Doing our part: Innovating to fight Neglected Tropical Diseases April 2017
Designed by ACW, London www.acw.uk.com
Contents
BIOPHARMACEUTICAL INDUSTRY CONTRIBUTIONS TO THE GLOBAL FIGHT AGAINST NTDs
4 8
Staying the Course: A Global Commitment to Fight NTDs - The scope of the NTD epidemic - The London Declaration
16 18
Scaling Up Access to Existing Treatments
Strengthening Health Systems
Boosting Innovation - Discovery - Pipeline - Funding
R&D PIPELINE FOR NTDs
20 22 24 26 28 30
American trypanosomiasis (Chagas disease)
Chikungunya
Dengue (dengue hemorrhagic fever)
Human African trypanosomiasis (sleeping sickness)
Leishmaniasis
Lymphatic filariasis
32 34 36 38 40 42
Mycetoma (river blindness)
Onchocerciasis (river blindness)
Rabies
Schistosomiasis
Trachoma
Abbreviations
STAYING THE COURSE: A GLOBAL COMMITMENT TO FIGHT NTDs We are witnessing one of the greatest public health achievements of the century. This year marks the 5th anniversary of the World Health Organization’s (WHO) Neglected Tropical Diseases (NTD) Roadmap1, establishing targets and milestones for the control and elimination of ten of the most prevalent NTDs by 2020. Inspired by the WHO NTD Roadmap, a group of 20 partners from governments, intergovernmental organizations, NGOs, foundations and R&D biopharmaceutical companies came together to pledge support to the WHO by signing the London Declaration2. Today, the London Declaration’s endorsers have grown to include over 200 organizations3.
“Today, we have joined together to increase the impact of our investments and build on the tremendous progress made to date. This innovative approach must serve as a model for solving other global development challenges and will help millions of people build self-sufficiency and overcome the need for aid.” Bill Gates, co-chair of the Bill & Melinda Gates Foundation, at the signing of the London Declaration in 2012 Now at the halfway mark of the WHO NTD Roadmap’s timeline, this publication outlines how the R&D biopharmaceutical industry is contributing to this global agenda, with active research projects to uncover new or improved treatments and vaccines. It also provides context of how these R&D efforts are part of an integrated approach to combatting NTDs, including an unprecedented medicines donation program of 14 billion treatments over ten years and support for local capacity building.
THE SCOPE OF THE NTD EPIDEMIC Although most NTDs are preventable and treatable, they sadly continue to be a heavy burden on the most vulnerable, disadvantaged people in the world. One person in seven suffers from one or more NTDs – comparable to the entire population of Europe – with the vast majority of cases in low- and middleincome countries (LMICs). NTDs are caused by a range of different parasites, bacteria and viruses, which primarily thrive in subtropical climates. They can be painful, blinding and disfiguring; each year they lead to the poor-health, disability and death of hundreds of thousands of people. As they are often chronic and disabling, NTDs have enormous educational and economic impacts, keeping children out of school and adults out of work. At the start of this millennium, it was estimated that in India alone, an average of USD 1 billion was lost to lymphatic filariasis each year due to healthcare costs and loss of productivity. Research has shown that school children infected with intestinal worms had a 20% lower probability of school enrolment and, subsequently, a 40% reduction in income as an adult4. The landscape of neglected disease control is continuously changing. Climate change is driving diseases beyond their traditional geographies, resulting in outbreaks of dengue and Chagas disease beyond the tropics. Furthermore, complex changes in demography, such as urbanization and globalization, impact upon the spread of disease, as illustrated by the recent outbreaks of Chikungunya, Ebola and Zika virus. NTDs mire communities in a cycle of poverty, and hinder progress towards the sustainable development agenda. The increased commitments from national governments and their partners to achieve the targets of the WHO NTD Roadmap means significant improvements to the health, wealth and quality of life of over 1 billion people worldwide.
4
THE LONDON DECL AR ATION The London Declaration represented a turning point in global efforts to control and eliminate the most common NTDs. The R&D biopharmaceutical industry remains a committed partner in this agenda IFPMA signatories to the London Declaration are AbbVie, Bayer, Bristol-Myers Squibb, Eisai, GlaxoSmithKline, Johnson & Johnson, Merck, MSD, Novartis, Pfizer and Sanofi.
COMMITMENTS OF THE LONDON DECL ARATION ON NTDs Sustain, expand and extend programs that ensure the necessary supply of drugs and other interventions to help eradicate some diseases and to help control others by 2020.
Advance R&D through partnerships and provision of funding to find next-generation treatments and interventions for neglected diseases.
Enhance collaboration and coordination on NTDs at national and international levels through public and private multilateral organizations.
Enable adequate funding with endemic countries to implement NTD programs necessary to achieve these goals, supported by strong and committed health systems at the national level.
Provide technical support, tools and resources to support NTD-endemic countries to evaluate and monitor programs.
AT THE HALFWAY MARK, THE WORLD IS ON TRACK TO DELIVERING ON PROMISES OF THE LONDON DECL ARATION 5 • In 2015, biopharmaceutical companies donated an estimated 2.4 billion tablets, enough for 1.5 billion treatments to prevent and treat NTDs – an increase of 11.7% from 2014. • Between 2012 and 2014, the number of people who needed treatment decreased by 230 million. • Since the London Declaration, there have been over 7.9 billion tablets in pharma donations, which is enough for 5 billion treatments. • 87% of countries in Africa have been fully mapped for the London Declaration’s targeted NTDs.
1 http://www.who.int/neglected_diseases/NTD_RoadMap_2012_Fullversion.pdf 2 h ttp://unitingtocombatntds.org/sites/default/files/resource_file/london_ declaration_on_ntds.pdf 3 http://unitingtocombatntds.org/endorsements 4 h ttp://www.globalnetwork.org/sites/default/files/Social%20and%20 Economic%20Impact%20Review%20on%20Neglected%20Tropical%20 Diseases%20Hudson%20Institute%20and%20Sabin%20Institute%20 November%202012_1.pdf 5 http://unitingtocombatntds.org/report/fourth-report-reaching-unreached
5
DOING OUR PART: COMPREHENSIVE EFFORTS TO FIGHT NTDs
Scaling up access to existing treatments Donation of 14 billion treatments over 10 years to help eliminate or control 10 NTDs
Strengthening health systems
Boosting innovation
Over 40 health partnerships to build capacity to fight NTDs where they are endemic
109 active R&D projects to develop the next generation of medicines and vaccines for NTDs
NTDs require a multi-stakeholder approach to drive further research tailored to developing needs, improve health policies and access to treatments, and boost healthcare system capacity. That is why the R&D biopharmaceutical industry combats NTDs in an integrated manner. 6
7
1
BOOSTING INNOVATION
DISCOV ERY
There has been considerable progress in new technologies, including medicines, vaccines, diagnostics and pesticides, to combat NTDs. Since the launch of the London Declaration in 2012, a number of new product approvals helped better address NTD challenges.
DENGUE (2015) Dengue is a threat to nearly half of the world’s population, yet until recently there was no specific treatment or vaccine available to reduce the burden of this disease. Dengue is the fastest progressing vector-borne disease and can cause massive outbreaks with a disruptive effect on healthcare systems. Mostly asymptomatic, dengue can also lead to hospitalization, serious illness and death among people leaving in endemic areas in Asia Latin America and Africa. The newly approved dengue vaccine6 presents a major advance towards the achievement of WHO objectives to reducing dengue mortality and morbidity by at least 50% and 25% respectively, by 2020. Additional dengue vaccine candidates are in development.
6 Dengvaxia® (CYD-TDV), developed by Sanofi Pasteur. 7 VERMOX™ chewable (mebendazole chewable 500 mg tablets), developed by Janssen Pharmaceuticals, Inc. 8 Eisai Co., Ltd. received prequalification from the WHO for diethylcarbamazine citrate (DEC) 100 mg tablets in 2013.
8
SOIL-TR ANSMIT TED HELMINTHIA SES (2016)
LYMPHATIC FIL ARIA SIS (2013)
Soil-transmitted helminthiases, otherwise known as intestinal worms, are a chronic and debilitating illness with particular impact on children, stunting growth, impairing cognitive development and keeping children out of school.
Lymphatic filariasis is often referred to as elephantiasis, due to severe disfigurement, disability, and swelling from fluid build-up caused by improper functioning of the lymphatic system. Infection occurs when filarial parasites are transmitted to humans through mosquitoes. An estimated 120 million people worldwide live with the disease.
The approval of a chewable formulation of mebendezole7 supports global efforts to reduce the burden of parasitic infections in young children. Donations of this treatment are planned to be rolled out towards the WHO’s objective to provide treatment to over 75% of 870 million at-risk children.
The development and distribution of diethylcarbamazine citrate (DEC)8 through large-scale mass drug administration supports the WHO target of eliminating the disease by 2020.
109
7 7 COMPOUNDS FOR NTDs CURRENTLY UNDERGO L ATE STAGE TESTING
109 ACTIVE R&D PROJECTS FOR NTDs
To ensure that new generations of improved treatments and interventions are discovered, despite low commercial incentives in the area of NTDs, the biopharmaceutical industry engages in a variety of multi-sectoral research models. The most common model sees NTD R&D through partnerships. This innovative approach has proven to enable the sharing of expertise and acceleration of research, reduced risks and duplications, and sustainable financing.
