TuBerculosis Vaccine Initiative

P.O. Box 65 8200 AB Lelystad The Netherlands

T +31 (0) 320 238960 F +31 (0) 320 238050 E [email protected]

Chamber of Commerce 09180367 www.tbvi.eu ANNUAL REPORT 2008 Making TB a disease of the past ANNUAL REPORT 2008 CONTENTS

Foreword 5 Making TB a disease of the past

Tuberculosis 7 One death every eighteen seconds

TBVI 11 Working together to conquer TB

TB R&D in Europe 15 Greater investment in research

Fundraising & Advocacy 19 Opening doors and finding sympathetic ears

TBVI in action 23 Bridging the gap

Organization 27

Partners 33

Donors 35

Financial Report 37 FOREWORD

Making TB a disease of the past

In the summer of 2007, Hannu Laang and Ole Olesen ten years. These resources will be used to stimulate scientific of the European Commission were the first to suggest discovery, to facilitate early clinical development of new the establishment of a separate entity to fund research vaccines, and to find biomarkers that indicate the potential for new vaccines to conquer tuberculosis. Less than success of vaccine candidates at an early stage. TBVI a year later, on 5 March 2008, Tuberculosis Vaccine aims to link scientific discovery and preclinical development Initiative or TBVI was established, a European based with industrial product and clinical development; to bridge foundation facilitating development of safer and more the gap between research and development. effective vaccines against tuberculosis. TBVI’s first year was mainly directed at establishing rela- In the years preceding the establishment of TBVI, thanks tions with governments, NGOs and industry. At the time of to EU funding and the combined efforts of the TBVAC writing this foreword, the first donations are coming in. We partners we had made excellent progress (TBVAC is an are extremely happy with the support of the EC and with integrated EU project). However, much work remained to the recent approval of the NEWTBVAC project to succeed be done and far more funding would be required for deve- TBVAC for the next four years. We’re delighted with the loping new vaccines. The STOP-TB partnership estimated support of the Bill and Melinda Gates Foundation, which a global requirement of 1.5 billion dollars for 2006-2015. enables us to conduct our advocacy and fundraising ac- To bridge the gap, we had to find other donors besides tivities for the next three years. Finally, we have secured European Union institutions. With financial support from the support of our first industrial donor, FIT Biotech. governments, non-governmental organizations and private industry, we could finance more scientific discovery, re- In the coming years, TBVI strives to support research and search and development. development in research centers all over Europe. Financially and practically. If we can generate sufficient resources TBVI was established using the infrastructure we laid and successfully join scientific research and industry, we down for TBVAC, and with assistance from the EU and might see the dawn of an era in which TB really is a dis- Wageningen University & Research Centre among others. ease of the past. TBVI consists of broadly the same partners that joined forces for TBVAC. The main goals of TBVI are to continue Jelle Thole, Director TBVI the international consortium of research institutes and to generate additional funding of € 200 million over the next

5 TUBERCULOSIS

One death every eighteen seconds

Far from being a disease of the past, tuberculosis cent risk of developing the disease in later life. People claims millions of victims each year. Around one third with HIV run a much higher risk; they are twenty times of the earth’s population is infected, resulting in over more likely to develop the symptoms once they are 9 million new cases and close to 2 million deaths an- infected. nually. With new infections occurring at a rate of one per second, Tuberculosis, or TB, is a common and often deadly infec- millions of people develop TB symptoms every year. In tious disease. It is caused by mycobacteria, mostly Myco- 2007, there were 9.27 million new cases, up from 8.3 million bacterium tuberculosis in humans. Tuberculosis spreads in 2000 and 6.6 million in 1990. Over half these cases are through the air when individuals who have the disease in Asia, predominantly China, India and Indonesia. Africa cough, sneeze or spit. A single sneeze can release up to is also heavily affected, with about a third of new cases. 40,000 droplets, each of which can transmit the disease. Particularly South Africa and Nigeria count many victims. In 2007, around 1,750,000 people died from tuberculosis. Tuberculosis usually attacks the lungs, but can also affect One in four deaths is HIV-related. other parts of the body, such as the lymphatic system, the central nervous system and the circulatory system. The Multiple drugs treatment classic symptoms of pulmonary TB are a chronic cough TB is treated with (a combination of) antibiotics to kill the with blood-tinged sputum, chest pain, fever and weight bacteria. However, whereas a treatment of one or two loss. Infection of other organs causes a wide range of weeks suffices for many other diseases, TB requires symptoms. Infection usually starts in the lungs. The bacteria much longer periods of treatment, up to a year. The best multiply and spread through the body through the results are obtained with DOTS, directly observed treatment, lymphatic system and the bloodstream. short-course. This involves observed treatment with four drugs for two months, followed by treatment with two One in three infected drugs for another four months. However, if the treatment About one third of the world’s population is infected with is prematurely ended or if the patient does not adhere to Mycobacterium tuberculosis. However, most will not get the prescribed regimen, the bacteria might become drug- ill. Only about one in ten infected people will develop clinical resistant. Drug-resistant TB poses an increasing problem. symptoms within one to two years. In most other individuals, About 5 per cent of the new cases of prevalent TB are a latent infection develops, with an approximately 10 per multidrug-resistant, that is, resistant to front-line DOTS

