Thomas G. Evans, MD
Aeras’s mission of pursuing affordable and globally effective vaccines for tuberculosis (TB) is at the core of everything we do. That is because each of us at Aeras is keenly aware of the tremendous toll TB takes on the world, causing 4100 deaths every day.
Achieving this mission requires a multifaceted approach, guided by our strategic imperatives and founded upon global partnerships. Aeras is committed to strengthening our relationships with stakeholders and seeking out new collaborations with academic institutions, nonprofit organizations, pharmaceutical and biotech companies, and governments that can bolster our work with scientific expertise, technology, resources and funding. We must develop a more diverse and robust portfolio of vaccine candidates using time- and resource-efficient strategies. We also must raise awareness that more than 2 billion people—one-third of the world’s population—are infected with Mycobacterium tuberculosis (M.tb.), the bacteria that cause TB, culminating in 9 million new cases of TB and 1.5 million deaths each year.
In 2014, we made great progress on these fronts. Aeras and GlaxoSmithKline (GSK) initiated a large Phase 2b clinical trial of our most advanced vaccine candidate, M72/AS01E, to assess its ability to prevent TB in high-risk adults. Such a vaccine could have a rapid and dramatic impact because adolescents and adults are the major transmitters of TB and bear the majority of the burden of the disease. Even with an efficacy rate of just 60 percent with a 10-year duration of protection, M72/AS01E delivered to just 20 percent of adults and adolescents globally could prevent approximately 50 million cases of TB in its first 25 years of use. By interrupting transmission, this vaccine could potentially prevent more TB in young children than the same vaccine delivered as a boost to BCG in newborns, and do so in a cost-effective manner, as suggested in a study published last year in the Proceedings of the National Academy of Sciences.
Other accomplishments include the launching of a novel Proof of Concept, Prevention of Infection trial of the H4:IC31 vaccine or BCG revaccination in adolescents in South Africa, in collaboration with Sanofi Pasteur; managing consortia to develop a human challenge model of TB and to assess the potential for antibody-based vaccines; and achieving promising results from several vaccine studies in an enhanced nonhuman primate model. Aeras also co-sponsored three major international workshops to address key scientific issues: aerosol delivery of TB vaccines, Whole Mycobacterial Cell Vaccines, and TB vaccine development to prevent M.tb. Infection.
Aeras continues to raise awareness of the threat of TB through our award-winning documentary films, websites, social media efforts and media outreach. This past year we were encouraged by President Obama’s executive order that directs the U.S. Department of Health and Human Services and other relevant agencies to increase resources toward combating drug-resistant diseases, including TB. This initiative will raise the profile of drug-resistant TB, which sickened more than 480,000 people worldwide in 2013, and optimally result in greater emphasis to counter this problem, including support for TB vaccine development.
We are encouraged by progress in 2014 and are grateful for the support of our many partners and collaborators. We firmly believe that together we can achieve our shared goal of eradicating TB as a global health emergency.
Thomas G. Evans, M.D., Chief Executive Officer
Ann M. Ginsberg, M.D., Ph.D., Chief Medical Officer
Jacqueline E. Shea, Ph.D., Chief Operating Officer
Aeras Executive Team
Targeting resources towards the most promising candidates from a portfolio of options is critical to achieving our ultimate goal of developing a universally available and effective TB vaccine. Created with the help of a wide range of partners and stakeholders over the last few years, our portfolio management process is transparent, data-driven and based on rigorous science. A dedicated team reviews all internal and external candidates according to predetermined criteria that include novelty, superiority, technical feasibility and expected safety. The Aeras Portfolio Review Committee then uses these recommendations to create and manage a diverse portfolio of candidates and concept-driven studies to maximize probability of success.
Aeras and its partners are pursuing a wide variety of new antigens, models, assays, adjuvants, platforms, and routes of delivery at the preclinical stage of research:
Aeras is working with several partners to explore this promising vaccine delivery method to enhance mucosal immunity. Aeras and CREATE Vaccine Company, Ltd. are working together to develop new mucosal TB vaccines based on the National Institute of Biomedical Innovation, Health, and Nutrution’s (NIBIOHN) human parainfluenza type-2 (rhPIV2) vector technology. Aeras is also collaborating with researchers at the University of Pittsburgh and Wuhan University in China to evaluate aerosol delivery of vaccines in nonhuman primates. In April 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a workshop on aerosol TB vaccines, drawing expertise from Europe, China, Canada, South Africa and the United States.