90
%
OVER 90% OF THE ACTIVE R&D PROJECTS FOR NTDs ARE COLL ABOR ATIVE EFFORTS
50 OVER 50 PARTNERS ( UNIVERSITIES, NGOs, PUBLIC AND PRIVATE SECTOR INSTITUTES )
Today, the industry’s NTD research efforts are done in partnership with over 50 organizations, including renowned universities, non-governmental organizations and public and private sector institutes. Biopharmaceutical R&D can be a lengthy process, with instances of life-changing discovery amidst years of hypotheses, setback and recalibrations. As the science becomes more complex, research becomes more challenging. As well as responding to emerging trends such as globalization and climate change, local needs also demand innovation in the space of pediatric formulations and medicines and vaccines that can be distributed outside of the cold chain. Research partnerships help streamline global efforts, identify remaining R&D gaps and preventing the duplication of efforts. Adding to their R&D efforts and donations, companies provide in-kind contributions that are specifically targeted to NTDs R&D. This includes sharing intellectual property assets such as compounds and compounds libraries for research purposes, giving access to research facilities, hosting scientists, and providing training. It also includes transfer of technology, and building technical expertise to develop, manufacture, register and distribute NTDs products. 9
THE R&D PROCESS RESEARCH Practical Testing
Critical Trials
Regulatory Review
Scale-up to Manufacturing
Post-Marketing Surveillance
4-6 YEARS
1 YEAR
PHASE IV
5
PHASE I PHASE II PHASE III
6-7 YEARS
NEW DRUG APPLICATION SUBMITTED
Target identification (TI) Lead generation (LG) Lead identification (LI) Lead optimization (LO)
250
PATENT APPLICATIONS FILED
BASIC RESEARCH & DRUG DISCOVERY
5,000 - 10,000 COMPOUNDS
INVESTIGATIONAL DRUG APPLICATION SUBMITTED
PHASE 0
Early Phase Research
DEVELOPMENT
ONE MARKETED MEDICINE
0.5-2 YEARS
CONTINUOUS
PIPELINE IFPMA companies are involved in 109 active R&D projects for NTDs. Nearing the end of what is on average a 10-15 year R&D process, IFPMA member companies and their partners are approaching imminent NTDs breakthroughs, with late stage testing (Phase III) of treatments and vaccines of 7 compounds, within the disease areas of American Trypanosomiasis (Chagas disease), dengue, Human African trypanosomiasis (sleeping sickness), lymphatic filariasis, rabies, and trachoma. In most cases, research undertaken in partnerships is conducted on a not-for‑profit basis, with effective mechanisms to ensure access to treatments in endemic countries. As stated by the 2016 Access to Medicines Index, there are access plans in place for most high-priority pipeline products9.
“Overall, 56% of 151 high-priority, low-incentive products in R&D have access plans in place. As expected, there are more products with access plans toward the end of the pipeline; there is a marked increase as projects move into clinical development, and then again between clinical phases II and III. The majority (72%) of latestage projects have access plans in place.” Access to Medicines Index 2016 9 https://accesstomedicineindex.org/
10
As more projects progress into later stages of clinical development, continued support in the space of capacity building will be key to ensure that clinical trials and regulatory infrastructures in low- and middle-income countries are capable getting new medicines and vaccines to the people that need them. The final section of this publication provides the most up-to-date record of active research and development for the next generation of medicines and vaccines for the following NTDs: American trypanosomiasis (Chagas disease), Chikungunya, dengue, Human African trypanosomiasis (sleeping sickness), leishmaniasis, lymphatic filariasis, mycetoma, onchocerciasis (river blindness), rabies, schistosomiasis, and trachoma.
R&D PIPELINE BY INDUSTRY AND PARTNER S FOR NTDs Schistosomiasis Rabies
Current projects: 5 Medicines: 5
Trachoma Current projects: 1 Medicines: 1
Current projects: 1 Vaccines: 1 Onchocerciasis (river blindness)
American trypanosomiasis (Chagas disease) Current projects: 28 Medicines: 26 Vaccines: 2
Current projects: 15 Medicines: 15
Mycetoma Current projects: 1 Medicines: 1 Chikungunya Current projects: 4 Medicines: 3 Vaccines: 1
Lymphatic filariasis Current projects: 12 Medicines: 12
Dengue (dengue hemorrhagic fever) Current projects: 12 Medicines: 5 Vaccines: 7 Leishmaniasis Current projects: 21 Medicines: 21
Human African trypanosomiasis (sleeping sickness) Current projects: 9 Medicines: 9
IFPMA companies are involved in 109 active R&D projects for NTDs
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FUNDING Eliminating NTDs requires sustained funding for research and development of new treatments and vaccines. According to the latest G-FINDER report from Policy Cures Research, which measures global investment into R&D of new products for 39 neglected diseases (including malaria, tuberculosis, and HIV/ AIDs10), USD 3.04 billion was made available for neglected disease research in 2015, as well as an additional USD 631 million invested in Ebola and other African viral hemorrhagic fever (VHF) research.
“2015 was the fourth year in a row that industry has increased its investment in neglected disease R&D – the only sector to have recorded year-on-year growth for such a stretch.” Policy Cures Research, G-FINDER 2016 • Industry investment in neglected disease R&D in 2015 was the highest ever recorded in the G-FINDER survey. • In 2015 the pharmaceutical industry contributed USD 471 million to funding for neglected disease research.
10 Full list of diseases on page 11 of the G-FIN D ER report.
12
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DEDIC ATED INTERNATIONAL INITIATIV ES FOR NTD RESE ARCH
GLOBAL HE ALTH INNOVATIV E TECHNOLOGY FUND (GHIT ), FACILITATING INTERNATIONAL R&D The first of its kind in Japan, the GHIT Fund is a public-private partnership between the Japanese government, multiple pharmaceutical companies, the Bill & Melinda Gates Foundation, the Wellcome Trust, and United Nations Development Programme (UNDP). GHIT Fund invests and manages a portfolio of development partnerships aimed at neglected diseases that afflict the world’s poorest people. GHIT Fund mobilizes Japanese and international pharmaceutical companies and academic and research organizations to engage in the effort to get new medicines, vaccines, and diagnostic tools to people who need them most. IFPMA member companies involved in GHIT are: Astellas, Chugai, Eisai, Daiichi Sankyo, Merck, Otsuka, Shionogi, and Takeda. For more information please visit www.ghitfund.org
WIPO RE:SE ARCH, A COLL ABORATIVE PL ATFORM TO BOOST R&D WIPO Re:Search was established in October 2011 by the World Intellectual Property Organization (WIPO) in collaboration with BIO Ventures for Global Health (BVGH) and with the active participation of leading pharmaceutical companies. The consortium now consists of over 100 organizations from both the private and public sectors, including non-profit organizations and academic research institutes. WIPO Re:Search member organizations share their intellectual property assets such as compounds and compound libraries, technologies, expertise, samples, and data to bridge research gaps, reduce costs of product development, and advance drug, vaccine, and diagnostic research and development for NTDs, malaria, and tuberculosis. To date BVGH has established 105 research collaborations through WIPO Re:Search. Collaborations cover a range of areas that include the sharing of data and services (such as access to company research facilities, screening of compounds, hosting of scientists) as well as other forms of expertise. IFPMA member companies involved in WIPO Re:Search are: Eisai, GlaxoSmithKline, Janssen (Johnson & Johnson), Merck, MSD, Novartis, Pfizer, Sanofi, and Takeda11.
THE EUROPE AN & DE V ELOPING COUNTRIES CLINIC AL TRIAL S PARTNER SHIP ( EDC TP ) & THE SPECIAL PROGR AMME FOR RESE ARCH AND TR AINING IN TROPIC AL DISE A SES ( WHO/TDR ), SUPPORTING RESEARCHERS AND CLINIC AL TRIAL RESEARCH TEAMS FROM LOW- AND MIDDLE- INCOME COUNTRIES ( LMICs) EDCTP and WHO/TDR offer a Clinical Research and Development Fellowship. The overall objective is to strengthen collaboration between research institutions, researchers and clinical staff in LMICs, pharmaceutical companies, and Product Development Partnerships (PDPs)12. By working together, they ensure harmonization and synergy through a Joint Call for Proposals. The host organizations, pharmaceutical companies and PDPs train scientists, for a period of up to 24 months to develop specialist product development skills not readily taught in academic centers or public research institutions. The fellows are expected to become an important resource for institutional capacity development, to undertake and manage clinical research in accordance with international regulatory requirements and standards13. The fellowship has increased the number of individuals trained and helped facilitate common communication with researchers and clinical staff, pharmaceutical companies, PDPs and research institutions. IFPMA member companies involved in training fellows for the year 2015/2016 are: Astellas, Bayer, GlaxoSmithKline, Janssen (Johnson & Johnson), Merck, Novartis, and Sanofi. For more information please visit EDTCP: www.edctp.org/call/edctp-tdr-clinical-research-development-fellowships-2/
For more information please visit
TDR: www.who.int/tdr/capacity/strengthening/career_development/en/
WIPO: www.wipo.int/research/en/
Dedicated centers for NTD research
11 http://www.wipo.int/research/en/ 12 http://www.edctp.org/web/app/uploads/2016/07/EDCTP2-Workplan-2016.pdf 13 http://www.edctp.org/call/edctp-tdr-clinical-research-development-fellowships-2/
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PHARMACEUTIC AL INDUSTRY CENTER S DEDIC ATED TO NTDs R&D COMPANY
R&D CENTER
LOCATION
SINCE
AbbVie
AbbVie
North Chicago, IL
2009
Cambridge Biomedical Campus (CBC)
Cambridge, UK
2015
Alderley Park*
Macclesfield, UK
1999
Celgene
Celgene Global Health
Summit, NJ, USA
2009
GlaxoSmithKline
Diseases of the Developing World center
Tres Cantos, Spain
2002
Merck
R&D Translational Innovation Platform “Global Health”
Geneva, Switzerland
2014
MSD (operated as Merck & Co., Inc. in the USA and Canada)
MSD Wellcome Trust Hilleman Laboratories
New Delhi, India
2009
Novartis Institute for Tropical Diseases (NITD)
Singapore**
2002
Novartis Institutes for BioMedical Research (NIBR)
Emeryville, CA, USA
2016
Genomics Institute of the Novartis Research Foundation (GNF)
La Jolla, USA
2010
Eisai Inc. Andover Research Institute
Andover, MA, USA
1987
Eisai Pharmaceuticals India Pvt. Ltd.
