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

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

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

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

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

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).

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 2016-2020 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

TB is “a cornerstone of the global AMR challenge” Review on Antimicrobial Resistance, May 2016. 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

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

TB Vaccine R&D is Severely Underfunded $250 million: Annual funding needs1 Only about $110 million invested per year, 2010- 20142 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 2016-2020; 2. G-Finder 2015; 3. WHO. Global TB Report 2015; 4. WHO. Trade, foreign policy, diplomacy and health; Tuberculosis Control

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  

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

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

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

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

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

GLOBVAC Funded Studies Preparing for tuberculosis vaccine efficacy trials: Baseline epidemiology, improved diagnosis, markers of protection and phase I/II trials.   RCN (179342) 2009-2014  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) 2012-2016 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) 2016-2021 Funding – RCN; Aeras; SSI; Wellcome Trust

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

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

Current Clinical Sites and Networks