7 A disease of all ages drugs. Fifty-five countries have reported cases of exten- facing TB. The main goal is to dramatically reduce the Tuberculosis has been around since antiquity. Skeletal sively drug-resistant TB (XDR-TB). XDR-TB strains are global burden of tuberculosis by 2015 by ensuring that all remains have shown that prehistoric man suffered from resistant to both front line and second line anti-TB drugs. TB patients, including for example, those co-infected with TB, and tubercular decay has been found in the spines of HIV and those with drug-resistant TB, benefit from universal mummies from 3000 to 2400 BC. Hippocrates reported Control of tuberculosis is based upon two main pillars. access to high-quality diagnosis and patient-centered around 460 BC that tuberculosis was the most widespread Firstly, detection of individuals with TB in their sputum and treatment. The strategy also supports the development of disease of his time. subsequent treatment using DOTS. Secondly, children new and effective tools to prevent, detect and treat TB. are vaccinated with BCG to protect them against TB. BCG The Stop TB Strategy underpins the Stop TB Partnership’s The study of tuberculosis dates back to ‘The Canon of was developed between 1905 and 1921 at the Pasteur Global Plan to Stop TB 2006-2015. Medicine’ written by Ibn Sina in the 11th century. He iden- Institute in France. A century later, it is still the only vaccine tified pulmonary tuberculosis as a contagious disease and available. In children, the vaccine is highly effective was the first to suggest that it could spread through contact against disseminated TB and TB meningitis. However, BCG with soil and water. On 24 March 1882, Robert Koch is much less effective against pulmonary TB, especially in identified and described the bacillus causing tuberculosis: adolescents and adults. Furthermore, the vaccine may mycobacterium tuberculosis. In 1905, Mr. Koch received seriously harm children who are infected with HIV. the Nobel Prize for his discovery.

Stop TB Partnership In 1908, French immunologists Camille Guérin and Albert In 1988, the Stop TB Partnership was established to combat Calmette at the Institut Pasteur started developing a vac- TB. Its aim is to halve the global burden of TB disease cine against TB. It would be called BCG (Bacille Calmette- relative to 1990 levels by 2015 and to eliminate TB as a Guérin). The BCG vaccine was first used in humans in However, in the developing world, many people still public health issue by 2050. The Partnership comprises France in 1921, but is was not until after World War II that fell victim to TB each year. The worldwide occurrence international organizations, countries, donors from the BCG was widely accepted and used, reducing the occur- of TB increased again from 124 per 100,000 (1990) to public and private sectors, governmental and nongovern- rence of TB considerably. 142 per 100,000 (2004). Since then, it has decreased mental organizations and individuals who have expressed slowly to 139 per 100,000. In Asia and Africa especially, an interest in working together to achieve this goal. The disease was further constrained by a steady improve- more than 4000 people die from the disease each day. ment in hygiene, sanitation, diagnosis and treatment. In HIV co-infection and the increasing incidence of drug- The World Health Organization (WHO) has developed a Europe, the number of deaths from TB steadily declined. resistant strains challenge current control programs. new six-point Stop TB Strategy, which builds on the success People were even inclined to think that tuberculosis had New diagnostics, drugs and vaccines are essential to of DOTS, while also explicitly addressing the key challenges been eradicated. effectively control, and eventually eliminate TB.

