Innovating to Fight Neglected Tropical Diseases

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Doing our part: Innovating to fight Neglected Tropical Diseases April 2017 Designed by ACW, London www.acw.uk.com Contents BIOPHARMACEUTICAL INDUSTRY Scaling Up Access to CONTRIBUTIONS TO THE GLOBAL Existing Treatments FIGHT AGAINST NTDs 16

Staying the Course: A Global Strengthening Health Commitment to Fight NTDs Systems - The scope of the NTD epidemic 4 - The London Declaration 18

Boosting Innovation - Discovery - Pipeline 8 - Funding

R&D PIPELINE FOR NTDs

American trypanosomiasis Mycetoma 20 (Chagas disease) 32 (river blindness)

Chikungunya Onchocerciasis (river blindness) 22 34

Dengue Rabies 24 (dengue hemorrhagic fever) 36

Human African Schistosomiasis trypanosomiasis 26 (sleeping sickness) 38 28 Leishmaniasis 40 Trachoma 30 Lymphatic filariasis 42 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. THE SCOPE OF THE NTD EPIDEMIC Today, the London Declaration’s endorsers have grown to include over 200 organizations3. Although most NTDs are preventable and treatable, they sadly continue to be a heavy burden on the most vulnerable, disadvantaged people in the world. “Today, we have joined together to increase One person in seven suffers from one or more NTDs – comparable to the entire population of Europe – the impact of our investments and build on with the vast majority of cases in low- and middle- the tremendous progress made to date. income countries (LMICs). NTDs are caused by a range of different parasites, This innovative approach must serve as a bacteria and viruses, which primarily thrive in subtropical model for solving other global development climates. They can be painful, blinding and disfiguring; each year they lead to the poor-health, disability challenges and will help millions of people build and death of hundreds of thousands of people. self-sufficiency and overcome the need for aid.” As they are often chronic and disabling, NTDs have enormous educational and economic impacts, keeping Bill Gates, co-chair of the Bill & Melinda Gates Foundation, children out of school and adults out of work. At the start of this millennium, it was estimated that in India at the signing of the London Declaration in 2012 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 Now at the halfway mark of the WHO NTD infected with intestinal worms had a 20% lower Roadmap’s timeline, this publication outlines how probability of school enrolment and, subsequently, the R&D biopharmaceutical industry is contributing a 40% reduction in income as an adult4. to this global agenda, with active research projects to uncover new or improved treatments and vaccines. The landscape of neglected disease control is It also provides context of how these R&D efforts continuously changing. Climate change is driving are part of an integrated approach to combatting diseases beyond their traditional geographies, resulting NTDs, including an unprecedented medicines in outbreaks of dengue and Chagas disease beyond the donation program of 14 billion treatments over tropics. Furthermore, complex changes in demography, ten years and support for local capacity building. 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 DECLARATION

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 DECLARATION 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.

THE SCOPE OF THE NTD EPIDEMIC

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 DECLARATION5

• 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. 1 http://www.who.int/neglected_diseases/NTD_RoadMap_2012_Fullversion.pdf 2 http://unitingtocombatntds.org/sites/default/files/resource_file/london_ • Since the London Declaration, there have been over 7.9 billion tablets declaration_on_ntds.pdf 3 http://unitingtocombatntds.org/endorsements in pharma donations, which is enough for 5 billion treatments. 4 http://www.globalnetwork.org/sites/default/files/Social%20and%20 Economic%20Impact%20Review%20on%20Neglected%20Tropical%20 • 87% of countries in Africa have been fully mapped for the London Diseases%20Hudson%20Institute%20and%20Sabin%20Institute%20 November%202012_1.pdf Declaration’s targeted NTDs. 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 109 active R&D projects to partnerships to build develop the next generation capacity to fight NTDs where of medicines and vaccines they are endemic 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 BOOSTING INNOVATION