The Oregon Health & Science University (OHSU) and associated Vaccine and Gene Institute is leading a collaboration with Aeras and the Bill & Melinda Gates Foundation (BMGF) to develop a promising TB vaccine candidate using a cytomegalovirus (CMV) backbone that induces novel immunologic responses and has shown promise in initial non-human primate studies.
Aeras is collaborating with a large number of academic and biotechnology partners to develop a “natural” transmission model in animals, which can then be used to evaluate vaccine candidates that may work through antibody or other immunologic mechanisms different from those induced by most vaccines presently being tested in the clinic.
Aeras, INSERM and the TuBerculosis Vaccine Initiative (TBVI) jointly advanced development of a new adjuvanted recombinant protein candidate, heparin binding hemagglutinin antigen (HBHA), with a unique mechanism of action. Further studies, including detailed product characterization and functional investigations, were undertaken in 2014, along with process development to create a final cGMP manufacturing process in anticipation of going to first-in-man studies.
Aeras works with partners to develop novel BCG and TB strains that might be used in developing human challenge models, and supplies reagents and standardized antigen cassettes to be used in discovery programs throughout the world. A consortium to standardize a functional readout to measure vaccine efficacy, the mycobacterial growth inhibition assay (MGIA), continues in efforts to find better correlates of protection.
Aeras and GlaxoSmithKline Vaccines (GSK) initiated in 2014 a large, multi-country, Phase 2b clinical trial of GSK’s proprietary protein-adjuvant vaccine candidate M72/AS01E. This candidate has already been extensively evaluated in early human and animal studies and is now being assessed in the clinic for its ability to prevent TB in healthy adults. The study is enrolling more than 3,500 healthy adults between the ages of 18 and 50 with latent TB infection who live in South Africa, Kenya and Zambia. Ten percent of subjects were successfully enrolled by the end of 2014, ahead of the targeted recruitment rate. Results of this double-blind, randomized, placebo-controlled study are expected to be available in 2018.
A groundbreaking Phase 2 clinical trial of the TB vaccine candidate H4:IC31 and of BCG revaccination is currently underway in South Africa. With Aeras as the regulatory sponsor and conducted by the South African Tuberculosis Vaccine Initiative (SATVI), this is the first study to evaluate, as a proof of concept, that the H4:IC31 vaccine has important biological activity in humans and has the ability to prevent sustained infection by M.tb. (the bacteria that cause TB). Studies that measure the prevention of TB disease typically are larger, longer and more expensive than this study of 990 healthy adolescents, which will provide quicker results with fewer subjects. If a vaccine demonstrates the ability to prevent sustained M.tb. infection, it indicates a high probability of success that it will be able to prevent disease and ultimately break the cycle of transmission.
A large study of the safety and immunogenicity of the MVA Ag85A vaccine was undertaken in almost 2800 infants over the past 4 years, and the results reported in Lancet Infectious Diseases in early 2015. Although the vaccine did not show any greater efficacy than BCG alone, the field learned important lessons from this study and correlates of risk are being discovered. The trial results also led to the downsizing of a second trial of the same vaccine - in HIV+ adults, enabling redirection of resources and minimizing subject enrollment.
Also in 2014, we completed the first large trial of an adenoviral-based vaccine in over 400 infants. An adaptive trial design enabled us to choose not to expand the trial to enter the efficacy phase when the vaccine did not meet pre-specified immunogenicity criteria. We also supported a critical study of the combination of these two vaccines in adults, and showed that the combined use of an adenoviral-based vaccine followed by an MVA-based vaccine was safe and resulted in more robust immunologic responses than seen with either vaccine alone. This exciting result sets the stage for future evaluation of combination vaccine approaches in animals and man.
Aeras co-sponsored three major international workshops to address key scientific issues:
Aeras and the National Institute of Allergy and Infectious Diseases held this workshop in Bethesda, Maryland, in April to explore the potential for developing aerosol vaccines capable of preventing M.tb. infection or active TB disease, or as immunotherapy for persons with active TB. Members of the workshop emphasized the need for greater support to further explore the potential of this delivery methodology, either alone or as an adjunct to traditional parenteral methods of vaccine administration.