9 5 TBVI

Working together to conquer tuberculosis

TBVI was set up to raise additional funds for TB Joint ownership with partners research and to maintain and strengthen international TBVI leaves responsibility and ownership of each vaccine scientific cooperation in finding new TB vaccines. candidate to individual partners. They have the freedom to operate and establish partnerships for (late) clinical TBVI is a non-profit organization that supports and facili- development at the opportune moment. TBVI offers a tates a growing network of over thirty universities, institutes separate interface where individual partners can exchange and industries. Since 2000, most of these organizations information with private industry on the progress of their have used their R&D creativity, excellence and synergy to vaccine candidates. Part of each agreement for support translate research and discovery into product and (early) from TBVI is a commitment from partners to aim for vac- clinical vaccine development. TBVI seeks financial support cines that are accessible and affordable to the developing for TB research and development from governmental world. organizations, non-governmental organizations and private industry. Their contribution greatly enhances the chances of finding new TB vaccines.

Supervision from leading experts The portfolio is managed by the TBVI Steering Committee, which is composed of leading experts in the field of TB vaccine development. The Steering Committee decides on support for new developments and new steps in the progression of vaccine candidates and other products from discovery to preclinical and clinical phases. The advancement of each product is supervised and guided by product development teams and clinical development teams. TBVI’s Steering Committee is composed of leading experts in the

field of TB vaccine development 11 Uniting researchers and sponsors

Transparent structure Dedicated to cooperation TBVI has found a home at the Animal Sciences Group, Funded by public means and private donations, TBVI has TBVI is dedicated to international cooperation. Founded in part of Wageningen University and Research Centre put much effort into a transparent structure. The Steering Europe, TBVI also aims to work together with organizations (ASG). ASG hosted the coordination of TBVAC, the Committee ensures that funds are distributed on the basis with similar objectives from other continents. For instance, EU-funded research pr ogram that preluded TBVI. of agreed criteria and in accordance with the strategic TBVI cooperates with its US counterpart, Aeras. Whereas Possessing extensive experience with large research plan. In 2008, all decisions taken by the Steering Committee TBVI is primarily active in the earlier stages of vaccine programs and international academic cooperation, were unanimous. Daily activities, advocacy & fundraising development, Aeras is also involved in the later stages of ASG was the ideal organization to keep all parties and the development teams are directed by the Operational clinical development. The two organizations complement aligned in support of the goals of TBVAC. Office based in Lelystad, the Netherlands. one another. Ultimately, we share the same vision: to conquer tuberculosis. ‘When the creation of TBVI was suggested, we imme- diately came on board and made our expertise available’ Founded in Europe, TBVI also says Mr. Dick Pouwels, member of the TBVI Governance aims to work together with Board. ‘We’re delighted to have TBVI within our walls. We can utilize our expertise to further promote and organizations with similar advance European academic cooperation.’ objectives from other continents ‘A big challenge is to channel more public and private funding into the most promising scientific projects’, Governance Board says Mr. Pouwels. ‘Most scientists are not very skilful The Governance Board verifies the coverage of financial in attracting financial means. Their core business is resources for projects proposed by the Steering Committee. TBVI objectives research; that’s what they are good at. On the other The Board also appoints members of the Steering 1. Stimulate research and discovery on TB vaccines hand, sponsors don’t always have the expertise to Committee and the Board of Trustees and employees of 2. Assure preclinical and early phase clinical development assess the scientific and medical merits of research the Operational Office. The Board of Trustees has two 3. Guarantee that promising projects result in affordable projects. It’s therefore difficult for them to determine types of members: representatives of donor organizations vaccines as soon as possible where their funding can best contribute. TBVI has already and high-representatives. In addition to financial support, 4. Develop biomarkers that will increase performance proven its added value with the TBVAC-project, and donor organizations provide strategic advice. High-repre- and speed of vaccine development as a credible non-profit organization, TBVI is able to sentatives act as ambassadors for TBVI, ideally providing 5. Increase capacity of existing clinical trial sites in bring researchers and sponsors together.’ the foundation with access to their network. developing countries

13 TB R&D IN EUROPE

Greater investment in research

Prof. Paul-Henri Lambert is one of the leading experts, if not the leading expert in vaccinology, as well as the author of several books on the subject. According to Prof. Lambert, TBVI is essential in promoting and fa- cilitating international academic cooperation.