DISCOVERY

There has been considerable progress in new technologies, including 1medicines, 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) SOIL-TRANSMITTED LYMPHATIC HELMINTHIASES (2016) FILARIASIS (2013) Dengue is a threat to nearly half of the world’s population, yet Soil-transmitted helminthiases, Lymphatic filariasis is often until recently there was no specific otherwise known as intestinal referred to as elephantiasis, due to treatment or vaccine available to worms, are a chronic and debilitating severe disfigurement, disability, and reduce the burden of this disease. illness with particular impact swelling from fluid build-up caused Dengue is the fastest progressing on children, stunting growth, by improper functioning of the vector-borne disease and can cause impairing cognitive development lymphatic system. Infection massive outbreaks with a disruptive and keeping children out of school. occurs when filarial parasites are effect on healthcare systems. transmitted to humans through The approval of a chewable Mostly asymptomatic, dengue can mosquitoes. An estimated 120 formulation of mebendezole7 also lead to hospitalization, serious million people worldwide live supports global efforts to reduce illness and death among people with the disease. the burden of parasitic infections leaving in endemic areas in Asia in young children. Donations of this The development and distribution Latin America and Africa. treatment are planned to be rolled of diethylcarbamazine citrate The newly approved dengue vaccine6 out towards the WHO’s objective (DEC)8 through large-scale mass presents a major advance towards to provide treatment to over 75% drug administration supports the the achievement of WHO objectives of 870 million at-risk children. WHO target of eliminating the to reducing dengue mortality and disease by 2020. 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 7 7 COMPOUNDS FOR NTDs CURRENTLY UNDERGO LATE STAGE % 109 TESTING 90 109 ACTIVE R&D OVER 90% OF THE ACTIVE PROJECTS FOR NTDs R&D PROJECTS FOR NTDs ARE COLLABORATIVE EFFORTS

To ensure that new generations of improved treatments and interventions are discovered, despite low commercial incentives in the area of NTDs, the biopharmaceutical 50 industry engages in a variety of multi-sectoral research models. The most common model sees NTD R&D through OVER 50 PARTNERS partnerships. This innovative approach has proven to (UNIVERSITIES, NGOs, enable the sharing of expertise and acceleration of research, PUBLIC AND PRIVATE reduced risks and duplications, and sustainable financing. 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 DEVELOPMENT

Early Phase Practical TestingCritical Trials Regulatory Scale-up to Post-Marketing Research Review Manufacturing Surveillance PHASE 0

5,000 - 10,000 250 TE D 5 COMPOUNDS PHASE IV Y TED TION SUBMIT VER A

O ONE MARKETED

APPLIC MEDICINE TION SUBMIT A DRUG

TIONS FILED PHASE I A CH & DRUG DISC Target identiﬁcation (TI) PHASE II APPLIC Lead generation (LG) TIONAL

APPLIC PHASE III

RESEAR Lead identiﬁcation (LI) DRUG

Lead optimization (LO) TENT PA INVESTIGA NEW BASIC

4-6 YEARS 1 YEAR 6-7 YEARS 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 late- stage 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 PARTNERS FOR NTDs

Schistosomiasis Trachoma Current projects: 5 Current projects: 1 Medicines: 5 Medicines: 1 Rabies American trypanosomiasis Current projects: 1 (Chagas disease) Vaccines: 1 Current projects: 28 Medicines: 26 Vaccines: 2 Onchocerciasis (river blindness) Current projects: 15 Medicines: 15

Mycetoma Current projects: 1 Medicines: 1 Chikungunya Current projects: 4 Medicines: 3 Lymphatic ﬁlariasis Vaccines: 1 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

11 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-FINDER report.

12 13 DEDICATED INTERNATIONAL INITIATIVES FOR NTD RESEARCH

GLOBAL HEALTH INNOVATIVE 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 THE EUROPEAN & DEVELOPING COUNTRIES CLINICAL TRIALS PARTNERSHIP (EDCTP) & THE SPECIAL PROGRAMME FOR RESEARCH AND TRAINING IN TROPICAL DISEASES (WHO/TDR), SUPPORTING WIPO RE:SEARCH, A COLLABORATIVE RESEARCHERS AND CLINICAL TRIAL RESEARCH TEAMS PLATFORM TO BOOST R&D FROM LOW- AND MIDDLE-INCOME COUNTRIES (LMICs)