Visakhapatnam, India
2007
Tsukuba Research Laboratories (Ibaraki Prefecture)
Japan
1982
Marcy l’Etoile Research & development Campus
Lyon, France
Vaccines (dengue) since the 90s Medicines since 2015
AstraZeneca
Novartis
Eisai
Sanofi
The biopharmaceutical industry’s efforts are supported by R&D centers which are dedicated solely to diseases that disproportionately affect people in low- and middle-income countries. Some companies integrate these R&D activities within their broader R&D organization while others provide financial and technical support to independent organizations. * T he facility is planned to cease its operations in late 2016/early 2017; currently ongoing projects are those involving AWOL, malaria and tuberculosis. ** In October 2016, Novartis has announced that NITD will move its operations to Emeryville, California, where it will be co-located with the Infectious Disease Research team.
15
2
SCALING UP ACCESS TO EXISTING TREATMENTS As we search for the next generation of treatments and vaccines, we need to continue to utilize to their full power the existing cost-effective and high-impact treatments for NTDs. The R&D biopharmaceutical industry is to delivering on its London Declaration pledge of 14 billion treatments through 2020 to address the 10 diseases responsible for more than 90% of the global neglected disease burden. In 2015 alone, biopharmaceutical companies donated an estimated 1.5 billion treatments to prevent and treat neglected tropical diseases – an increase of 11.7% from 2014 and reaching 850 million people worldwide14. By 2020, nearly USD 18 billion worth of medicines will have been distributed, the largest medicine donation the world has ever seen.
By 2020, nearly USD 18 billion worth of medicines will have been distributed, the largest medicine donation the world has ever seen.
Five of the 10 NTDs covered in the London Declaration can be controlled through what is known as mass drug administration (MDA) – large-scale population treatment with safe and effective medicines to all people living in high-risk areas. These diseases include: lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (hookworm, roundworm, and whipworm), and trachoma.
The success of these drug distribution campaigns relies on an integrated treatment approach. In the past, many countries used to conduct separate treatment campaigns for individual diseases. Now, many programs provide treatments for several diseases at the same time. For example, a national program can treat all children in a region for intestinal worms, onchocerciasis and lymphatic filariasis in a single school visit. This provides immediate relief to any children that happen to carry the parasites, while at the same time halting the spread of these diseases within a community. After a few years of systematic mass drug administrations, a disease can be eradicated from a country, and even eliminated entirely across the world. Additionally, these large-scale campaigns offer a fantastic opportunity to reach people with other health interventions. Partners are also looking at ways to use these community distribution platforms in a more coordinated way with other health programs. The other five NTDs can be controlled by what is known as innovative and intensified disease management (IDM) – individual diagnosis, treatment and rehabilitation of people that have been infected. These include Chagas disease, Guinea worm disease, Human African trypanosomiasis (sleeping sickness), leprosy and visceral leishmaniasis. 14 http://unitingtocombatntds.org/impact.
16
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3
STRENGTHENING HEALTH SYSTEMS
NTDs control and elimination is a challenging task with a need for a variety of locally-tailored solutions. Adding to their research and development efforts and donations, IFPMA member companies are also involved in over 40 partnerships to assist countries to bolster the capacity of their health workforce and medical infrastructures to meet the needs of people with NTDs. Political commitment and leadership from national programs are paramount. All projects involve collaboration with national governments and community-based platforms.
Political commitment and leadership from national programs are paramount. All projects involve collaboration with national governments and community-based platforms.
Programs focus on building health services that are accessible and staffed with qualified healthcare workers to enable the delivery of medicines and vaccines down the last mile. They also provide people living in endemic areas information to help prevent the spread of infection, and infrastructure programmes to address water, sanitation and hygiene. So that every effort is made to support the WHO and national governments in meetings targets of the NTD Roadmap, the R&D biopharmaceutical industry is committed to finding new ways to address gaps, share best practices and advance solutions.
These partnerships include supporting local NGOs in establishing campaigns around identifying the symptoms of dengue, supporting public health institutes in development of clinical guidelines on treatment of leprosy, and supporting governments in setting up mobile intervention teams that can rapidly respond to outbreaks of Human African trypanosomiasis.
For more information about these programs, and to learn of many other initiatives, please visit the IFPMA Health Partnerships Directory (www.partnerships.ifpma.org), the most comprehensive international database for health development programs involving the R&D biopharmaceutical industry. Each partnership profile offers valuable insights into why a specific program was developed, and the ways in which it is helping to make a difference to communities around the world. 18
19
AMERICAN TRYPANOSOMIASIS Chagas disease DISE A SE IMPAC T 15,16 American trypanosomiasis is caused by the kinetoplastid protozoan parasite Trypanosoma cruzi, which is primarily transmitted by a triatomine bug – an insect vector. The vector-borne transmission occurs primarily in the Americas. Other ways of transmission are blood transfusion, organ transplantation, congenital and oral transmissions. The disease has two clinical stages: acute and chronic. Acute is characterized by fever, malaise, facial oedema, generalized lymphadenopathy, and hepatosplenomegaly. Chronic asymptomatic disease shows no signs of the disease, yet the parasite remains transmittable to others. Chronic symptomatic disease develops in 10% to 30% of infected patients. Trypanosoma cruzi infection is curable if treatment is initiated soon after infection. In the chronic phase antiparasitic treatment can also prevent or curb disease progression.
KE Y FAC TS17, 18 • A n estimated 6 million to 7 million people are infected worldwide, with the disease being endemic, but not limited to 21 countries across Latin America. •5 % of children die with the acute stage of the disease, while chronic asymptomatic disease can last 10 years to lifetime. • Up to 30% of chronically infected people develop cardiac alterations and up to 10% develop digestive, neurological or mixed alterations, which may require specific treatment. • Vector control is the most useful method to prevent Chagas disease in Latin America.