Prof. Lambert is the Director of the International Advanced Course of Vaccinology at the University of Geneva and he was closely involved with TBVAC. He currently chairs the TBVI Steering Committee and is a member of the Gover- nance Board.

‘TBVI is bridging a gap’, says Prof. Lambert. ‘Europe has built a strong position in the field of TB research. However, most of this research consists of EU-funded projects. There is no continuity. TBVI provides a structure that gives continuity and permanency to international academic co- operation. Furthermore, it links the academic world with ‘The pipeline must be filled. industry.’ Therefore, we must invest more

‘It is essential that sufficient resources are made available in research’ for research and development. Cooperation within TBVAC has resulted in some significant candidates, but we don’t ‘Another important area is the quest for biomarkers as yet know whether they are any good for long-term protec- biological indicators of the efficacy of newly developed tion. Besides, we need several types of vaccines. One vaccines. We don’t have appropriate biomarkers at present that gives initial protection, one to boost adolescent and this means that we must perform extensive clinical immunity, one for preventing relapses in exposed individuals. trials to find out whether a vaccine is potentially effective. In short, the pipeline must be filled. Therefore, we must This is a route that takes a lot of time and money. We invest more in research.’ need a selection tool at an earlier stage.’

15 The quest for biomarkers

‘TBVI supports research for new vaccines and biomarkers. One of TBVI’s main objectives is to find so-called TB case protection from developing TB disease. Any surrogate We raise funds and distribute them across different biomarkers that indicate the potential success of TB endpoint must predict clinical benefit based on epidemio- research projects. Our product development team and vaccine candidates at an early stage. logic, therapeutic or clinical evidence.’ clinical development team assist and advise the researchers and developers. In the process, our partners retain A big obstacle in finding a vaccine for TB, explains TBVAC, NEWTBVAC and the combined efforts of research ownership of their inventions. Our interest is in translating Prof. Tom Ottenhoff, researcher at Leiden University Medical institutes all over Europe have yielded fifteen candidate research into product, and eventually, to have better solu- Centre (LUMC), is the period of time it takes to evaluate biomarkers that are now being further investigated. A tions for TB.’ whether a candidate vaccine is effective. ‘To determine combination of these may result in the correlates for which the efficacy of a vaccine, you have to monitor a large trial the world is searching. However, Prof. Ottenhoff expects ‘Top researchers from all over Europe are represented on group for at least several years. Besides, the group must this may take years. ‘Good validation of these biomarkers the TBVI steering committee. Together we decide on the number several 10,000s of people.’ is very important. This consists of several time consuming funding of projects. Whenever a potential conflict of interest stages, from small to larger test groups. Apart from that, is identified, for instance, when we are discussing funding To speed up research, it would be very helpful if there we need several biomarkers: to measure infection, to a project involving one or more steering committee were biomarkers to predict whether an individual is infected predict whether individuals will develop the disease, and members, these researchers are requested to leave the with TB and whether that individual will develop the symp- to measure whether individuals are protected.’ discussion. Incidentally, all decisions made to date have toms of the disease. ‘For several acute viral diseases you been by consensus. This shows that members share the can measure neutralization of protective antibodies in the The search for biomarkers may also produce new insights same priorities.’ blood of infected individuals as a measure of protection. into tuberculosis that could lead to new vaccines and better These markers are also used to determine whether a treatment. ‘When we find ‘I want to emphasize that although TBVI operates mainly in vaccinated individual will be protected. We don’t have valid biomarkers, especially Europe and is largely funded by the EU, it is not exclusively these predictive biomarkers for TB and many other chronic biomarkers that play a role European. Our vision is global and we will work together diseases.’ in the immune system, we with scientists and organizations from all over the world. will also acquire a better For example, we are now involved in a biomarker project In the case of tuberculosis, there will probably not be a understanding of the de- in which half the team members are American. Eminent single decisive biomarker. ‘TB is a very complex disease. velopment of the disease. non-European scientists such as Professor Barry Bloom, We are looking for a series of biomarkers that together That knowledge will enable a highly respected expert from Harvard Public Health make up a signature. We are searching for what we call a us to create better tools School, have also joined our Board of Trustees.’ surrogate endpoint or correlate. This is a combination of with which to combat the biomarkers that substitutes for a clinical endpoint, in this disease.’