WIPO Re:Search was established in October 2011 by EDCTP and WHO/TDR offer a Clinical Research and Development Fellowship. the World Intellectual Property Organization (WIPO) The overall objective is to strengthen collaboration between research in collaboration with BIO Ventures for Global Health institutions, researchers and clinical staff in LMICs, pharmaceutical (BVGH) and with the active participation of leading companies, and Product Development Partnerships (PDPs)12. pharmaceutical companies. The consortium now consists By working together, they ensure harmonization and synergy through a of over 100 organizations from both the private and Joint Call for Proposals. The host organizations, pharmaceutical companies public sectors, including non-profit organizations and and PDPs train scientists, for a period of up to 24 months to develop specialist academic research institutes. WIPO Re:Search member product development skills not readily taught in academic centers or public organizations share their intellectual property assets research institutions. The fellows are expected to become an important such as compounds and compound libraries, technologies, resource for institutional capacity development, to undertake and expertise, samples, and data to bridge research gaps, manage clinical research in accordance with international regulatory reduce costs of product development, and advance drug, requirements and standards13. vaccine, and diagnostic research and development for NTDs, malaria, and tuberculosis. The fellowship has increased the number of individuals trained and helped facilitate common communication with researchers and clinical To date BVGH has established 105 research collaborations staff, pharmaceutical companies, PDPs and research institutions. through WIPO Re:Search. Collaborations cover a range of areas that include the sharing of data and services IFPMA member companies involved in training fellows for the year (such as access to company research facilities, screening 2015/2016 are: Astellas, Bayer, GlaxoSmithKline, Janssen (Johnson of compounds, hosting of scientists) as well as other & Johnson), Merck, Novartis, and Sanofi. forms of expertise. For more information please visit IFPMA member companies involved in WIPO Re:Search EDTCP: are: Eisai, GlaxoSmithKline, Janssen (Johnson & Johnson), www.edctp.org/call/edctp-tdr-clinical-research-development-fellowships-2/ Merck, MSD, Novartis, Pfizer, Sanofi, and Takeda11. TDR: For more information please visit 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/

14 PHARMACEUTICAL INDUSTRY CENTERS DEDICATED TO NTDs R&D

COMPANY R&D CENTER LOCATION SINCE

AbbVie AbbVie North Chicago, IL 2009

Cambridge Biomedical Campus (CBC) Cambridge, UK 2015

AstraZeneca

Alderley Park* Macclesfield, UK 1999

Celgene Celgene Global Health Summit, NJ, USA 2009

GlaxoSmithKline Diseases of the Developing World center Tres Cantos, Spain 2002

R&D Translational Innovation Platform Merck Geneva, Switzerland 2014 “Global Health”

MSD (operated as Merck & Co., MSD Wellcome Trust Hilleman Laboratories New Delhi, India 2009 Inc. in the USA and Canada)

Novartis Institute for Tropical Diseases (NITD) Singapore** 2002

Novartis Institutes for BioMedical Research Emeryville, CA, USA 2016 Novartis (NIBR)

Genomics Institute of the Novartis Research La Jolla, USA 2010 Foundation (GNF)

Eisai Inc. Andover Research Institute Andover, MA, USA 1987

Eisai Pharmaceuticals India Pvt. Ltd. Visakhapatnam, India 2007 Eisai

Tsukuba Research Laboratories Japan 1982 (Ibaraki Prefecture)

Vaccines (dengue) since the 90s Sanofi Marcy l’Etoile Research & development Campus Lyon, France Medicines since 2015

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.

* The 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 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 2 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. Five of the 10 NTDs covered in the London Declaration By 2020, nearly USD 18 billion can be controlled through what is known as mass drug administration (MDA) – large-scale population treatment worth of medicines will have been with safe and effective medicines to all people living distributed, the largest medicine in high-risk areas. These diseases include: lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted donation the world has ever seen. 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 SCALING UP ACCESS TO EXISTING TREATMENTS

17 STRENGTHENING HEALTH SYSTEMS

NTDs control and elimination is a challenging task with a need for a 3 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. Programs focus on building health services that are accessible and staffed with qualified healthcare workers Political commitment and to enable the delivery of medicines and vaccines down leadership from national the last mile. They also provide people living in endemic areas information to help prevent the spread of infection, programs are paramount. and infrastructure programmes to address water, All projects involve collaboration sanitation and hygiene. So that every effort is made to support the WHO and with national governments and national governments in meetings targets of the NTD community-based platforms. 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

DISEASE IMPACT15,16

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.