15 http://www.dndi.org/diseases-projects/chagas/ 16 http://www.who.int/mediacentre/factsheets/fs340/en/
20
17 http://www.dndi.org/diseases-projects/chagas/ 18 http://www.who.int/mediacentre/factsheets/fs340/en/
CURRENT R&D PROJEC TS COMPA COMPAN NYY
PA PARTNER RTNERSS
PROJECTT PROJEC
PHAASE SE PH
PE TTYYPE
AbbVie AbbVie
DNDi DNDi
Compoundscreening, screening,preclinical preclinicalsupport, support, Compound technicalconsulting consulting technical
Leadidentification identification Lead
Medicine Medicine
Astellas Astellas
AIST AIST
Discovery Discoveryof ofanti-protozoan anti-protozoanparasite parasitedrugs drugsfor for Trypanosoma Trypanosomacruzi cruzi
Discovery Discovery
Medicine Medicine
AstraZeneca AstraZeneca
DNDi DNDi
Focused Focusedcompound compoundlibrary libraryscreening screeningat atSwiss Swiss TPH, TPH,Inst. Inst.Pasteur PasteurKK
Lead Leadidentification identification
Medicine Medicine
Bayer Bayer
Company company
Lampit, Lampit,Nifurtimox Nifurtimoxpediatric pediatric(dosing (dosingin inchildren) children)
Phase PhaseIII III
Medicine Medicine
Development of treatments Development of treatments
Lead optimization Lead optimization
Medicine Medicine
Screening program Screening program Screening program (Natural Products Library) Screening program (Natural Products Library) E1224 E1224
Hit identification Hit identification Hit identification Hit identification Phase II Phase II
Medicine Medicine Medicine Medicine Medicine Medicine
DNDi, GHIT (Shionogi, DNDi, GHIT, (Shionogi,GHIT) Takeda, AstraZeneca, Takeda, AstraZeneca, GHIT)
NTD Drug Discovery Booster (DDB-Chagas) NTD Drug Discovery Booster (DDB-Chagas)
Lead generation Lead generation
Medicine Medicine
Broad Inst., GHIT Broad Inst., GHIT
Focused compound library screening Focused compound library screening
Drug discovery Drug discovery (optimization) (optimization)
Medicine Medicine
SVI, Baylor College, Aeras, SVI, GHITBaylor College, Aeras, GHIT
Adjuvant to support vaccine development: Adjuvant to support vaccine development: Chagas vaccine with SVI Chagas vaccine with SVI Adjuvant to support vaccine development: Chagas vaccine with Fiocruz Adjuvant to support vaccine development: Chagas vaccine with Fiocruz Lead optimization project Lead optimization project Lead optimization III for Chagas disease Lead optimization III for Chagas disease
Preclinical Preclinical
Vaccine Vaccine
Preclinical Preclinical
Vaccine Vaccine
Lead optimization Lead optimization Lead optimization Lead optimization
Medicine Medicine Medicine Medicine
Lead identification Lead identification
Medicine Medicine
Lead identification Lead identification
Medicine Medicine
Discovery Discovery
Medicine Medicine
Discovery (tool) Basic research
Medicine Medicine
Lead identification Discovery
Medicine Medicine
Drug discovery Discovery
Medicine Medicine
Drug discovery Basic research
Medicine Medicine
Celgene Celgene Daiichi Sankyo Daiichi Sankyo
Eisai Eisai
DNDi, Antwerp Antwerp Uni, Uni, Epichem, Epichem, DNDi, Monash Uni Monash Uni GHIT, DNDi GHIT, DNDi DNDi DNDi DNDi, GHIT DNDi, GHIT
Fiocruz, GHIT Fiocruz, GHIT
GlaxoSmithKline GlaxoSmithKline
Dundee Uni Dundee Uni Wellcome Wellcome Wellcome/Dundee Uni (Drug Discovery Unit) Wellcome/Dundee Uni (Drug Discovery Unit) Wellcome Wellcome TCOLF, Calibr TCOLF, Calibr
Merck
TCOLF,Swiss LSHTM DNDi, TPH
MSD
DNDi TCOLF, Georgia Uni
Hit Hitto tolead Leadidentification identification Wellcome & Dundee Uni (Drug Discovery Unit) Hit to lead identification Hit to Lead identification Wellcome Develop novel therapies to prevent and treat Develop&novel therapies to prevent and treat Chagas leishmaniasis Chagas & leishmaniasis Mode of action and target identification of Concept generation hit finding anti-Chagasic compounds Targeted screening structure–activity Rapid selection of inand vivohit active antirelationship (SAR) development Trypanosoma cruzi compounds
company DNDi, Swiss TPH
Chagas disease project 1: developing safe Identify new molecules using high throughput treatment for Chagas disease screening of molecular libraries and genotypic targets using CRISPR Cas9 technologies Chagas disease project 2: developing safe treatment for Chagas disease Concept generation hit finding
CDIPD (UCSD), WIPO DNDi Re:Search
PDE5 In vivoinhibitors POC
Drug discovery Discovery
Medicine Medicine
CONICET DNDi
Targeted screening and hit structure–activity Compound screening relationship (SAR) development
Leadidentification optimization Lead
Medicine Medicine
Novartis
DNDi Wellcome
Focused compound library screening Developing safe treatment for Chagas disease
Lead generation Drug discovery
Medicine Medicine
Shionogi Sanofi
GHIT, DNDi DNDi
NTD Drug Discovery Booster Focused compound library screening
Drug discovery Lead generation
Medicine Medicine
Shionogi
DNDi, GHIT GHIT, DNDi
Compound screeningBooster NTD Drug Discovery
Drug discovery Drug (leaddiscovery generation)
Medicine Medicine
DNDi, GHIT GHIT DNDi,
Compound screening Booster NTD Drug Discovery
Drug Drugdiscovery discovery (lead (leadgeneration) generation)
Medicine Medicine
DNDi, GHIT trypanosomiasis (Chagas NTD Drug Discovery Booster Total R&D projects for American disease): 27
Drug discovery (lead generation)
Medicine
Janssen (J&J) Novartis Merck Pfizer MSD Sanofi
Takeda Takeda
company GHIT, DNDi
Total R&D projects for American trypanosomiasis (Chagas disease): 28 21
CHIKUNGUNYA DISE A SE IMPAC T 19,20 Chikungunya is a viral disease usually transmitted to humans by infected mosquitoes Ae. aegypti and Ae. albopictus. Other insect vectors include species of A. furcifer-taylori group and A. luteocephalus. There is evidence that some animals, including non-primates, rodents, birds, and small mammals, may act as reservoirs. The disease causes fever and severe joint pain. Other symptoms include muscle pain, joint swelling, headache, nausea, fatigue, and rash. Chikungunya disease does not often result in death, but the symptoms can be severe and disabling. Some clinical signs are shared with dengue, and it can be misdiagnosed in areas where dengue is common. There is no cure for the disease. Treatment is focused on relieving the symptoms.
KE Y FAC TS21, 22 • I n 2016, about 31,000 cases were reported to the Pan American Health Organization. •P eople at highest risk for more severe disease include newborns, elderly (≥65 years old), and people with medical conditions such as high blood pressure, diabetes, or heart disease. •S ymptoms usually begin 3-7 days after being bitten by an infected mosquito. • Ae. aegypti mosquitoes are confined within the tropics and sub-tropics, Ae. albopictus kind has spread from Asia to become established in areas of Africa, Europe, and the Americas, in the recent decades.
CURRENT R&D PROJEC TS
COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
Sanofi
Vanderbilt Uni
Discovery: operations research
Lead optimization
Medicine
Celgene
A-WOL (Wolbachia), NEB
Compound screening
Screening
Medicine
MSD
USAMRIID
Targeted compound screening
Lead identification
Medicine
Takeda
Zydus Cadilla
Development
Preclinical & Phase I
Vaccine
Total R&D projects for Chikungunya (C): 4
19 https://www.cdc.gov/chikungunya/symptoms/ 20 http://www.who.int/mediacentre/factsheets/fs327/en/
22
21 https://www.cdc.gov/chikungunya/symptoms/ 22 http://www.who.int/mediacentre/factsheets/fs327/en/
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
AbbVie
DNDi
Compound screening, preclinical support, technical consulting
Lead identification
Medicine
Astellas
AIST
Discovery of anti-protozoan parasite drugs for Trypanosoma cruzi
Discovery
Medicine
AstraZeneca
DNDi
Focused compound library screening at Swiss TPH, Inst. Pasteur K
Lead identification
Medicine
Bayer
company
Lampit, Nifurtimox pediatric (dosing in children)
Phase III
Medicine
Development of treatments
Lead optimization
Medicine
GHIT, DNDi
Screening program
Hit identification
Medicine
DNDi
Screening program (Natural Products Library)
Hit identification
Medicine
DNDi, GHIT
E1224
Phase II
Medicine
DNDi, GHIT, (Shionogi, Takeda, AstraZeneca, GHIT)
NTD Drug Discovery Booster (DDB-Chagas)
Lead generation
Medicine
Broad Inst., GHIT
Focused compound library screening
Drug discovery (optimization)
Medicine
SVI, Baylor College, Aeras, GHIT
Adjuvant to support vaccine development: Chagas vaccine with SVI
Preclinical
Vaccine
Fiocruz, GHIT
Adjuvant to support vaccine development: Chagas vaccine with Fiocruz
Preclinical
Vaccine
Dundee Uni
Lead optimization project
Lead optimization
Medicine
Wellcome
Lead optimization III for Chagas disease
Lead optimization
Medicine
Wellcome/Dundee Uni (Drug Discovery Unit)
Hit to Lead identification Wellcome & Dundee Uni (Drug Discovery Unit)
Lead identification
Medicine
Wellcome
Hit to Lead identification Wellcome
Lead identification
Medicine
TCOLF, Calibr
Develop novel therapies to prevent and treat Chagas & leishmaniasis
Discovery
Medicine
Merck
DNDi, Swiss TPH
Concept generation hit finding
Basic research
Medicine
MSD
DNDi
Targeted screening and hit structure–activity relationship (SAR) development
Lead identification
Medicine
company
Chagas disease project 1: developing safe treatment for Chagas disease
Drug discovery
Medicine
company
Chagas disease project 2: developing safe treatment for Chagas disease
Drug discovery
Medicine
CDIPD (UCSD), WIPO Re:Search
PDE5 inhibitors
Drug discovery
Medicine
CONICET
Compound screening
Lead optimization
Medicine
DNDi
Focused compound library screening
Lead generation
Medicine
GHIT, DNDi
NTD Drug Discovery Booster
Drug discovery
Medicine
DNDi, GHIT
Compound screening
Drug discovery (lead generation)
Medicine
DNDi, GHIT
NTD Drug Discovery Booster
Drug discovery (lead generation)
Medicine
Celgene
Daiichi Sankyo
Eisai
GlaxoSmithKline
DNDi, Antwerp Uni, Epichem, Monash Uni
Novartis
Pfizer
Sanofi Shionogi
Takeda
Total R&D projects for American trypanosomiasis (Chagas disease): 27
23
DENGUE Dengue hemorrhagic fever DISE A SE IMPAC T 23 Dengue is a mosquito-borne viral infection which causes flu-like illness, and occasionally develops into a potentially lethal complication – severe dengue. The global incidence of dengue has grown dramatically in recent decades. About half of the world’s population is now at risk. There is no specific treatment for dengue/severe dengue. Dengue prevention and control depends on effective vector control measures. A dengue vaccine has been licensed by several National Regulatory Authorities for use in people 9-45 years of age living in endemic settings.
KE Y FAC TS24 • An estimated 390 million dengue infections occur worldwide each year, with about 96 million resulting in illness. • Dengue is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas. • Severe dengue is a leading cause of serious illness and death among children in some Asian and Latin American countries. • Early detection and access to proper medical care lowers fatality rates below 1%.