17 5 FUNDRAISING & ADVOCACY

Opening Doors and finding sympathetic ears

Fundraising and advocacy are a primary focus of TBVI. TB hampers development To that end, TBVI has recruited Dr. Joris Vandeputte. It’s not just the human suffering that calls for increasing Traveling from one European capital to the next, he is efforts to stop TB, Dr. Vandeputte stresses. ‘Studies from always ready and willing to explain the need for fund- the World Health Organization indicate that tuberculosis ing research and development in order to find new has a huge economic impact, equaling some $ 12 billion vaccines to fight tuberculosis. annually. Countries in sub-Saharan Africa especially suffer from this. TB often affects people in their prime, people ‘Many people seem to think that tuberculosis is a disease that who should be helping to build up the economy of their humanity has successfully conquered’, says Dr. Vandeputte. country. The disease thus undermines the capacity of a ‘They associate TB with old black and white pictures of country to escape poverty.’ patients recovering in a sanatorium in Davos, or in some other location where the air is clean and healthy. However, the reality is far grimmer. In Africa and Asia, millions of ‘Wouldn’t it be great if we could people die every year as a result of TB, and millions more eliminate TB?’ are infected. Even in our affluent big European cities there are regular outbreaks of TB.’ European interest Fatal disease According to Dr. Vandeputte, Europe has an interest in One of Dr. Vandeputte’s objectives is to raise awareness fighting tuberculoses. ‘If African and Asian countries that amongst decision makers that TB is not a thing of the are seriously affected by TB can realize their economic past, but a killer that causes tremendous human suffering potential, Europe will eventually benefit from it. In the and many casualties today. He effortlessly produces data short term, combining research and development from about the disease: over 9 million new cases in 2007, an different research institutes and companies will heighten increasing number of individuals infected with multi-drug the level of knowledge and experience and improve resistant TB and extensively drug resistant TB and some scientific cooperation. Biomedical and pharmaceutical € 200 million additional funding that is needed for scientific companies must realize that they can create jobs and discovery, research and development. earn a good profit by investing in the development of new vaccines to combat TB.’

19 Much work to be done

Sowing seeds In 2000, government leaders from 189 countries de- For Dr. Vandeputte, 2008 was predominantly a year of cided to take action together to overcome the most opening doors and finding sympathetic ears. ‘Fundraising pressing global issues. They set out their targets in the takes time. It’s like sowing seeds. If the seeds fall onto Millennium Development Goals. One of the goals is to fertile soil, they will grow and blossom. With the current combat diseases like HIV/AIDS, malaria and tubercu- economic crisis, governments are less inclined to donate losis. Diseases that take a heavy toll, especially in large sums of money. That is understandable. However, poor countries. investing in new vaccines for TB is investing in the future. I’m glad to see that many organizations are aware of this. Over the last decennium, much coordinated research Several governments have already indicated that they are and development has been carried out in Europe to willing to make funds available for research. This is very find better solutions for preventing tuberculosis. To a promising. I hope that in the coming years we can reap large degree this is the result of two successive EU- what we have sown. The first large and smaller companies funded projects, TB vaccine cluster (2000-2003) and are already joining TBVI.’ TBVAC (2004-2009). TBVAC has yielded five new TB vaccine candidates, fifteen candidate biomarkers, and Making a difference three candidate adjuvant molecules were discovered With that, Dr. Vandeputte puts on his coat and leaves for and furthered in preclinical development. Four candi- the airport, on his way to another government official in dates entered or progressed through the clinical another capital to plea his case. ‘TB is a terrible disease’, phase. The projects have brought together the best he concludes. ‘If we can generate enough funding and researchers from over thirty research institutes. support research and development, we can really make a difference. Wouldn’t it be great if we could eliminate TB? However, much work remains to be done. In addition, I think it can be done. That’s what keeps me going.’ a great deal of funding is needed. The STOP-TB partner- ship estimated a global requirement of $ 1.5 billion for 2006-2015. Funding sorely needed for research and Tuberculosis has a huge development of TB vaccines and biomarkers and for increasing the capacity of existing clinical trial sites in economic impact, equaling developing countries. some $ 12 billion yearly 21 TBVI IN ACTION