KEY FACTS17, 18

• An 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/ 17 http://www.dndi.org/diseases-projects/chagas/ 16 http://www.who.int/mediacentre/factsheets/fs340/en/ 18 http://www.who.int/mediacentre/factsheets/fs340/en/

20 CURRENT R&D PROJECTS

COMPANYCOMPANY PARTNERSPARTNERS PROJECTPROJECT PHASEPHASE TYPETYPE

CompoundCompound screening, screening, preclinical preclinical support, support, AbbVieAbbVie DNDiDNDi LeadLead identification identification MedicineMedicine technicaltechnical consulting consulting

DiscoveryDiscovery of of anti-protozoan anti-protozoan parasite parasite drugs drugs for for AstellasAstellas AISTAIST DiscoveryDiscovery MedicineMedicine TrypanosomaTrypanosoma cruzi cruzi

FocusedFocused compound compound library library screening screening at at Swiss Swiss AstraZenecaAstraZeneca DNDiDNDi LeadLead identification identification MedicineMedicine TPH,TPH, Inst. Inst. Pasteur Pasteur K K

BayerBayer companyCompany Lampit,Lampit, Nifurtimox Nifurtimox pediatric pediatric (dosing (dosing in in children) children) PhasePhase III III MedicineMedicine DNDi, Antwerp Uni, Epichem, Celgene DNDi, Antwerp Uni, Epichem, Development of treatments Lead optimization Medicine Celgene Monash Uni Development of treatments Lead optimization Medicine Monash Uni GHIT, DNDi Screening program Hit identification Medicine Daiichi Sankyo GHIT, DNDi Screening program Hit identification Medicine Daiichi Sankyo DNDi Screening program (Natural Products Library) Hit identification Medicine DNDi Screening program (Natural Products Library) Hit identification Medicine DNDi, GHIT E1224 Phase II Medicine DNDi, GHIT E1224 Phase II Medicine DNDi, GHIT (Shionogi, DNDi, GHIT, (Shionogi, NTD Drug Discovery Booster (DDB-Chagas) Lead generation Medicine Takeda, AstraZeneca, GHIT) NTD Drug Discovery Booster (DDB-Chagas) Lead generation Medicine Takeda, AstraZeneca, GHIT) Drug discovery Eisai Broad Inst., GHIT Focused compound library screening Drug discovery Medicine Broad Inst., GHIT Focused compound library screening (optimization) Medicine Eisai (optimization) SVI, Baylor College, Aeras, Adjuvant to support vaccine development: SVI, Baylor College, Aeras, Adjuvant to support vaccine development: Preclinical Vaccine GHIT Chagas vaccine with SVI Preclinical Vaccine GHIT Chagas vaccine with SVI Adjuvant to support vaccine development: Fiocruz, GHIT Preclinical Vaccine ChagasAdjuvant vaccine to support with Fiocruzvaccine development: Fiocruz, GHIT Preclinical Vaccine Chagas vaccine with Fiocruz Dundee Uni Lead optimization project Lead optimization Medicine Dundee Uni Lead optimization project Lead optimization Medicine Wellcome Lead optimization III for Chagas disease Lead optimization Medicine Wellcome Lead optimization III for Chagas disease Lead optimization Medicine Wellcome/Dundee Uni Lead identification Medicine Wellcome/Dundee(Drug Discovery Unit) Uni HitHit to to lead Lead identification identification Wellcome & Dundee Lead identification Medicine GlaxoSmithKline (Drug Discovery Unit) Uni (Drug Discovery Unit) Wellcome Hit to lead identification Lead identification Medicine GlaxoSmithKline Wellcome Hit to Lead identification Wellcome Lead identification Medicine Develop novel therapies to prevent and treat TCOLF, Calibr Develop novel therapies to prevent and treat Discovery Medicine TCOLF, Calibr Chagas & leishmaniasis Discovery Medicine Chagas & leishmaniasis Mode of action and target identification of TCOLF, LSHTM Discovery (tool) Medicine Merck DNDi, Swiss TPH anti-ChagasicConcept generation compounds hit finding Basic research Medicine