23 http://www.who.int/mediacentre/factsheets/fs117/en/ 24 https://www.cdc.gov/chikungunya/symptoms/
24
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
COMPA N Y AbbVie
PA RTNER S DNDi
PROJEC T Compound screening, preclinical support, technical consulting
PH A SE Lead identification
T Y PE Medicine
Astellas Celgene
AIST A-WOL (Wolbachia), NEB
Discovery of anti-protozoan parasite drugs for Trypanosoma cruzi Compound screening
Discovery Screening
Medicine Medicine
AstraZeneca
DNDi
Focused compound library screening at Swiss TPH, Inst. Pasteur K
Lead identification
Medicine
Bayer
company WRAIR, Fiocruz DNDi, Antwerp Uni, Epichem,
Lampit, pediatric (dosing in children) Dengue Nifurtimox purified and inactivated virus vaccine candidate
Phase Phase III I (WRAIR antigens)
Medicine Vaccine
Development of treatments
Lead optimization
Medicine
DNDi, GHIT
E1224
Hit identification Preclinical (GlaxoSmithKline Hit identification antigens) Phase II
Medicine
WRAIR, Fiocruz DNDi
Screening program Dengue purified and inactivated virus Screening program (Natural Products Library) vaccine candidate
Celgene
Daiichi Sankyo GlaxoSmithKline
Monash Uni GHIT, DNDi
Vaccine Medicine Medicine
DNDi, GHIT, (Shionogi, Takeda, AstraZeneca, GHIT) WRAIR, Fiocruz Broad Inst., GHIT
Dengue therapeutic antibody Focused compound library screening
SVI, Baylor College, Aeras, GHIT Wellcome, KU Leuven
Adjuvant to support vaccine development: Chagas vaccine with SVI Discovery new anti-viral small molecules
Preclinical Discovery
Vaccine Medicine
Fiocruz, GHIT
Adjuvant to support vaccine development: Chagas vaccine with Fiocruz
Preclinical
Vaccine
Dundee Uni Company Wellcome
Lead optimization project Tetravalent subunit Lead optimization III for Chagas disease
Lead optimization Phase I Lead optimization
Medicine Vaccine Medicine
Wellcome/Dundee Uni (Drug Discovery Unit) NIAID Wellcome
Hit to Lead identification Wellcome & Dundee Uni (Drug Discovery Unit) Tetravalent live attenuated Hit to Lead identification Wellcome
Lead identification Late stage preclinical Lead identification
Medicine Vaccine Medicine
TCOLF, Calibr
Develop novel therapies to prevent and treat Chagas & leishmaniasis
Discovery
Medicine
Merck
USAMRIID DNDi, Swiss TPH
Target compound Concept generation hit finding
Lead identification Basic research
Medicine Medicine
MSD
DNDi
Targeted screening and hit structure–activity relationship (SAR) development
Lead identification
Medicine
Novartis
Company company
Discovering newproject anti-viral treatmentssafe Chagas disease 1: developing treatment for Chagas disease
Drug discovery Drug discovery
Medicine Medicine Medicine
PDE5 inhibitors
Drug discovery Phase III (efficacy completed) Drug discovery
CONICET
Compound screening
Lead optimization
Medicine
Hokkaido University DNDi
Discovering new anti-viral treatment Focused compound library screening
Drug discovery Lead generation
Medicine Medicine
Shionogi
GHIT, DNDi
NTD Drug Discovery Booster
Drug discovery
Medicine
Takeda Takeda
DNDi, GHIT Company
Four-strain screening recombinant viral vaccine Compound (TAK003)
Drug discovery Phasegeneration) III (lead
Medicine Vaccine
DNDi, GHIT
NTD Drug Discovery Booster
Drug discovery (lead generation)
Medicine
Eisai
Janssen (J&J)
GlaxoSmithKline MSD
Novartis company Sanofi Pfizer
Sanofi Shionogi
Company CDIPD (UCSD), WIPO Re:Search
NTD Drug Discovery Booster (DDB-Chagas)
Chagas disease project 2: developing safe treatment for Chagas disease Tetravalent live attenuated chimeric vaccine
Lead generation Late state preclinical Drug discovery (optimization)
Medicine Vaccine Medicine
Vaccine Medicine
Total R&D projects for American trypanosomiasis (Chagas 27 dengue/dengue hemorrhagic fever: disease): 12
25
HUMAN AFRICAN TRYPANOSOMIASIS Sleeping sickness DISE A SE IMPAC T 25 Human African trypanosomiasis (HAT), also known as “sleeping sickness”, is a parasitic disease transmitted by the bite of the “Glossina” insect (tsetse fly). The disease invades the central nervous system, and is predominantly found among the poor populations living in remote rural areas of Africa, exposed to the tsetse fly though activities such as agriculture, fishing, animal husbandry, or hunting. Other methods of transmission include mother-tochild infection through the placenta, mechanical transmission through other blood-sucking insects, and transmission of the parasite through sexual contact.Diagnosis and treatment of the disease is complex and requires specifically skilled staff. Untreated, it is usually fatal. HAT exists in two forms, depending on the parasite involved. Trypanosoma brucei gambiense infects a person for months or years without major signs or symptoms of the disease. The other form, Trypanosoma brucei rhodesiense causes an acute infection with first symptoms appearing within weeks or months.
KE Y FAC TS26, 27 • The disease occurs in 36 sub-Saharan Africa countries, with 3,796 cases recorded in 2014. • Trypanosoma brucei gambiense is found in 24 countries and accounts for more than 98% of reported cases. • Trypanosoma brucei rhodesiense is found in 13 countries in eastern and southern Africa and accounts for under 2% of reported cases. • Uganda is the only country that presents both forms of the disease in separate zones.
25 http://www.who.int/trypanosomiasis_african/disease/en/ 26 http://www.who.int/trypanosomiasis_african/disease/en/
26
27 http://www.who.int/mediacentre/factsheets/fs259/en/
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
COMPA N Y AbbVie
PA RTNER S DNDi
Compound PROJEC T screening, preclinical support, technical consulting
PH A SE Lead identification
TMedicine Y PE
Astellas
AIST
Discovery of anti-protozoan parasite drugs for Trypanosoma cruzi
Discovery
Medicine
AstraZeneca AbbVie
DNDi
Focused compound library screening at Swiss Compound screening TPH, Inst. Pasteur K
Lead identification Screening
Medicine Medicine
Bayer
company
Lampit, Nifurtimox pediatric (dosing in children)
Phase III
Medicine
Celgene
DNDi, Antwerp Uni, Epichem, Monash Uni DNDi, Antwerp Uni, Epichem, Monash Uni GHIT, DNDi
Development of treatments
Lead optimization
Medicine
Development of treatments Screening program
Lead optimization Hit identification
Medicine Medicine
DNDi
Screening program (Natural Products Library)
Hit identification
Medicine
DNDi, GHIT
E1224
Phase II
Medicine
TCOLFGHIT, (Shionogi, DNDi, Takeda, AstraZeneca, GHIT)
Drug discovery NTD Drug Discovery Booster (DDB-Chagas)
Discovery Lead generation
Medicine Medicine
Broad Inst., GHIT
Focused compound library screening
Drug discovery (optimization)
Medicine
SVI, Baylor College, Aeras, TCOLF, NEU, CSIC GHIT
Adjuvant to support vaccine development: T. brucei drug discovery: ADMET and PK Chagas with SVI supportvaccine for hit-to-lead optimization
Preclinical Lead optimization
Vaccine Medicine
Fiocruz, GHIT
Adjuvant to support vaccine development: Chagas vaccine with Fiocruz
Preclinical
Vaccine
Dundee Uni
Lead optimization project
Lead optimization
Medicine
Wellcome TCOLF, Monash Uni
Hit tooptimization lead optimization kinetoplastid Lead III for for Chagas disease diseases: single agents for Chagas and HAT
Lead optimization Discovery
Medicine Medicine
Wellcome/Dundee Uni (Drug Discovery Unit)
Hit to Lead identification Wellcome & Dundee Uni (Drug Discovery Unit)
Lead identification
Medicine
Wellcome
Hit to Lead identification Wellcome
Lead identification
Medicine
Merck
DNDi, Swiss TCOLF, CalibrTPH
Develop novel therapies to prevent and treat Concept generation hit finding Chagas & leishmaniasis
Basic research Discovery
Medicine Medicine
Merck
DNDi, Swiss TPH
Concept generation hit finding
Basic research
Medicine
MSD
DNDi
Targeted screening and hit structure–activity relationship (SAR) development Discovering (D) new affordable and adaptable NCEsproject 1: developing safe Chagas disease treatment for Chagas disease
Lead identification Drug discovery (lead optimization) Drug discovery
Medicine Medicine
company
Chagas disease project 2: developing safe treatment for Chagas disease
Drug discovery
Medicine
CDIPD DNDi (UCSD), WIPO Re:Search
Fexinidazole (antiprotozoal compound) PDE5 inhibitors
Phasediscovery II / III Drug
Medicine Medicine
CONICET
Compound screening
Lead optimization
Medicine
DNDi
Focused compound library screening
Lead generation
Medicine
DNDi, DNDi GHIT GHIT,
Compound screeningBooster NTD Drug Discovery
Lead identification Drug discovery
Medicine Medicine
DNDi, GHIT
Compound screening
Drug discovery (lead generation)
Medicine
Drug discovery (lead generation)
Medicine
Celgene Daiichi Sankyo
Eisai GlaxoSmithKline
GlaxoSmithKline
Novartis
Wellcome company
Novartis
Sanofi Pfizer
Sanofi Takeda Shionogi
Takeda DNDi, GHIT NTD Drug Discovery Booster Total R&D projects for Human African trypanosomiasis (sleeping sickness): 9
Medicine
Total R&D projects for American trypanosomiasis (Chagas disease): 27
27
LEISHMANIASIS DISE A SE IMPAC T 28,29 Leishmaniasis exists in three main forms – visceral (also known as “kala-azar”), a lethal form of the disease, cutaneous (the most common), and mucocutaneous. Cutaneous leishmaniasis usually presents as ulcers on exposed body parts (arms, legs, face). Mucocutaneous leishmaniasis affects the skin and mucous membrane causing severe deformations. Leishmaniasis is caused by the protozoan Leishmania parasites, which are transmitted by the bite of infected female phlebotomine sandflies. The disease affects some of the poorest people on earth, and is associated with malnutrition, population displacement, poor housing, a weak immune system and lack of financial resources. Leishmaniasis is also linked to environmental changes such as deforestation, building of dams, irrigation schemes, and urbanization.
KE Y FAC TS30, 31 • A n estimated 900,000 to 1.3 million new cases occur annually with around 20,000 to 30,000 deaths occurring in 98 countries. • More than 20 species of the kinetoplastid protozoan parasite Leishmania can be transmitted to humans by some 30 species of phlebotomine sandflies. • O ver 90% of new cases of visceral leishmaniasis occur within the 7 most affected countries – Bangladesh, Brazil, Ethiopia, India, Kenya, Nepal, and Sudan. • The majority of cases of cutaneous leishmaniasis occur in 10 countries – Afghanistan, Algeria, Brazil, Colombia, Costa Rica, Ethiopia, Iran, Peru, Syria, and Sudan.
28 http://www.dndi.org/diseases-projects/leishmaniasis/ 29 http://www.who.int/mediacentre/factsheets/fs375/en/
28
30 http://www.dndi.org/diseases-projects/leishmaniasis/ 31 http://www.who.int/mediacentre/factsheets/fs375/en/
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
AbbVie
DNDi
Compound screening, preclinical support, technical consulting
Discovery
Medicine
AstraZeneca
DNDi
Focused compound library screening at Inst. Pasteur K, Dundee Uni, Swiss TPH
Lead identification
Medicine
Celgene
LSHTM, DNDi
Development of treatments
Lead optimization
Medicine
GHIT, DNDi
Screening program
Hit identification
Medicine
DNDi
Screening program (Natural Products Library)
Hit identification
Medicine
DNDi, GHIT (Shionogi, Takeda, AstraZeneca)
NTD Drug Discovery Booster (DDBLeishmaniasis)
Lead generation
Medicine
Wellcome/ Dundee Uni (Drug Discovery Unit)
Hit to lead identification
Lead identification
Medicine
Wellcome
Hit to lead identification
Lead identification
Medicine
TCOLF, Calibr
Develop novel therapies to prevent and treat Chagas & leishmaniasis
Discovery
Medicine
Wellcome/ Dundee Uni (Drug Discovery Unit)
Lead optimization I for visceral leishmaniasis
Lead optimization
Medicine
Wellcome/ Dundee Uni (Drug Discovery Unit)
Lead optimization II for visceral leishmaniasis
Lead optimization
Medicine
TCOLF, Uni Leon, CBMSO
In-vitro screening for treating leishmaniasis
Discovery
Medicine
Merck
DNDi, Swiss TPH
Concept generation hit finding
Basic research
Medicine
MSD
DNDi
Target screening and hit structure–activity relationship (SAR) development
Lead identification
Medicine
Novartis
Wellcome
Leishmaniasis project: discovering a superior treatment
Drug discovery
Medicine
DNDi
Focused compound library screening
Lead generation
Medicine
DNDi
Compound screening
Lead identification
Medicine
GHIT, DNDi
NTD Drug Discovery Booster
Drug discovery
Medicine
DNDi, GHIT
Compound screening
Drug discovery (lead generation)
Medicine
DNDi, GHIT
NTD Drug Discovery Booster
Drug discovery (lead generation)
Medicine
DNDi, GHIT
Lead optimization of the aminopyrazole series for visceral leishmaniasis
Drug discovery (lead optimization)
Medicine
Daiichi Sankyo
Eisai
GlaxoSmithKline
Sanofi
Shionogi
Takeda
Total R&D projects for leishmaniasis: 21 29
LYMPHATIC FILARIASIS DISE A SE IMPAC T 32 Lymphatic filariasis (elephantiasis) is caused by infection with nematode parasites (roundworms) of the family Filariodidea. There are three types of these thread-like filarial worms: Wuchereria bancrofti, Brugia malayi, and Brugia timori. The disease can result in an altered lymphatic system and the abnormal enlargement of body parts (lymphedema), causing pain, severe disability, and social stigma. Infection occurs when filarial parasites are transmitted to humans through mosquitoes. Infection is usually acquired in childhood causing hidden damage to the lymphatic system and leading to eventual permanent disability. Lymphatic filariasis can be eliminated by stopping the spread of infection through preventive chemotherapy with single doses of two medicines for persons living in areas where the infection is present. A basic, recommended package of care can alleviate suffering and prevent further disability among lymphatic filariasis patients.
KE Y FAC TS33 • A n estimated 15 million people are afflicted with lymphedema globally. • 1.10 billion people in 55 countries worldwide remain threatened by lymphatic filariasis and require preventive chemotherapy to stop the spread of this parasitic infection. • 5.63 billion treatments have been delivered to stop the spread of infection since 2000. • Wuchereria bancrofti is responsible for 90% of the cases. • 25 million men globally suffer with genital form of the disease. • 8 out of 73 endemic countries are currently under surveillance to demonstrate that elimination has been achieved.
32 http://www.dndi.org/diseases-projects/chagas/ 33 http://www.who.int/mediacentre/factsheets/fs102/en/
30
CURRENT R&D PROJEC TS
COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
LSTM
Collaborative preclinical development program
Discovery
Medicine
DNDi
Compound screening
Lead identification
Medicine
A-WOL, LSTM
Focused compound library screening and DMPK support
Lead identification
Medicine
Monclair State Uni, DNDi, NPIMR, Bonn Uni
Development of treatments
Lead optimization
Medicine
A-WOL (Wolbachia), NEB
Compound screening
Screening
Medicine
UCSD, UCSF, LSTM, Bonn Uni, AbbVie, Anacor, Johnson & Johnson, Eisai, Merck, Calibr, DNDi, BMGF
Development of Macrofilaricide Drug Accerelator (MacDA)
Lead identification
Medicine
Company
Development of diethylcarbamazine citrate (DEC)
Post-approval surveillance (stability study for shelf-life extension)
Medicine
LSTM, Liv Uni, GHIT
Novel compounds for anti-Wolbachia
Lead optimization
Medicine
DNDi, NPIMR
Concept generation hit finding
Basic research
Medicine
DNDi
Target compound screening
Lead identification
Medicine
DNDi
In vivo POC studies macrofilaricide drug accelerator
Discovery
Medicine
DNDi
Focused compound library screening
Lead generation
Medicine
AbbVie
AstraZeneca
Celgene
Eisai
Merck
MSD
Sanofi
Total R&D projects for lymphatic filariasis: 12
31
MYCETOMA DISE A SE IMPAC T 34,35 Mycetoma (also known as Madura foot / maduromycosis / maduramycosis) is a slow-growing bacterial or fungal infection, which exists in two forms: Actinomycetoma and Eumycetoma. It is a chronic, progressively destructive morbid inflammatory disease usually of the foot but any part of the body can be affected. Infection is most probably acquired when the causative organisms of Mycetoma enter the body through minor trauma or a penetrating injury. The disease is characterized by a triad of painless subcutaneous mass, multiple sinuses, and discharge containing grains. It usually spreads to involve the skin, deep structures, and bone, resulting in destruction, deformity, and loss of function, which may be fatal. Mycetoma commonly involves the extremities, back, and gluteal region. There is a clear relationship between Mycetoma and individuals who walk barefoot. The disease has numerous adverse medical, health and socioeconomic impacts on patients, communities, and health authorities.
KE Y FAC TS36, 37 •M ycetoma commonly affects young adults, particularly males aged between 20 and 40 years. •A ctinomycetoma form is a bacterial infection with an approximate 90% cure rate using antibiotics, Eumycetoma form is a fungal infection with a 25-35% cure rate with antifungals and surgery. •A pproximately 40% of Mycetoma cases worldwide are Eumycotic. •C ausative organisms of Mycetoma are distributed worldwide but are endemic in tropical and subtropical areas in the “Mycetoma belt”, which includes the Bolivarian Republic of Venezuela, Chad, Ethiopia, India, Mauritania, Mexico, Senegal, Somalia, Sudan, and Yemen.