Bridging the gap

One of the main features of TBVAC in recent years was asked to join TBVI’s PDT. A team consists of four and TBVI now and in the future, is support from the experts, explains Dr. Thiry. Its aim is to ensure the transition product development team or PDT. The PDT is a team from research to development. ‘This transition often requires of international experts in vaccine research and devel- a change of mindset. Academic researchers are focused opment. The experts assist researchers in bridging the on discovery. They have to be creative. Developers, on the gap between scientific discovery and development. other hand, have to be far more goal and product-oriented. They cooperate closely with partners with the shared We help researchers focus more on the result we’re aim- goal of bringing products to clinical development. ing for’. Responsibility for, and ownership of the candidate vaccine remains with individual project partners. The PDT holds regular meetings with the researchers. ‘It is a very light and effective structure. We are well targeted Recently, TBVI installed a clinical development team to and we work very closely with our partners. We meet at support the product development team. Although they least once annually to review progress, to advise and to work closely together, each team has its own specific role bring in expertise that is lacking. Partners value our con- to play in the development process. The product develop- tribution. We possess a supportive attitude; we are there ment team supports researchers in getting their product to assist, not to check up on partners.’ The PDT lays down from discovery to the preclinical phase. From there, the their findings in a report for the TBVI Steering Committee. On clinical development teams take over to bring the vaccine the basis of this information, the Steering Committee de- candidate further towards clinical evaluation. cides on funding for the subsequent stages of development.

Ensuring the transition Reducing waste of time and resources Dr. Georges Thiry is head of the PDT. He works in France Fortunately, more candidate vaccines are entering the at PATH, a non-governmental organization focusing on clinical stage. This stage of development has its own finding solutions for emerging and epidemic diseases and peculiarities. Therefore, TBVI has also brought into existence improving the health situation in poorer countries especial- a clinical development team (CDT), lead by Prof. Juhani ly. In the past, he has worked for several commercial or- Eskola. Prof. Eskola is Deputy Director General of the ganizations, such as GlaxoSmithKline, a leading interna- National Public Health Institute KTL in Finland. He has tional pharmaceutical company. His expertise in project extensive experience in vaccine development, both in the management and planning was one of the reasons he academic research institute and in private industry.

23 Making tremendous progress

From 2000 to 2004, he was the Senior Vice President of candidates are promising or not. If they are, we have to One of the researchers who has benefited from Aventis Pasteur in France. Like Dr. Thiry, he combines move forward. If they are not, we’re wasting valuable time the expertise of the product development team is Prof. academic expertise with management experience. and resources.’ Carlos Martin. He is the coordinator of basic research for live vaccines at Zaragoza University, Spain. Over ‘Our main purpose is to support academic researchers in Finding better vaccines the past ten years, he and his fellow researchers have taking their product through clinical phase I to early phase Dr. Thiry and Prof. Eskola are united in the quest for better discovered a promising candidate vaccine that is now II’, says Prof. Eskola. ‘We work closely with the PDT, since vaccines to reduce the number of TB victims. Says Prof. on the verge of preclinical testing. decisions in product development have an impact on clinical Eskola, ‘I’m convinced that new TB vaccines are sorely strategy and vice versa. Therefore we often hold joint needed. Millions of people die from tuberculosis each ‘Over the last four years, assistance from the product meetings.’ The CDT is also ready to share its views with year. My education and background is in pediatric infec- development team has been essential in getting us to smaller companies. ‘Big industry has its own expertise, tious disease. I know of no other field in which I could the point we’re at now’, says Prof. Martin. ‘We are they don’t need us so much.’ better utilize my skills and influence.’ good at basic research, but we have no experience in development. The PDT advised us on which steps to Prof. Eskola emphasizes that the clinical development ‘I hope TBVI is able to generate more funding for more take. Contact with industry was completely new to me. team is very goal-oriented. ‘Academic researchers pose projects and raise awareness of the need for increased The PDT persuaded us to hire a project manager who, all kinds of scientifically significant questions. Our pur- investment to overcome TB ’, says Dr. Thiry. ‘In recent years, in conjunction with the PDT, takes care of all organiza- pose is to direct their attention to the questions that carry TBVAC has drawn together a consortium of over thirty tional aspects and paperwork. the product forward. Most scientists are not particularly groups that share the same objective, working together experienced in registration and licensing, but these pro- while maintaining their individual remit and expertise. ‘Thanks to the PDT, we have made tremendous prog- cesses are essential in vaccine development. You have to Maintaining this network is in itself a remarkable achieve- ress. A local company in Spain will produce the vaccine ask the right questions. If the right questions yield the right ment. It very much increases the chances of finding a according to good manufacturing practice. We are answers, then you go on. If they yield the wrong answers, solution to TB.’ close to conducting preclinical trials. In the coming you terminate the project.’ years, we hope to undertake further tests and clinical trials. It’s very difficult to get all the necessary authori- Scientists may feel the TBVI development teams limit ‘The transition from research zation. The main problem with live vaccines is safety their academic freedom, admits Prof. Eskola. ‘And they of their use in humans. We have applied for extra are right’, he says laughing. ‘But our goal is to bring new to development often requires funding with NEWTBVAC. Our project manager pre- TB vaccines to the market. In the short term, we help re- pared the application in cooperation with the product searchers get answers to the issue of whether vaccine a change of mindset’ development team.’