Targeted screening and hit structure–activity MSD DNDiTCOLF, Georgia Uni Rapid selection of in vivo active anti- DiscoveryLead identification MedicineMedicine Trypanosomarelationship (SAR)cruzi compounds development Chagas disease project 1: developing safe company Identify new molecules using high throughput Drug discovery Medicine treatment for Chagas disease Janssen (J&J) GHIT, DNDi screening of molecular libraries and genotypic Discovery Medicine Novartis targets using CRISPR Cas9 technologies Chagas disease project 2: developing safe company Drug discovery Medicine treatment for Chagas disease Merck DNDi, Swiss TPH Concept generation hit finding Basic research Medicine CDIPD (UCSD), WIPO Pfizer PDE5 inhibitors Drug discovery Medicine Re:SearchDNDi In vivo POC Discovery Medicine MSD Targeted screening and hit structure–activity CONICETDNDi Compound screening LeadLead identification optimization MedicineMedicine relationship (SAR) development Sanofi DNDi Focused compound library screening Lead generation Medicine Novartis Wellcome Developing safe treatment for Chagas disease Drug discovery Medicine Shionogi GHIT, DNDi NTD Drug Discovery Booster Drug discovery Medicine Sanofi DNDi Focused compound library screening Lead generation Medicine Drug discovery DNDi, GHIT Compound screening Medicine Shionogi GHIT, DNDi NTD Drug Discovery Booster Drug(lead discovery generation) Medicine Takeda DrugDrug discovery discovery DNDi,DNDi, GHITGHIT CompoundNTD Drug Discoveryscreening Booster MedicineMedicine (lead(lead generation) generation) Takeda Drug discovery DNDi, GHIT NTD Drug Discovery Booster Medicine Total R&D projects for American trypanosomiasis (Chagas disease): 27 (lead generation)

Total R&D projects for American trypanosomiasis (Chagas disease): 28 21 CHIKUNGUNYA

DISEASE IMPACT19,20

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.

KEY FACTS21, 22

• In 2016, about 31,000 cases were reported to the Pan American Health Organization. • People 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. • Symptoms 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 PROJECTS

COMPANY PARTNERS PROJECT PHASE TYPE

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/ 21 https://www.cdc.gov/chikungunya/symptoms/ 20 http://www.who.int/mediacentre/factsheets/fs327/en/ 22 http://www.who.int/mediacentre/factsheets/fs327/en/

22 CURRENT R&D PROJECTS

COMPANY PARTNERS PROJECT PHASE TYPE

Compound screening, preclinical support, AbbVie DNDi Lead identification Medicine technical consulting

Discovery of anti-protozoan parasite drugs for Astellas AIST Discovery Medicine Trypanosoma cruzi

Focused compound library screening at Swiss AstraZeneca DNDi Lead identification Medicine TPH, Inst. Pasteur K

Bayer company Lampit, Nifurtimox pediatric (dosing in children) Phase III Medicine

DNDi, Antwerp Uni, Epichem, Celgene Development of treatments Lead optimization Medicine Monash Uni

GHIT, DNDi Screening program Hit identification Medicine Daiichi Sankyo DNDi Screening program (Natural Products Library) Hit identification Medicine

DNDi, GHIT E1224 Phase II Medicine

DNDi, GHIT, (Shionogi, NTD Drug Discovery Booster (DDB-Chagas) Lead generation Medicine Takeda, AstraZeneca, GHIT)

Drug discovery Broad Inst., GHIT Focused compound library screening Medicine Eisai (optimization)

SVI, Baylor College, Aeras, Adjuvant to support vaccine development: Preclinical Vaccine GHIT Chagas vaccine with SVI

Adjuvant to support vaccine development: Fiocruz, GHIT Preclinical Vaccine Chagas vaccine with Fiocruz

Dundee Uni Lead optimization project Lead optimization Medicine

Wellcome Lead optimization III for Chagas disease Lead optimization Medicine

Wellcome/Dundee Uni Hit to Lead identification Wellcome & Dundee Lead identification Medicine GlaxoSmithKline (Drug Discovery Unit) Uni (Drug Discovery Unit)

Wellcome Hit to Lead identification Wellcome Lead identification Medicine

Develop novel therapies to prevent and treat TCOLF, Calibr Discovery Medicine Chagas & leishmaniasis

Merck DNDi, Swiss TPH Concept generation hit finding Basic research Medicine

Targeted screening and hit structure–activity MSD DNDi Lead identification Medicine relationship (SAR) development

Chagas disease project 1: developing safe company Drug discovery Medicine treatment for Chagas disease Novartis Chagas disease project 2: developing safe company Drug discovery Medicine treatment for Chagas disease

CDIPD (UCSD), WIPO Pfizer PDE5 inhibitors Drug discovery Medicine Re:Search

CONICET Compound screening Lead optimization Medicine Sanofi DNDi Focused compound library screening Lead generation Medicine

Shionogi GHIT, DNDi NTD Drug Discovery Booster Drug discovery Medicine

Drug discovery DNDi, GHIT Compound screening Medicine (lead generation) Takeda Drug discovery DNDi, GHIT NTD Drug Discovery Booster Medicine (lead generation)

Total R&D projects for American trypanosomiasis (Chagas disease): 27

23 DENGUE Dengue hemorrhagic fever

DISEASE IMPACT23

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.