Aeras and the Max Planck Institute for Infection Biology convened this workshop in Berlin in July, to discuss progress in the development of TB vaccines based on whole mycobacteria cells. Workshop participants concurred that the use of whole mycobacteria cells as TB vaccine candidates merits greater support, particularly given the limited understanding of the specific M.tb. antigens necessary to generate an immune response capable of preventing M.tb. infection.
Aeras and the National Institute of Allergy and Infectious Diseases held this conference in Rockville, Maryland, in November, to explore the biologic plausibility, potential public health and economic impact, and regulatory feasibility in attempting to develop a vaccine to prevent sustained infection with M.tb. Pursuing a prevention of sustained M.tb. infection indication for TB vaccines, in parallel with ongoing efforts to develop vaccines to prevent active TB disease, was deemed a potentially important effort, but would require further resources, particularly to improve diagnostic assays, to increase the regulatory feasibility of this endeavor.
Aeras scientists contributed to advancing the field by authoring numerous articles published by scientific journals in 2014.
Aeras’s Africa office in Cape Town is an essential component of our efforts to develop an effective, affordable TB vaccine. Our Africa-based staff plays leading roles in preparing for and implementing clinical trials, ensuring the needed laboratory capacity, and overseeing trial data management.
Aeras’s office in Beijing serves as an important base for developing relationships throughout Asia, which are critical to advancing TB vaccine research and development.
In addition to advancing science to develop new TB vaccines, Aeras’s work includes raising awareness about the dangers and global impact of tuberculosis. Ensuring that individuals, communities and governments are knowledgeable about this deadly disease will help affected people get the treatment they need, decrease transmission rates, and encourage country leaders and donors to invest resources in finding an effective TB vaccine.
TB Unmasked is a multifaceted campaign to raise awareness of the profound dangers faced by healthcare workers on the front lines of the TB epidemic. Launched at the 2014 Union World Conference on Lung Health in Barcelona, the campaign includes a series of short films depicting moving stories of healthcare workers; a website with profiles of healthcare professionals, guidelines for protection, expert resources, the opportunity for people to tell their own stories; and social media tools. By showing how so many selfless individuals have risked their health—some even losing their lives—to help patients suffering from TB, the TB Unmasked campaign emphasizes the need to find a vaccine for this deadly disease. Warmly received by the global TB community, TB Unmasked is on pace to be Aeras’s most-watched video.
Aeras continued its efforts to raise awareness about the tuberculosis crisis in the mines of southern Africa, where nine out of 10 miners are infected with M.tb. African mines are associated with about one-third of all new TB cases in Africa each year. Designing better prevention programs and working toward an effective vaccine are essential to battling this deadly epidemic, which is costing governments and the mining industry $360 million a year on treatment alone.
First launched in 2013, “EXPOSED: The Race Against Tuberculosis,” a four-part series of short films created to raise awareness of the TB epidemic, continues to make an impact. By focusing on the personal experiences of four people who’ve been affected by TB and interspersing their stories with the expert commentary of physicians, scientists, advocates and policymakers, EXPOSED depicts the severe impact and the enormous scope of the TB problem in order to promote the need for new tools to prevent the spread of the disease. EXPOSED has won numerous awards, including recognition from the American Business Awards, PRNews’ Digital PR Awards, The Online Film Festival and the Best Shorts Competition. The EXPOSED website has received more than 10,000 visits and the video series has been viewed 12,000 times on YouTube.
Aeras continues to garner attention from media outlets worldwide and to expand our reach as advocates for devoting the time, energy and funds needed to address the scourge of TB. In 2014, Aeras was featured in numerous news articles that reached millions of people around the world.
Aeras is a nonprofit, global biotech advancing the development of new TB vaccines for the world, in partnership with other biotech, pharmaceutical, governmental and academic organizations. With offices in the U.S., Africa, and Asia, Aeras represents a widely recognized critical mass of expertise in TB and vaccine development, and functions as a “translational machine” to ensure critical scientific findings are developed into vaccine products to prevent TB. Working with our extensive network of partners and funders, we can effectively manage and prioritize vaccine candidates to accelerate progress in TB vaccine research and development. As a nonprofit we develop and champion TB vaccines based on global need and science, rather than profit, and we work to ensure that the final product is affordable and accessible to those living in the developing world where TB vaccines are most needed.