25 ORGANIZATION

Steering Committee

Prof. Paul-Henri Lambert, Chairman Dr. Germain Puzo Director International Advanced Course of Vaccinology, Director of Research at the National Center for Scientific University of Geneva, Geneva Research (CNRS), Head of the research team “Immunochemistry and Mycobacteria Glycoconjuguates”, Prof. Peter Andersen, DVM, DMSc Toulouse Director, Infectious Disease Immunology, Vice President, Vaccine R&D, Statens Serum Institut, Copenhagen Dr. Ann Rawkins TB project co-ordinator, HPA, Centre for Emergency Prof. Hazel M. Dockrell Preparedness and Response, Porton Down Deputy Director (Research) and Professor of Immunology, London School of Hygiene and Tropical Medicine, Dr. Helen McShane London Wellcome Senior Clinical Research Fellow, University of Oxford, Oxford Prof. Brigitte Gicquel Head of the Mycobacterial Genetics Unit, Institute Pasteur, Dr. François Spertini Paris Prof. associé, Médecin-chef, Service d’Immunologie et d’Allergie, Centre Hospitalier Universitaire Vaudois, Prof. Dr. Dr. h.c. Stefan H.E Kaufmann Lausanne Director, Max-Planck-Institute for Infection Biology Department of Immunology, Berlin Prof. Douglas B. Young Fleming Professor of Medical Microbiology, Imperial Col- Prof. Carlos Martin lege London and Head of Division of Mycobacterial Re- Microbiology Professor, University of Zaragoza, Zaragoza search, National Institute for Medical Research, London

Prof. Tom H.M. Ottenhoff, MD, PhD Professor in Immunology, Head group Immunology and Immunogenetics of Bacterial Infectious Diseases, Leiden University Medical Center, Leiden

27 Governance Board Board of Trustees

Dr. Martin C.Th. Scholten, Chairman Dr. Kalevi Reijonen, Mr. John Bowis General Director, Animal Sciences Group President and CEO, FIT BIOTECH, Tampere Former Member of European Parliament, Former Minis- Wageningen UR ter of Health and Transport of the UK, London Dr. Jan Gheuens, Drs. Dick J. Pouwels, RC Senior Program Officer Tuberculosis, Bill and Melinda Mr. Jacques-François Martin Managing Director, Animal Sciences Group Gates Foundation, Seattle Chairman and CEO, Parteurop, Former President of The Wageningen UR Vaccine Fund, Lyon Prof. Barry R. Bloom Prof. P.H. Lambert, Professor and Joan L. and Julius H. Jacobson Professor of Prof. Charles Mgone Director International Advanced Course of Vaccinology, Public Health, Harvard School of Public Health, Boston Executive Director, EDCTP, The Hague University of Geneva, Geneva Chair Steering Committee Prof. Peter Piot Prof. Hans Wigzell Director Institute for Global Health, Imperial College, Professor and Deputy Chairman, Karolinska Institute, Chair, Board of Trusties - To be appointed London Stockholm

Dr. Dorette Corbey Former Member of European Parliament, Haarlem

29 Operational Office TBVI Entity

Dr. Jelle Thole Dr. Georges Thiry Director Consultant and Chair product development team ▪ Verify coverage of financial resources Dr. Joris Vandeputte Dr. Micha Roumiantzeff for projects proposed by SC Verify process of decisions by SC, Sr Vice President Advocacy and Fundraising Consultant product development team ▪ BoT and OO ▪ Approval annual report Erna Balk-Spruit Dr. Eddy Rommel ▪ Appoint members of OO, SC members Director Communications and Advocacy Relations Consultant product development team and members of BoT

Babs Verblackt Dr. Barry Walker Governance Board Associate Communications and Advocacy Relations Consultant product development team

Anne Meinema Prof. Paul-Henri Lambert Financial Officer Consultant product development team Board of Trustees Steering Committee

Koen de Lange Prof. Juhani Eskola ▪ Strategic advice ▪ Strategic plan Legal Officer Consultant and Chair clinical development team ▪ Overall budget approval ▪ Resource mobilization ▪ Project/decisions ▪ Coordination with other Bieneke Baas Dr. Roland Dobbelaer initiatives HRM Advisor Consultant clinical development team Operational Office ▪ Connect with industry

Cora Agterdenbosch Dr. François Spertini ▪ Project initiation, submission and management Management Assistant Consultant clinical development team ▪ Assist SC, GB and BoT ▪ Coordinating and connecting ▪ Resource mobilization ▪ PDTs

31 PARTNERS

Argentinia Veterinary Institute of Wageningen UR, BioMedical Research of Veterinary and Agriculture Research Centre, National Institute Wageningen UR, Netherlands Vaccine Institute, European for Agricultural Technology. Developing Countries Clinical Trials Partnership. Belgium Senegal Université Libre de Bruxelles, Institut Scientifique de Sante Hospital Le Dantec. Publique, GSK-Biologicals, European Commission. Spain Denmark Universidad de Zaragoza Facultad de Medicina, Fundacio Statens Serum Institute, European Malaria Vaccine Initiative (EMVI). Institut De Investigado de Ciencies De La Salut Germans Trias I Ethiopia Pujol, CZ Veterinaria. Armauer Hansen Research Institute. Switzerland Finland Institute for Research in Biomedicine, University of Geneva; FIT Biotech. University Hospital of Basel, University of Zürich, Centre Hospi- France tal Universite de Vaudois, STOP TB Partnership. Centre National de la Recherche Scientifique, Institute National South Africa de la Santé et de la Recherche Médicale, Institute Pasteur University of Cape Town. Paris, Institute Pasteur Lille, PX’ therapeutics. South Korea The Gambia Institut Pasteur Korea, Educational Foundation Yonsei Univer- MRC The Gambia. sity, International Vaccine institute. Germany United Kingdom University of Lübeck, Technical University of Munich; Max- University of Birmingham, Aston University, Manchester Uni- Planck Institute for Infection Biology; University of Tübingen, versity Medical School, Imperial College of Science Technol- University of Ulm, University of Erlangen-Nürnberg, Vakzine ogy and Medicine, National Institute for Biological Standards, Projekt Management. University of Oxford, London School of Hygiene and Tropical Italy Medicine, Health Protection Agency Porton Down, Veterinary National Institute for Infectious Diseases “Lazzaro Spallanzani”; Laboratory Agencies, University College London. University of Palermo, Instituto Superiore Di Sanita, University USA of Padua. Aeras Global TB vaccine Foundation, Bill and Melinda Gates Netherlands Foundation. Centre, Wageningen University and Research Centre, Central

33 DONORS

35 FINANCIAL REPORT

Statement of activities

Revenue EC 215,330 100% Total 215,330

Expenses Vaccine Research Program 197,632 92% Support Services 17,698 8% Total 215,330

Net Assets Beginning of year 0 8% End of year 0

The financial statements 2008 have been audited by PriceWaterhouseCoopers accountants NV. In their auditors’ report dated 24 June 2009 they 92% expressed an unqualified opinion on these financial statements. The financial report as stated above has been derived from the financial statements 2008.

37 Publication: TuBerculosis Vaccine Initiative (TBVI), Lelystad The Netherlands

Text: Jos Leijen, Bureau Schrijfwerk, Voorhout

Graphic Design: Chantal de Jonge, Mooi Paars, Vlaardingen