KEY FACTS24

• 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 PROJECTS

COMPANY PARTNERS PROJECT PHASE TYPE COMPANY PARTNERS PROJECT PHASE TYPE Compound screening, preclinical support, AbbVie DNDi Lead identification Medicine technical consulting

Discovery of anti-protozoan parasite drugs for Astellas AIST Discovery Medicine Celgene A-WOL (Wolbachia), NEB CompoundTrypanosoma screening cruzi Screening Medicine Focused compound library screening at Swiss AstraZeneca DNDi Lead identification Medicine TPH, Inst. Pasteur K

Bayer company DengueLampit, Nifurtimoxpurified and pediatric inactivated (dosing virus in children) Phase IIII Medicine WRAIR, Fiocruz Vaccine vaccine candidate (WRAIR antigens) DNDi, Antwerp Uni, Epichem, Celgene Development of treatments Lead optimization Medicine Monash Uni

GHIT, DNDi Screening program Hit identification Medicine Preclinical Daiichi Sankyo Dengue purified and inactivated virus GlaxoSmithKline WRAIR, Fiocruz (GlaxoSmithKline Vaccine DNDi Screeningvaccine candidate program (Natural Products Library) Hit identification Medicine antigens) DNDi, GHIT E1224 Phase II Medicine

DNDi, GHIT, (Shionogi, NTD Drug Discovery Booster (DDB-Chagas) Lead generation Medicine Takeda, AstraZeneca, GHIT) Late state WRAIR, Fiocruz Dengue therapeutic antibody Vaccine Drugpreclinical discovery Broad Inst., GHIT Focused compound library screening Medicine Eisai (optimization)

SVI, Baylor College, Aeras, Adjuvant to support vaccine development: Preclinical Vaccine GHIT Chagas vaccine with SVI Janssen (J&J) Wellcome, KU Leuven Discovery new anti-viral small molecules Discovery Medicine Adjuvant to support vaccine development: Fiocruz, GHIT Preclinical Vaccine Chagas vaccine with Fiocruz

Dundee Uni Lead optimization project Lead optimization Medicine Company Tetravalent subunit Phase I Vaccine Wellcome Lead optimization III for Chagas disease Lead optimization Medicine

Wellcome/Dundee Uni Hit to Lead identification Wellcome & Dundee Lead identification Medicine GlaxoSmithKline (Drug Discovery Unit) Uni (Drug Discovery Unit) Late stage MSD NIAID Tetravalent live attenuated Vaccine Wellcome Hit to Lead identification Wellcome Leadpreclinical identification Medicine

Develop novel therapies to prevent and treat TCOLF, Calibr Discovery Medicine Chagas & leishmaniasis

Merck DNDi,USAMRIID Swiss TPH ConceptTarget compound generation hit finding BasicLead identificationresearch MedicineMedicine

Targeted screening and hit structure–activity MSD DNDi Lead identification Medicine relationship (SAR) development

Novartis Company ChagasDiscovering disease new project anti-viral 1: developing treatments safe Drug discovery Medicine company Drug discovery Medicine treatment for Chagas disease Novartis Chagas disease project 2: developing safe company Drug discovery Medicine treatment for Chagas disease Phase III Sanofi Company Tetravalent live attenuated chimeric vaccine Vaccine CDIPD (UCSD), WIPO (efficacy completed) Pfizer PDE5 inhibitors Drug discovery Medicine Re:Search

CONICET Compound screening Lead optimization Medicine Sanofi Shionogi Hokkaido University Discovering new anti-viral treatment Drug discovery Medicine DNDi Focused compound library screening Lead generation Medicine

Shionogi GHIT, DNDi NTD Drug Discovery Booster Drug discovery Medicine

Four-strain recombinant viral vaccine Drug discovery Takeda DNDi,Company GHIT Compound screening Phase III VaccineMedicine (TAK003) (lead generation) Takeda Drug discovery DNDi, GHIT NTD Drug Discovery Booster Medicine (lead generation)

Total R&D projects for Americandengue/dengue trypanosomiasis hemorrhagic (Chagas fever: disease):12 27

25 HUMAN AFRICAN TRYPANOSOMIASIS Sleeping sickness

DISEASE IMPACT25

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-to- child 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.

