cell or Extract
Static version (no animation)
Pipeline overview, key points to make:
13 candidates; 10 years ago, only 1
3 platforms
Lack of immunological diversity (all “classical” CD4 and CD8)
Revised on October 7, 2016
Please note: Information is self-reported by vaccine sponsors

14. Approaches to Streamlining Clinical Development
Conduct Pre- and Proof-of-Concept trials in high-risk populations
Use Phase 2 trials to establish “plausible biological effect”
Decreasing:
Risk
Cost
Time
Staff Notes
Conduct Pre- and Proof of Concept trials in a high-risk populations
QFT+ adults
Healthcare workers
Recently cured TB patients
Household contacts
Use Phase 2 trials to establish “plausible biological effect”
Prevention of (established) Infection (POI)
8X risk
Prevention of Recurrence (POR)
4-5X risk

15. TB Vaccines in Phase 2 or 3 Vaccine Endpoint Data Due Vaccae® (China)
Prevention of Disease
2017
M72
(South Africa; Kenya; Zambia)
Mid 2017
H4:IC31
(South Africa)
Prevention of Infection
Early 2018
H56:IC31
(South Africa; Tanzania)
End 2019

16. GLOBVAC Funded Aeras Studies
Epidemiology Study - Incidence of TB and mortality in a cohort of Indian BCG vaccinated neonates
Funding – GLOBVAC; University of Bergen; Aeras
Phase 1 Clinical Study – Safety and Efficacy of AERAS-402 in healthy adults (India)
Funding – GLOBVAC; Aeras
Phase 2 Clinical Study – Prevention of Mtb Infection in adolescents (Tanzania; South Africa)
Funding – GLOBVAC; Aeras; SSI; Wellcome Trust

17. GLOBVAC Funded Studies
Preparing for tuberculosis vaccine efficacy trials: Baseline epidemiology, improved diagnosis, markers of protection and phase I/II trials.   RCN (179342)  
Funding: RCN, Aeras, St John’s Research Institute, Bangalore, India
Preparing for tuberculosis vaccine efficacy trials: Identifying at-risk individuals for TB vaccine trials. RCN (192534)
Partners UoB, Aeras and St John’s Research Institute, Bangalore, India 
Funding - RCN
Phase 2 Clinical Study – Prevention of Mtb Infection in adolescents (Tanzania; South Africa). RCN (248042)
Funding – RCN; Aeras; SSI; Wellcome Trust

18. Summary TB is a global health emergency
TB Vaccines are challenging but achievable
TB Vaccines essential to ending epidemic
Adolescents and adults are key target populations – major impact on epidemic
13 TB vaccines in clinical development
Phase 1 – 3
Pre-clinical and experimental medicine advances
Data from four phase 2 or 3 studies mid-2017 to early-2019

19. Recent Major Funders and R&D Partners
And special thanks to the sites and participants in our clinical trials!

20. Current Clinical Sites and Networks