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
Eisai
DNDi
E1224
Clinical (preparation for phase II)
Medicine
Total R&D projects for mycetoma: 1
34 http://www.who.int/buruli/mycetoma/en/ 35 http://www.dndi.org/diseases-projects/mycetoma/
32
36 http://www.who.int/buruli/mycetoma/en/ 37 http://www.dndi.org/diseases-projects/mycetoma/
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
AbbVie
DNDi
Compound screening, preclinical support, technical consulting
Lead identification
Medicine
Astellas
AIST
Discovery of anti-protozoan parasite drugs for Trypanosoma cruzi
Discovery
Medicine
AstraZeneca
DNDi
Focused compound library screening at Swiss TPH, Inst. Pasteur K
Lead identification
Medicine
Bayer
company
Lampit, Nifurtimox pediatric (dosing in children)
Phase III
Medicine
Development of treatments
Lead optimization
Medicine
GHIT, DNDi
Screening program
Hit identification
Medicine
DNDi
Screening program (Natural Products Library)
Hit identification
Medicine
DNDi, GHIT
E1224
Phase II
Medicine
DNDi, GHIT, (Shionogi, Takeda, AstraZeneca, GHIT)
NTD Drug Discovery Booster (DDB-Chagas)
Lead generation
Medicine
Broad Inst., GHIT
Focused compound library screening
Drug discovery (optimization)
Medicine
SVI, Baylor College, Aeras, GHIT
Adjuvant to support vaccine development: Chagas vaccine with SVI
Preclinical
Vaccine
Fiocruz, GHIT
Adjuvant to support vaccine development: Chagas vaccine with Fiocruz
Preclinical
Vaccine
Dundee Uni
Lead optimization project
Lead optimization
Medicine
Wellcome
Lead optimization III for Chagas disease
Lead optimization
Medicine
Wellcome/Dundee Uni (Drug Discovery Unit)
Hit to Lead identification Wellcome & Dundee Uni (Drug Discovery Unit)
Lead identification
Medicine
Wellcome
Hit to Lead identification Wellcome
Lead identification
Medicine
TCOLF, Calibr
Develop novel therapies to prevent and treat Chagas & leishmaniasis
Discovery
Medicine
Merck
DNDi, Swiss TPH
Concept generation hit finding
Basic research
Medicine
MSD
DNDi
Targeted screening and hit structure–activity relationship (SAR) development
Lead identification
Medicine
company
Chagas disease project 1: developing safe treatment for Chagas disease
Drug discovery
Medicine
company
Chagas disease project 2: developing safe treatment for Chagas disease
Drug discovery
Medicine
CDIPD (UCSD), WIPO Re:Search
PDE5 inhibitors
Drug discovery
Medicine
CONICET
Compound screening
Lead optimization
Medicine
DNDi
Focused compound library screening
Lead generation
Medicine
GHIT, DNDi
NTD Drug Discovery Booster
Drug discovery
Medicine
DNDi, GHIT
Compound screening
Drug discovery (lead generation)
Medicine
DNDi, GHIT
NTD Drug Discovery Booster
Drug discovery (lead generation)
Medicine
Celgene
Daiichi Sankyo
Eisai
GlaxoSmithKline
DNDi, Antwerp Uni, Epichem, Monash Uni
Novartis
Pfizer
Sanofi Shionogi
Takeda
Total R&D projects for American trypanosomiasis (Chagas disease): 27
33
ONCHOCERCIASIS River blindness DISE A SE IMPAC T 38 Onchocerciasis or “river blindness” is caused by the parasitic worm Onchocerca volvulus. It is transmitted to humans through exposure to repeated bites of infected blackflies of the genus Simulium. Symptoms are caused by the microfilariae, which move around the human body in the subcutaneous tissue and induce intense inflammatory responses when they die. Infected people commonly suffer from severe itching, disfiguring skin conditions, and visual impairment, as well as permanent blindness.
KE Y FAC TS39 • More than 99% of infected people live in 31 African countries. • In July 2015, Mexico became the third country in the world after Colombia in 2013 and Ecuador in 2014 to be declared free of onchocerciasis after successfully implementing elimination activities for decades.
38 http://www.who.int/mediacentre/factsheets/fs374/en/ 39 http://www.who.int/mediacentre/factsheets/fs374/en/
34
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
LSTM
Collaborative discovery program
Discovery
Medicine
DNDi
Compound screening
Discovery
Medicine
LSTM, DNDi
Preclinical candidate, scientific engagement
Preclinical
Medicine
Macrofilaricide Drug Accelerator (MacDA)
Compound screening
Discovery
Medicine
AstraZeneca
A-WOL, LSTM
Focused library screening and DMPK support
Lead identification
Medicine
Bayer
DNDi
Development of emodepside
Preclinical
Medicine
Monclair State Uni, DNDi, NPIMR, Bonn Uni
Development of treatments
Lead optimization
Medicine
A-WOL (Wolbachia), NEB
Compound screening
Screening
Medicine
LSTM, Liv Uni, GHIT
Novel compounds for anti-Wolbachia
Lead optimization
Medicine
UCSD, UCSF, LSTM, Bonn Uni, AbbVie, Anacor, Johnson & Johnson, Eisai, Merck, Calibr, DNDi, BMGF
Development of treatments with Macrofilaricide Drug Accelerator (MacDA)
Lead identification
Medicine
DNDi, NPIMR
Concept generation hit finding
Basic research
Medicine
Buea Uni, WIPO Re:Search
Screening for macrofilaricides for onchocerciasis
Screening
Medicine
Macrofilaricide Drug Accelerator (MacDA)
Compound
Discovery
Medicine
DNDi
Target compound screening
Lead identification
Medicine
DNDi
Focused compound library screening
Lead generation
Medicine
AbbVie
Celgene
Eisai
Merck
MSD
Sanofi
Total R&D projects for onchocerciasis: 15
35
RABIES DISE A SE IMPAC T40 The rabies virus is contracted through wounds (e.g. scratches from an infected animal) or by direct contact with mucosal surfaces (e.g. bite from an infect animal). Once inside the body, the virus replicates in the bitten muscle and gains access to motor endplates and motor axons to reach the central nervous system. The virus then travels to the central nervous system, where a majority of the clinical symptoms manifest as an acute encephalitis or meningoencephalitis. Half of the global population lives in canine rabiesendemic areas and is considered at risk for contracting rabies.
KE Y FAC TS 41 •A n average of 60,000 people die from rabies annually, and more than 15 million people receive post-exposure prophylaxis every year, averaging to 40% of children in Asia and Africa aged 5-14 years. • I n more than 99% of all cases of human rabies, the virus is transmitted via dogs. •T he incubation period averages 2-3 months and death occurs within 2 weeks after the appearance of clinical symptoms if intensive care is not sought. •4 out of every 10 deaths due to rabies occur in children younger than 15 years old.
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
Sanofi
Company
VRVg: purified serum-free vero cell rabies vaccine
Phase III
Medicine
Total R&D projects for rabies: 1
40 http://www.who.int/rabies/human/en/ 41 http://www.who.int/rabies/human/en/
36
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
AbbVie
DNDi
Compound screening, preclinical support, technical consulting
Lead identification
Medicine
Astellas
AIST
Discovery of anti-protozoan parasite drugs for Trypanosoma cruzi
Discovery
Medicine
AstraZeneca
DNDi
Focused compound library screening at Swiss TPH, Inst. Pasteur K
Lead identification
Medicine
Bayer
company
Lampit, Nifurtimox pediatric (dosing in children)
Phase III
Medicine
Development of treatments
Lead optimization
Medicine
GHIT, DNDi
Screening program
Hit identification
Medicine
DNDi
Screening program (Natural Products Library)
Hit identification
Medicine
DNDi, GHIT
E1224
Phase II
Medicine
DNDi, GHIT, (Shionogi, Takeda, AstraZeneca, GHIT)
NTD Drug Discovery Booster (DDB-Chagas)
Lead generation
Medicine
Broad Inst., GHIT
Focused compound library screening
Drug discovery (optimization)
Medicine
SVI, Baylor College, Aeras, GHIT
Adjuvant to support vaccine development: Chagas vaccine with SVI
Preclinical
Vaccine
Fiocruz, GHIT
Adjuvant to support vaccine development: Chagas vaccine with Fiocruz
Preclinical
Vaccine
Dundee Uni
Lead optimization project
Lead optimization
Medicine
Wellcome
Lead optimization III for Chagas disease
Lead optimization
Medicine
Wellcome/Dundee Uni (Drug Discovery Unit)
Hit to Lead identification Wellcome & Dundee Uni (Drug Discovery Unit)
Lead identification
Medicine
Wellcome
Hit to Lead identification Wellcome
Lead identification
Medicine
TCOLF, Calibr
Develop novel therapies to prevent and treat Chagas & leishmaniasis
Discovery
Medicine
Merck
DNDi, Swiss TPH
Concept generation hit finding
Basic research
Medicine
MSD
DNDi
Targeted screening and hit structure–activity relationship (SAR) development
Lead identification
Medicine
company
Chagas disease project 1: developing safe treatment for Chagas disease
Drug discovery
Medicine
company
Chagas disease project 2: developing safe treatment for Chagas disease
Drug discovery
Medicine
CDIPD (UCSD), WIPO Re:Search
PDE5 inhibitors
Drug discovery
Medicine
CONICET
Compound screening
Lead optimization
Medicine
DNDi
Focused compound library screening
Lead generation
Medicine
GHIT, DNDi
NTD Drug Discovery Booster
Drug discovery
Medicine
DNDi, GHIT
Compound screening
Drug discovery (lead generation)
Medicine
DNDi, GHIT
NTD Drug Discovery Booster
Drug discovery (lead generation)
Medicine
Celgene
Daiichi Sankyo
Eisai
GlaxoSmithKline
DNDi, Antwerp Uni, Epichem, Monash Uni
Novartis
Pfizer
Sanofi Shionogi
Takeda
Total R&D projects for American trypanosomiasis (Chagas disease): 27
37
SCHISTOSOMIASIS DISE A SE IMPAC T42 Schistosomiasis is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma. People are infected during routine agricultural, domestic, occupational and recreational activities, which expose them to infested water. There are two major forms of schistosomiasis – intestinal and urogenital – caused by five main species of blood fluke. Intestinal schistosomiasis can result in abdominal pain, diarrhea, blood in the stool, and enlargement of organs. The urogenital schistosomiasis results in blood in urine, fibrosis of the bladder and ureter, kidney damage, and even bladder cancer among other symptoms. The disease may have long-term irreversible consequences, including infertility. Schistosomiasis control focuses on reducing disease through periodic, large-scale population pharmaceutical treatments, adequate sanitation, and snail control.
KE Y FAC TS 43 • The disease causes an estimated 20,000 deaths globally each year. • In 2014, at least 258 million people required preventive treatment for schistosomiasis with 90% of people living in Africa. • More than 61.6 million people were reported to have been treated in 2014. • In 2014, transmission of the disease has been reported from 78 countries.
42 http://www.who.int/mediacentre/factsheets/fs115/en/ 43 http://www.who.int/mediacentre/factsheets/fs115/en/
38
CURRENT R&D PROJEC TS
COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
Astellas & Merck
Swiss TPH, Lygature, Fiocruz (Farmanguinhos), Simcyp, SCI
Pediatric praziquantel formulation
Phase II
Medicine
Swiss TPH, helminGuard, McGill Uni
Concept generation: target to hit optimization
Basic research
Medicine
BRI
Pharmacology: praziquantel mode of action
Basic research
Medicine
Company
Praziquantel optimization and prequalification
Clinical trials (Phase I, bioequivalence)
Medicine
UCSD
Targeted screening
Lead identification
Medicine
Merck
MSD
Total R&D projects for schistosomiasis: 5
39
TRACHOMA DISE A SE IMPAC T44 Trachoma is a disease of the eye caused by infection with the bacterium Chlamydia trachomatis. The disease causes irreversible blindness or visual impairment in people. Infection spreads through personal contact (via hands, clothes, or bedding) and by flies that have been in contact with discharge from the eyes or nose of an infected person. With repeated episodes of infection over many years, the eyelashes may be drawn in so that they rub on the surface of the eye, with pain and discomfort and permanent damage to the cornea.
KE Y FAC TS 45 •T he disease is considered a public health problem in 42 countries. •A n estimated 1.9 million people are left blind or visually impaired as a result of the disease. •O ver 200 million people live in trachoma endemic areas and are at risk of trachoma blindness. • I n 2015, more than 185,000 people received surgical treatment for the advanced stage of the disease, and 56 million people were treated with antibiotics.
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
Pfizer
EMCF, ITI
International Trachoma Initiative: Azithromycin, Macrolide antibiotic
Development (manufacturing)
Medicine
Total R&D projects for trachoma: 1
44 http://www.who.int/rabies/human/en/ 45 http://www.who.int/rabies/human/en/
40
CURRENT R&D PROJEC TS COMPA N Y
PA RTNER S
PROJEC T
PH A SE
T Y PE
AbbVie
DNDi
Compound screening, preclinical support, technical consulting
Lead identification
Medicine
Astellas
AIST
Discovery of anti-protozoan parasite drugs for Trypanosoma cruzi
Discovery
Medicine
AstraZeneca
DNDi
Focused compound library screening at Swiss TPH, Inst. Pasteur K
Lead identification
Medicine
Bayer
company
Lampit, Nifurtimox pediatric (dosing in children)
Phase III
Medicine
Development of treatments
Lead optimization
Medicine
GHIT, DNDi
Screening program
Hit identification
Medicine
DNDi
Screening program (Natural Products Library)
Hit identification
Medicine
DNDi, GHIT
E1224
Phase II
Medicine
DNDi, GHIT, (Shionogi, Takeda, AstraZeneca, GHIT)
NTD Drug Discovery Booster (DDB-Chagas)
Lead generation
Medicine
Broad Inst., GHIT
Focused compound library screening
Drug discovery (optimization)
Medicine
SVI, Baylor College, Aeras, GHIT
Adjuvant to support vaccine development: Chagas vaccine with SVI
Preclinical
Vaccine
Fiocruz, GHIT
Adjuvant to support vaccine development: Chagas vaccine with Fiocruz
Preclinical
Vaccine
Dundee Uni
Lead optimization project
Lead optimization
Medicine
Wellcome
Lead optimization III for Chagas disease
Lead optimization
Medicine
Wellcome/Dundee Uni (Drug Discovery Unit)
Hit to Lead identification Wellcome & Dundee Uni (Drug Discovery Unit)
Lead identification
Medicine
Wellcome
Hit to Lead identification Wellcome
Lead identification
Medicine
TCOLF, Calibr
Develop novel therapies to prevent and treat Chagas & leishmaniasis
Discovery
Medicine
Merck
DNDi, Swiss TPH
Concept generation hit finding
Basic research
Medicine
MSD
DNDi
Targeted screening and hit structure–activity relationship (SAR) development
Lead identification
Medicine
company
Chagas disease project 1: developing safe treatment for Chagas disease
Drug discovery
Medicine
company
Chagas disease project 2: developing safe treatment for Chagas disease
Drug discovery
Medicine
CDIPD (UCSD), WIPO Re:Search
PDE5 inhibitors
Drug discovery
Medicine
CONICET
Compound screening
Lead optimization
Medicine
DNDi
Focused compound library screening
Lead generation
Medicine
GHIT, DNDi
NTD Drug Discovery Booster
Drug discovery
Medicine
DNDi, GHIT
Compound screening
Drug discovery (lead generation)
Medicine
DNDi, GHIT
NTD Drug Discovery Booster
Drug discovery (lead generation)
Medicine
Celgene
Daiichi Sankyo
Eisai
GlaxoSmithKline
DNDi, Antwerp Uni, Epichem, Monash Uni
Novartis
Pfizer
Sanofi Shionogi
Takeda
Total R&D projects for American trypanosomiasis (Chagas disease): 27
41
Abbreviations
A BBRE VIATION
PA RTNER’S FULL N A ME
Aeras
Aeras Global TB Vaccine Foundation
AIST
National Institute of Advanced Industrial Science and Technology
Antwerp Uni
University of Antwerp
A-WOL
Anti Wolbachia (A-WOL) Consortium based at the LSTM
Baylor College
Baylor College of Medicine
BMGF
Bill & Melinda Gates Foundation
Bonn Uni
Bonn University
BRI
Biomedical Research Institute
Broad Inst.
Broad Institute
Buea Uni
University of Buea
Calibr
California Institute for Biomedical Research
CBMSO
Centro de Biologia Molecular Severo Ochoa
CSIC
Spanish National Council for Research
DMPK
Drug Metabolism and Pharmacokinetics
DNDi
Drugs for Neglected Diseases initiative
Dundee Uni
Dundee University
EMCF
The Edna McConnell Clark Foundation
Epichem
Epichem Pty Ltd
Farmanguinhos (Fiocruz)
Instituto de Technologia em Fármacos (Fundação Oswaldo Cruz)
Fiocruz
Fundação Oswaldo Cruz
Georgia Uni
University of Georgia
GHIT
Global Health Innovative Technology Fund
ITI
International Trachoma Initiative
Inst. Pasteur K
Institut Pasteur Korea
KU Leuven
Rega Institute KU Leuven
Liv Uni
Liverpool University
LSHTM
London School of Hygiene and Tropical Medicine
A BBRE VIATION
PA RTNER’S FULL N A ME
LSTM
Liverpool School of Tropical Medicine
Lygature
Lygature, Netherlands
MacDA
Macrofilaricide Drug Accelerator
McGill Uni
McGill University
Monash Uni
Monash University
Monclair State Uni
Monclair State University
NEU
Northeastern University
NIAID
National Institute of Allergy and Infectious Diseases
NEB
New England BioLabs
NPIMR
Northwick Park Institute for Medical Research
SCI
Schistosomiasis Control Initiative (Imperial College London)
Simcyp
Simcyp Ltd
SVI
Sabin Vaccine Institute
Swiss TPH
Swiss Tropical and Public Health Institute
TCOLF
Tres Cantos Open Lab Foundation
UCSD
University of California, San Diego
UCSF
University of California, San Francisco
Uni Leon
Universidad de León
USAMRIID
United States Army Medical Research Institute of Infectious Diseases
Vanderbilt Uni
Vanderbilt University
Wellcome
Wellcome Trust
WHO
World Health Organization
WIPO
World Intellectual Property Organization
WRAIR
Walter Reed Army Institute of Research
Photos on cover and on pages 2, 4, 5, 7, 9, 13, 14, 17, 19 are reproduced with the permission of GlaxoSmithKline. 43
ABOUT IFPMA IFPMA represents the research-based pharmaceutical companies and associations across the globe. The research-based pharmaceutical industry’s over 2 million employees research, develop and provide medicines and vaccines that improve the life of patients worldwide. Based in Geneva, IFPMA has official relations with the United Nations and contributes industry expertise to help the global health community find solutions that improve global health.
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