KEY FACTS26, 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/ 27 http://www.who.int/mediacentre/factsheets/fs259/en/ 26 http://www.who.int/trypanosomiasis_african/disease/en/

26 CURRENT R&D PROJECTS

COMPANY PARTNERS PROJECT PHASE TYPE

Compound screening, preclinical support, AbbVieCOMPANY DNDiPARTNERS PROJECT LeadPHASE identification TYPEMedicine technical consulting

Discovery of anti-protozoan parasite drugs for Astellas AIST Discovery Medicine Trypanosoma cruzi

Focused compound library screening at Swiss AstraZeneca DNDi Compound screening ScreeningLead identification MedicineMedicine AbbVie TPH, Inst. Pasteur K

Bayer company Lampit, Nifurtimox pediatric (dosing in children) Phase III Medicine

DNDi, Antwerp Uni, Epichem, Celgene Development of treatments Lead optimization Medicine DNDi,Monash Antwerp Uni Uni, Epichem, Celgene Development of treatments Lead optimization Medicine Monash Uni GHIT, DNDi Screening program Hit identification Medicine Daiichi Sankyo DNDi Screening program (Natural Products Library) Hit identification Medicine

DNDi, GHIT E1224 Phase II Medicine

DNDi,TCOLF GHIT, (Shionogi, Drug discovery Discovery Medicine NTD Drug Discovery Booster (DDB-Chagas) Lead generation Medicine Takeda, AstraZeneca, GHIT)

Drug discovery Broad Inst., GHIT Focused compound library screening Medicine Eisai (optimization)

SVI, Baylor College, Aeras, AdjuvantT. brucei drugto support discovery: vaccine ADMET development: and PK TCOLF, NEU, CSIC PreclinicalLead optimization MedicineVaccine GlaxoSmithKline GHIT Chagassupport vaccinefor hit-to-lead with SVI optimization

Adjuvant to support vaccine development: Fiocruz, GHIT Preclinical Vaccine Chagas vaccine with Fiocruz

Dundee Uni Lead optimization project Lead optimization Medicine Hit to lead optimization for kinetoplastid WellcomeTCOLF, Monash Uni Lead optimization III for Chagas disease LeadDiscovery optimization MedicineMedicine diseases: single agents for Chagas and HAT Wellcome/Dundee Uni Hit to Lead identification Wellcome & Dundee Lead identification Medicine GlaxoSmithKline (Drug Discovery Unit) Uni (Drug Discovery Unit)

Wellcome Hit to Lead identification Wellcome Lead identification Medicine

Develop novel therapies to prevent and treat Merck TCOLF,DNDi, Swiss Calibr TPH Concept generation hit finding DiscoveryBasic research MedicineMedicine Chagas & leishmaniasis

Merck DNDi, Swiss TPH Concept generation hit finding Basic research Medicine

Targeted screening and hit structure–activity MSD DNDi Lead identification Medicine relationship (SAR) development Drug discovery Novartis Wellcome Discovering (D) new affordable and Medicine Chagasadaptable disease NCEs project 1: developing safe (lead optimization) company Drug discovery Medicine treatment for Chagas disease Novartis Chagas disease project 2: developing safe company Drug discovery Medicine treatment for Chagas disease

CDIPD (UCSD), WIPO PfizerSanofi DNDi PDE5Fexinidazole inhibitors (antiprotozoal compound) DrugPhase discovery II / III MedicineMedicine Re:Search

CONICET Compound screening Lead optimization Medicine Sanofi DNDi Focused compound library screening Lead generation Medicine

ShionogiTakeda GHIT,DNDi, DNDiGHIT NTDCompound Drug Discovery screening Booster DrugLead identificationdiscovery MedicineMedicine

Drug discovery DNDi, GHIT Compound screening Medicine (lead generation) Takeda Drug discovery DNDi, GHIT NTD Drug Discovery Booster Medicine (lead generation) Total R&D projects for Human African trypanosomiasis (sleeping sickness): 9 Total R&D projects for American trypanosomiasis (Chagas disease): 27

27 LEISHMANIASIS

DISEASE IMPACT28,29

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.

KEY FACTS30, 31

• An 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. • Over 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/ 30 http://www.dndi.org/diseases-projects/leishmaniasis/ 29 http://www.who.int/mediacentre/factsheets/fs375/en/ 31 http://www.who.int/mediacentre/factsheets/fs375/en/

28 CURRENT R&D PROJECTS

COMPANY PARTNERS PROJECT PHASE TYPE

Compound screening, preclinical support, AbbVie DNDi Discovery Medicine technical consulting

Focused compound library screening at Inst. AstraZeneca DNDi Lead identification Medicine Pasteur K, Dundee Uni, Swiss TPH

Celgene LSHTM, DNDi Development of treatments Lead optimization Medicine

GHIT, DNDi Screening program Hit identification Medicine

Daiichi Sankyo Screening program DNDi Hit identification Medicine (Natural Products Library)

DNDi, GHIT NTD Drug Discovery Booster (DDB- Eisai Lead generation Medicine (Shionogi, Takeda, AstraZeneca) Leishmaniasis)

Wellcome/ Dundee Uni (Drug Lead identification Medicine Discovery Unit) Hit to lead identification

Wellcome Hit to lead identification Lead identification Medicine

Develop novel therapies to prevent and treat TCOLF, Calibr Discovery Medicine Chagas & leishmaniasis GlaxoSmithKline Wellcome/ Dundee Uni Lead optimization I for visceral leishmaniasis Lead optimization Medicine (Drug Discovery Unit)

Wellcome/ Dundee Uni Lead optimization II for visceral leishmaniasis Lead optimization Medicine (Drug Discovery Unit)

TCOLF, Uni Leon, CBMSO In-vitro screening for treating leishmaniasis Discovery Medicine

Merck DNDi, Swiss TPH Concept generation hit finding Basic research Medicine

Target screening and hit structure–activity MSD DNDi Lead identification Medicine relationship (SAR) development

Leishmaniasis project: discovering a superior Novartis Wellcome Drug discovery Medicine treatment

DNDi Focused compound library screening Lead generation Medicine Sanofi DNDi Compound screening Lead identification Medicine

Shionogi GHIT, DNDi NTD Drug Discovery Booster Drug discovery Medicine

Drug discovery (lead DNDi, GHIT Compound screening Medicine generation)

Drug discovery (lead Takeda DNDi, GHIT NTD Drug Discovery Booster Medicine generation)

Lead optimization of the aminopyrazole series Drug discovery (lead DNDi, GHIT Medicine for visceral leishmaniasis optimization)

Total R&D projects for leishmaniasis: 21

29 LYMPHATIC FILARIASIS

DISEASE IMPACT32

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.

KEY FACTS33

• An 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 PROJECTS

COMPANY PARTNERS PROJECT PHASE TYPE

Collaborative preclinical development LSTM Discovery Medicine program

AbbVie

DNDi Compound screening Lead identification Medicine

Focused compound library screening and AstraZeneca A-WOL, LSTM Lead identification Medicine DMPK support

Monclair State Uni, DNDi, Development of treatments Lead optimization Medicine NPIMR, Bonn Uni

Celgene

A-WOL (Wolbachia), NEB Compound screening Screening Medicine

UCSD, UCSF, LSTM, Bonn Uni, AbbVie, Anacor, Johnson & Development of Macrofilaricide Drug Lead identification Medicine Johnson, Eisai, Merck, Calibr, Accerelator (MacDA) DNDi, BMGF

Eisai Post-approval Development of diethylcarbamazine citrate surveillance (stability Company Medicine (DEC) study for shelf-life extension)

LSTM, Liv Uni, GHIT Novel compounds for anti-Wolbachia Lead optimization Medicine

Merck DNDi, NPIMR Concept generation hit finding Basic research Medicine

DNDi Target compound screening Lead identification Medicine

MSD

In vivo POC studies macrofilaricide DNDi Discovery Medicine drug accelerator

Sanofi DNDi Focused compound library screening Lead generation Medicine

Total R&D projects for lymphatic filariasis: 12

31 MYCETOMA

DISEASE IMPACT34,35

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.

KEY FACTS36, 37

• Mycetoma commonly affects young adults, particularly males aged between 20 and 40 years. • Actinomycetoma 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. • Approximately 40% of Mycetoma cases worldwide are Eumycotic. • Causative 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 PROJECTS

COMPANY PARTNERS PROJECT PHASE TYPE

Eisai DNDi E1224 Clinical (preparation for phase II) Medicine

Total R&D projects for mycetoma: 1

34 http://www.who.int/buruli/mycetoma/en/ 36 http://www.who.int/buruli/mycetoma/en/ 35 http://www.dndi.org/diseases-projects/mycetoma/ 37 http://www.dndi.org/diseases-projects/mycetoma/

32 CURRENT R&D PROJECTS