In addition to our mission, Aeras is guided by these six strategic imperatives:
*Discontinued Operations reflect the net financial results of the Aeras Contract Manufacturing and Process Development operations which were sold in 2015 and no longer operated by Aeras effective June 2015.
Aeras is grateful to the leaders who contributed to the strength of the organization in 2014.
Former Senior VP
and CFO of MedImmune, Inc.
Distinguished Service Professor at Harvard University
and Joan L. and Julius H. Jacobson Professor of Public Health
Former President & CEO of Aeras
Senior Advisor, Research and Innovation
Ministry of Health, The Netherlands
CEO of Aeras
Covington & Burling,
and Lecturer, Harvard Law School
Former Dean and Emeritus Professor of Paediatrics & Child Health Faculty of Sciences,
University of Cape Town
UN Secretary-General’s Special Envoy on HIV/AIDS in Eastern Europe and Central Asia
President and CEO of Vaxinnate
ExxonMobil Malaria Scholar in Residence, Harvard School of Public Health
Former CEO of Intercell AG
Chief Executive officer
Chief Medical Officer
Chief Operating Officer
Chief Human Resources Officer
Chief Financial Officer
Business & Corporate Development
Clinical Development South Africa
VP of Technical Operations
Vaccine Advisory Committee
Aeras’s Vaccine Advisory Committee (VAC) provides external expert advice on criteria for vaccine candidate selection, preclinical stage-gating, and priorities for advancing candidates in preclinical and clinical portfolios. The VAC, which meets at least twice a year, advises Aeras on a broad range of crucial product development issues including: development plans, regulatory strategy, epidemiology studies, innovative clinical trial designs and downstream market considerations.
Professor of Medicine
Division of Infectious Diseases & Medical Microbiology
McGill University Health Centre
Head, Takeda Development
Chief Medical Officer
Chief, Clinical Trials Core
Chief, Viral Pathogenesis Laboratory
Vaccine Research Center, NIAID, NIH
HIV & TB Team
Bill & Melinda Gates Foundation
Global Head, Vaccines Research
Novartis Vaccines & Diagnostics
Director & Principal Investigator
Desmond Tutu HIV Centre
Institute of Infectious Disease, University of Cape Town
Fleming Professor of Medical Microbiology
Imperial College London, and
Head of Division of Mycobacterial Research
MRC National Institute for Medical Research
Chief Medical Officer
Biomarkers and Correlates Working Group
The Biomarkers and Correlates Working Group (BCWG) reviews progress in the field of correlates and biomarkers, including gaps and new developments in the field. The group also helps design Aeras studies and advises on funding needs.
President and Director
Seattle Biomedical Research Institute
Bill & Melinda Gates Foundation
Chief, Laboratory of Parasitic Diseases
National Institute of Allergy and Infectious Diseases (NIAID)
Chief of the Tuberculosis, Leprosy and other Mycobacterial Diseases Section within the Respiratory Diseases Branch of the Division of Microbiology and Infectious Diseases (DMID) National Institute of Allergy and Infectious Diseases (NIAID)
Vice President, Scientific Affairs
Associate Professor, Department of Molecular Genetics and Biochemistry
University of Pittsburgh School of Medicine
Head, TB Research Group
Veterinary Laboratories Agency
Deputy Director, TB Vaccines
Bill & Melinda Gates Foundation
Deputy Director, Global Health Discovery & Translational Sciences Program
Bill & Melinda Gates Foundation
Director of the Department of Immunology
Max Planck Institute for Infection Biology
Professor in Immunology
Head group Immunology and Immunogenetics of Bacterial Infectious Diseases
Dept. of Infectious Diseases
Leiden University Medical Center
Associate Professor and Deputy Director, Immunology
South African TB Vaccine Initative
University of Cape Town
Aeras’s successes are only possible through collaborations and partnerships. Aeras gratefully acknowledges these important donors and R&D partners, along with the numerous other collaborators, including clinical trial participants and site staff, not listed here that make our work possible: