SUPPORTING RESEARCH IN NEGLECTED TROPICAL Lessons from AbbVie’s Neglected Diseases Initiative

Jane Nelson SUPPORTING RESEARCH in NEGLECTED TROPICAL DISEASES Lessons from AbbVie’s Neglected Diseases Initiative

Written by Jane Nelson Designed by Alison Beanland Cover photographs: 1. MAP International program in Bolivia/MAP International 2. Scientists at AbbVie working on the Neglected Diseases Initiative/AbbVie 3. Swiss Group Photo Contest/Anne Jennings 4. / National Institute of and Infectious Diseases (NIAID) © 2016 by the CR Initiative at the Harvard Kennedy School SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES Lessons from AbbVie’s Neglected Diseases Initiative

Executive Summary 5

I. The need for collective action on Neglected Tropical Diseases 7

II. AbbVie’s engagement in tackling NTDs 9

1. Harnessing the company’s institutional and scientific capacity 10 1.1 The Executive Committee for Neglected Diseases (ECND) 10 1.2 Leveraging the company’s scientific expertise and infrastructure 11 1.3 Supporting innovative agreements for product development partnerships 11 1.4 Aligning with the company’s Corporate Responsibility strategy 12

2. Leveraging the skills and commitment of individual scientists 13

3. Engaging in cross-sector product development partnerships 16 3.1 Drugs for Neglected Diseases initiative (DNDi) 18 3.2 Medicines for Malaria Venture (MMV) 20 3.3 The TB Alliance and TB Drug Accelerator (TBDA) 22 3.4 The Anti- Consortium (A-WOL) and Macrofilaricidal Drug Accelerator (MacDA) 24

4. Supporting the education of future scientists and leaders 26

5. Funding projects and dialogues 27 5.1 MAP International in Côte D’Ivoire and Bolivia 27 5.2 The Sabin Institute in 28 5.3 Convening officials and academics 29

6. Participating in multi-stakeholder policy and advocacy platforms 29 6.1 The CEO Roundtable 29 6.2 The London Declaration on Neglected Tropical Diseases 30

III. Conclusion and lessons learned 31

Methodology and Acknowledgements 34

Endnotes 34 Neglected Tropical Diseases afflict about one billion of the world's poorest people. Yet these diseases are largely treatable. Moreover, controlling them offers a powerful strategy for tackling many of the conditions that promote . We need to scale up action against these diseases and eradicate the ones we can. Ban Ki-moon Secretary-General1

4 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE Executive Summary

Neglected Tropical Diseases (NTDs) undermine the physical and cognitive health and the economic opportunity of more than one billion people, most of them among the world’s poorest and least able to access or advocate for solutions.

The burden of Neglected Tropical Diseases From a research and development (R&D) perspective, one Neglected Tropical Diseases (NTDs) undermine the physical of the most encouraging institutional innovations in global and cognitive health and the economic opportunity of more health over the past 15 years has been the emergence than one billion people, most of them among the world’s of independent, nonprofit, often multi-stakeholder drug poorest and least able to access or advocate for solutions. research organizations and alliances. These are facilitating As Hotez et al commented in a 2009 edition of The Lancet, new models of product development partnerships (PDPs) “People in the bottom billion are the poorest in the world; between companies, public, private and philanthropic they are often subsistence farmers, who essentially live on donors, regulators, research institutes and universities, and no money and are stuck in a poverty trap of , conflict governments and community organizations in and no education. One of the most potent reinforcements countries. of the poverty trap is the neglected tropical diseases. Almost everyone in the bottom billion has at least one of The role of corporate engagement these diseases.”2 The emergence of these new types of PDPs has been accompanied by new models of corporate social Although encouraging progress has been made in recent responsibility and shared value creation by some of decades, the prevention, control, elimination and eradication the world’s leading pharmaceutical and biotechnology of these diseases remain one of the great public health companies. equity challenges of our generation. And given the impact of NTDs more broadly on nutrition, education, economic In some cases, companies are undertaking their own R&D productivity, community resilience and health systems in-house and/or exploring new licensing or pricing models capacity, these efforts are also crucial to ending extreme for existing drugs and interventions. In others, they are poverty. supporting long-term product donations, capacity building and corporate philanthropy initiatives. And a number of The need for new models of partnership them are enabling some of their top scientists to volunteer As outlined in Part I of this report, a key imperative in their skills, time and assets to share compounds for addressing the challenge is how to align the necessary screening, provide technical expertise, and offer pro-bono scientific expertise, assets and financial resources needed program enhancement support to non-profit research to discover and develop drugs to prevent or treat these partners. diseases. Global pharmaceutical and biotechnology companies have many of these capabilities, but with few None of these activities are easy or short-term in . exceptions, they have little or no commercial rationale to They require support and a long-term commitment by invest in many years of research and development (R&D) to corporate executives, as well as strong leadership and bring such drugs to market. And even then, the drugs would dedication by the scientists who engage. They require the still need to be made affordable, accessible and reliable for ability to build internal coalitions within the company, both extremely poor often living in remote rural areas, between different R&D teams and between these teams and urban and conflict zones. colleagues in corporate responsibility, legal departments, public affairs, and the corporate foundation. And they require As such, sustained efforts to discover, develop and deliver the ability to build non-traditional external partnerships treatments for NTDs are simply not possible without new and alliances, including with competitors, as well as with models of cooperation between public, private and nonprofit non-profit research organizations, donors, universities and organizations. governments.

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 5 The case of AbbVie Engagement between AbbVie’s scientists and several This case study focuses on AbbVie, a global, research-based 3key product development partnerships (PDPs), often biopharmaceutical company formed in 2013 following alongside peers from other companies. The case focuses on separation from Abbott Laboratories. The company's AbbVie’s engagement with the Drugs for Neglected Diseases mission is to use its expertise, dedicated people and unique initiative (DNDi), Medicines for Malaria Venture (MMV), approach to innovation to develop and market advanced TB Alliance, TB Drug Accelerator, Anti-Wolbachia Consortium therapies that address some of the world's most complex (A-WOL), and Macrofilaricidal Drug Accelerator (MacDA). and serious diseases. AbbVie employs more than 28,000 people worldwide and markets medicines in more than AbbVie’s support for a student summer internship 170 countries. 4program, through the Franciscan Institute for World Health, which aims to develop future scientific and AbbVie’s engagement with some of the key nonprofit leadership skills. initiatives tackling NTDs is illustrative of the types of institutional, individual and collective leadership that Examples of the AbbVie Foundation’s philanthropic are needed to support effective product development 5support for community-based delivery, capacity building partnerships as well as public advocacy and awareness- and evaluation programs led by MAP International and the raising in this field. Although AbbVie has no existing products in parts of and Latin America. or any commercial interest in discovering/developing drugs for NTDs, its senior management and scientists are The company’s participation in some of the broader committed to partnering with other organizations to help 6multi-stakeholder platforms that have emerged to them to undertake such research and to implement other raise public awareness, support public advocacy, mobilize initiatives to tackle NTDs. Part II of the report looks at: resources, and share knowledge. These include initiatives such as the Gates Foundation’s Health CEO Roundtable, The work of the company’s Executive Council for United Against NTDs, and the London Declaration Against 1Neglected Diseases (ECND), with a focus on the roles NTDs. of AbbVie’s R&D, technology licensing and collaborations, corporate responsibility, government affairs, and philanthropic Part III of the report concludes with reflections on some foundation teams. Coordination across these different parts of the key lessons learned. It draws on these to offer of the company has been essential in enabling it to develop recommendations on how companies can continue to play a innovative external partnerships. leadership role, in partnership with others, to promote global public health and the Sustainable Development Goals (SDGs) The leadership role being played by individual more broadly. The SDGs are a set of 17 goals to end poverty, 2scientists to turn an institutional commitment into fight inequality and injustice, and tackle and action. It focuses on Dr. Dale Kempf, one of Abbvie’s environmental degradation by 2030. They were adopted Distinguished Research Fellows, Dr. Kennan Marsh, by more than 190 world leaders at the United Nations AbbVie’s Director of Experimental Sciences and Senior Sustainable Development Summit on 25 September 2015 as Research Fellow, Development Science, and Dr. Tom von a core part of the 2030 Agenda for Sustainable Development.3 Geldern, one of several retirees working with his former SDG Goal #3: “To ensure healthy lives and provide well- colleagues on these initiatives. being for all”, is the most directly relevant in the fight against Neglected Tropical Diseases, although these diseases also have an impact on the achievement of several other goals.

6 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE I The need for collective action on Neglected Tropical Diseases

Neglected Tropical Diseases (NTDs) are “…a group of parasitic and bacterial diseases that cause substantial illness for more than one billion people globally.“

Affecting the world’s poorest people, NTDs impair physical status in public health priorities. Lack of reliable statistics and cognitive development, contribute to and and unpronounceable names of diseases have all hampered child illness and , make it difficult to farm or earn a efforts to bring them out of the shadows.”5 And in turn, living, and limit productivity in the workplace. As a result, these characteristics make such diseases a low priority for NTDs trap the poor in a and disease.”4 commercial pharmaceutical research and development (R&D). They represent a major humanitarian challenge and priority for improving equity, as well as an economic NTDs also provide an excellent example of the complex and development challenge. inter-relationships between the different Sustainable Development Goals (SDGs). As Peter Hotez, President of The World Health Organisation (WHO) has prioritized 17 The Sabin Institute, and Neeraj Mistry, Managing Director NTDs, which are endemic in 149 countries affecting some of the Global Network for Neglected Tropical Diseases 1.4 billion people, and set targets for their prevention, have commented, “… we need to consider the overlap control, elimination and eradication. The task is a complex between NTDs and other factors: nutrition; water, , and challenging one. As WHO points out, “The people who and ; maternal and child health; and education. are most affected by these diseases are often the poorest Development goals cannot be achieved in . In fact, populations, living in remote, rural areas, urban slums or NTDs are so inextricably linked to these development issues conflict zones. …Lacking a strong political voice, people that their prevalence is seen as an effective proxy for broader affected by these tropical diseases have a low profile and socioeconomic and development.”7

Diagram 1 The 17 Priority NTDs identified by the World Health Organization in 20106

VIRUSES HELMINTH Rabies Dengue & -worm Foodborne trematodiases Human African BACTERIA Lymphatic Trypanosomiasis Soil-transmitted Buruli Ulcer River Blindness

Source: Rachel Cotton, Phd. student in , Harvard University. Neglected Tropical Diseases: Challenges for the Post-2015 Development Era. Public Library of Science (PLOS) Blogs: Student Blogs.

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 7 I THE NEED FOR COLLECTIVE ACTION ON NEGLECTED TROPICAL DISEASES

As a result, efforts to prevent, control, eliminate or eradicate organizations in a time-bound, public commitment to NTDs require a combination of scientific innovation, social and eradicate, eliminate or control ten of these NTDs by 2020. economic interventions, policy support, and new financing And in September 2015, more than 190 Member States of mechanisms. They rely on the discovery, development the United Nations approved the Sustainable Development and delivery of drugs and therapeutic treatments, where Goals, with NTDs addressed in SDG#3 “Promoting Health and there are few commercial incentives for R&D, alongside Wellness”, as part of the following target: “By 2030 end the concerted efforts to strengthen health systems and address of AIDS, tuberculosis, malaria, and neglected tropical broader environmental health issues such as unsafe water diseases and combat , water-borne diseases, and other and sanitation. To be successful in these efforts there is a communicable diseases.” crucial need for leadership at the institutional, individual and collective level. In particular, there is the need for: In all these initiatives, there has been an increased focus on the role of pharmaceutical and biotechnology companies • Strong institutional support from individual governments, as partners in tackling NTDs. Depending on the company companies, international agencies, academic and research and NTD being addressed, roles can range from developing institutions, and foundations; and delivering commercially viable drugs to leveraging the scientific and technical skills of employees, making product • Outstanding individual leadership from a wide range of donations, and providing philanthropic or advocacy support people from research scientists and senior policy makers, to partner organizations. public health officials and leaders in business and civil society to community healthcare workers; and The discovery and development of new drugs is particularly challenging. As the diagram below illustrates, getting to the • More collaborative approaches to problem-solving and new point of regulatory approval usually takes about 14 to 16 years. models of partnership between governments, civil society Of every 5,000 to 10,000 new compounds synthesized in the and the corporate sector. These range from project-based discovery phase of the process, about 250 enter preclinical and product development partnerships to multi-stakeholder testing, five enter clinical testing, and one gets approved collective action bringing together a large number of by regulators. In the case of NTDs, the long time horizons different actors at global and national levels. and low conversion rates are exacerbated by the lack of commercial incentives given that the people most affected by Collaborative action to tackle NTDs has gained considerable NTDs are amongst the world’s poorest. It is for these reasons momentum over the past decade. In 2009, building on lessons that innovative product development partnerships, which from earlier product development partnerships, the Bill & bring together public, private and philanthropic funders and Melinda Gates Foundation convened its first CEO Roundtable scientists play such a vital role in discovering and developing to encourage pharmaceutical companies to work with the drugs to tackle NTDs. foundation and research NGOs to tackle NTDs. In 2012, WHO published a Roadmap for the control, elimination and The following profile of AbbVie outlines examples of eradication of 17 NTDs by 2020, which built on a decade of leadership within the company as well as its engagement dialogue and lessons learned. In January 2012, the London in external product development partnerships, community Declaration on Neglected Tropical Diseases brought together projects and alliances aimed at addressing NTDs. a group of governments, companies, funders and research

Diagram 2 Typical timeline for drug R&D to regulatory approval

DRUG R&D CLINICAL TRIALS

20-100 people 100-300 people 1,000-3,000 people 1-2 years 1-2 years 1-2 years 1 year 1-2 years 1-2 years 1-2 years 1-2 years Target Hit Lead Pre-Clinical Phase 1: Phase 2: Phase 3: FDA Review identification Generation Generation & Animal Studies Safety Efficacy Safety Efficacy Safety & Approval & Validation Optimization

Source: Adapted by the author from a diagram provided by AbbVie.

8 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II AbbVie’s engagement in tackling NTDs

“We are proud to support our top scientists in their pro-bono research efforts to find treatments and for a number of tropical diseases. Our support of these efforts is not driven by commercial interests but by a recognition that our science and scientists can contribute to the discovery and development of needed medicines. Working with research partners such as DNDi, Gates Foundation’s TBDA, MMV and some industry peers, I am confident that we can and will have a positive impact in turning the tide against many of these devastating diseases.” Jim Sullivan, Vice President, Discovery, Global Pharmaceutical R&D, AbbVie

AbbVie combines the scientific expertise and long-standing contribution to the global effort against NTDs by contributing corporate legacy of an established global pharmaceutical their time, expertise, and equipment to nonprofit product company with the focus, innovative culture and capability development partnerships that are doing research in this of a leading biotech. That has given AbbVie the unusual area. opportunity to combine its proven scientific expertise and long-standing corporate responsibility legacy with a ‘new’ AbbVie first engaged in global efforts to tackle NTDs in 2009, company mindset and efforts to build its own corporate when part of Abbott. In 2009, the Bill and Melinda Gates culture, business identity and commercial success in the Foundation (BMGF) convened its first CEO Roundtable to global marketplace. The company’s commercial discovery encourage pharmaceutical companies to work alongside the and development efforts focus on therapeutic areas where it foundation and some of the nonprofit research organizations has proven expertise including in the areas of immunology, it was supporting to scale up and coordinate awareness, oncology, and neurology among others. funding and R&D efforts in tackling NTDs. Concurrent with the meeting of pharmaceutical CEOs, top scientists from More than 6,000 scientists from diverse backgrounds and some of the participating companies met their counterparts disciplines work in the research and development laboratories in several of these research-based nonprofits. This dialogue of AbbVie. Most are based in the company’s headquarters was the basis for building personal relationships, in North Chicago, many thousands of miles away from the strengthening mutual respect and trust, and identifying remote rural communities and urban slums in Africa, specific ideas for cooperation between the participating and Latin America, where an estimated 1.4 billion people companies and nonprofit organizations. Shortly afterwards, suffer from debilitating neglected tropical diseases. There the company established an internal, multi-disciplinary group is little commercial rationale for AbbVie to invest in the to address NTDs, called the Executive Council for Neglected challenging, long-term process of discovering, developing, Diseases (ECND). and manufacturing drugs to tackle these diseases. Yet, many of the company’s highly qualified scientists have the skills and When AbbVie separated from Abbott in 2013 AbbVie's technologies that could help to make a positive difference. CEO, Richard Gonzalez, supported the continuation of the And they share a deep-seated professional commitment to neglected diseases initiative. This included the continuation advancing scientific knowledge and improving human health. of the ECND, engagement in the BMGF CEO Roundtable and scientists' participation in external product development AbbVie has enabled more than 160 of its scientists to put partnerships. this commitment into action. Unlike a number of its peers in the healthcare sector, the company does not have a These decisions by senior management, provide a good commercial business focused on any of these diseases—and example of values-based leadership that draws directly on does not plan to develop one. However, some of its leading the company’s core scientific capabilities and assets to help scientists recognized they could make a meaningful pro bono address a global health challenge, but is not intended to

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 9 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

become a revenue-generating business for the company. 1.1 The Executive Council for Neglected Diseases (ECND) While the time and skills of the company’s scientists are being provided to their nonprofit partners on a pro bono ECND is a formal, permanent multi-disciplinary body that basis, the initiative is being managed with a similar level is co-lead by the company’s Global Pharmaceutical R&D of project management discipline and accountability, and department and its Corporate Responsibility department. is providing the same disciplines and quality of scientific Its mission is as follows: expertise and professional advice, that would be applied to a commercial venture. “In partnership with the public and private sectors, the Council will support the development or modification of Harnessing the company’s institutional new drugs to address unmet needs in areas of neglected 1and scientific capacity disease prevention, diagnosis, treatment, and management. In this pursuit the Council will leverage the company’s core The following examples illustrate how some of the company’s competencies and existing resources as identified through research and development (R&D) teams are working with intensive internal review.” other functions within the company to manage the cross- functional effort on tackling neglected diseases. They review The ECND identifies and collaborates with key stakeholders some of the activities being undertaken by the Executive and experts both within the company and externally, aiming Council for Neglected Diseases and the company's scientists to bring AbbVie resources to partners working in some of as well as the Technology Licensing & Collaborations team these underserved disease areas, which will be discussed in and the Corporate Responsibility team. more detail later in the case study. It is structured as follows:

Diagram 3 AbbVie’s Executive Council for Neglected Diseases The ECND is a cross-functional team comprised of leaders from across the business as follows: Distinguished and Senior Research Fellows Senior Project Leader, Infectious Diseases VP, Pharmaceutical R&D VP, Corporate Responsibility Vice President, Corporate Responsibility, Brand & Senior Director, Global Philanthropy Executive Council for Neglected Diseases (ECND) Senior Director, Global Government Affairs • Corporate Responsibility • Regulatory Affairs • AbbVie Foundation • Government Affairs Senior Director, Regulatory Business • Pharmaceutical R&D • Licensing & Acquisition Development Director, Technology Licensing & Collaborations NTD Discovery/Preclinical Team Director, AbbVie Foundation • Chemistry • Cheminformatics • PK/ADME • Pharmaceutics • Preclinical Safety • Preclinical Toxicology • Process Chemistry • High-throughput Screening

10 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

1.2 Leveraging the company’s scientific expertise • Process Chemistry: the Process Chemistry team is and infrastructure responsible for developing methods to manufacture large amounts (kilograms, metric tons, etc) of the new drug. As outlined in the following section, some of AbbVie’s The Process Chemistry team optimizes a cost efficient and most experienced scientists have played a crucial personal environmentally respectful synthesis of each compound. leadership role in establishing and building the company’s partnerships on NTDs. They have done so with the support Section 3 of this chapter illustrates the engagement of of company leaders, working within and being able to AbbVie’s scientists with the Drugs for Neglected Diseases leverage the management structures and processes, as well initiative (DNDi), Medicines for Malaria Venture (MMV), TB as the scientific and technological assets and infrastructure Alliance and TB Drug Accelerator, Anti-Wolbachia Consortium of the company. In addition to their time, the scientists who (A-WOL), and Macrofilaricidal Drug Accelerator (MacDA). are participating in the initiative are contributing a range of different scientific and technical skills, resources and research 1.3 Supporting innovative agreements for product equipment. development partnerships

The company tracks the time spent on these activities, and in One of the major challenges in developing new models 2014 and 2015, AbbVie scientists contributed 30,677 pro bono of partnership between nonprofit or public research hours, partnering externally with the product development organizations and commercial companies, where Intellectual partnerships profiled later in the case study. This represents a Property (IP) is a crucial element of successful business doubling of the time spent by the company’s scientists in models, is how to structure collaboration, licensing and the prior two year period. These scientists are drawn from other types of business development and legal agreements the following four teams within the company’s R&D group: that meet the public health goals of the nonprofit or public research partners, while also protecting IP and managing • Discovery: teams within the Discovery organization risks to the company. This has required AbbVie’s legal and identify targets against which potential therapies may transaction support teams as well as its scientists to think be directed. The teams synthesize new compounds, differently, to innovate, and to collaborate both internally characterize the activity against the target and catalog any and externally in non-traditional ways. potential off-target (toxic) activities of the compounds. In this iterative process, optimized compounds that have The role of the Technology Licensing & Collaborations (TLC) the right properties to be drugs are designed. team, for example, is to provide transaction support to AbbVie’s Research and Development, Medical Affairs and • Development Sciences: teams within Development Operations teams for their “everyday” licensing and business Sciences work to understand the behavior of compounds in needs. These transactions may include agreements for animals, with the goal to predict the characteristics of the confidential disclosures (CDAs), material transfers (MTAs), compounds in . Efforts focus largely on sponsored research collaborations, consortia, registries, (how the compound is broken down in the body), technology licenses, etc. pharmacokinetics (what and how often should a compound be given to be efficacious) and toxicology (how In the case of the company’s scientists providing pro bono safe is the compound; what are the potential ). support for external product development partnerships in the area of neglected diseases, the TLC team has leveraged its • Drug Product Development: the Drug Product professional expertise and time to provide broad transaction Development team is responsible for preparing a dosage support for all aspects of these external relationships, form (eg, capsule, tablet, solution) that will be used to including CDAs, MTAs and collaboration agreements. deliver the compound to the .

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 11 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

AbbVie’s approach to partnering in the NTD area has been The framework has three central pillars: to couple business development concepts to structuring • Improve health outcomes: Targeting unmet needs and relationships (for example a focus on mutually beneficial enhancing access to healthcare. agreements, good governance, publications, publicity, • Operate responsibly: Developing a corporate culture licenses, etc.) and aligning these with the objectives to and standards for responsible research, product quality deliver on the goals of advancing global public health and and safety, workplace practices, human rights and corporate responsibility. Again, this provides a good example environmental impacts. of leveraging the core capabilities of the company to support • Contribute to communities: Partnering with selected non-commercial initiatives that would not be possible in the communities in education and employee engagement. absence of these capabilities. The key elements of this corporate responsibility framework 1.4 Aligning with the company’s Corporate Responsibility are outlined in the diagram below. In addition to co-leading strategy the company’s Executive Council on Neglected Diseases, the Corporate Responsibility team provides the framework and Alongside the Global Pharmaceutical R&D group, the supports the pro bono work of AbbVie’s scientists. As outlined Neglected Diseases initiative is co-led by AbbVie’s Corporate in Section 5, The AbbVie Foundation, which is an independent Responsibility team. The company's corporate responsibility 501(c)(3) organization that serves as one of the pillars of AbbVie’s framework aligns with AbbVie’s core purpose, and leverages overall corporate responsibility strategy, is also providing the company’s expertise, philanthropy and collaborations. philanthropic support to select community-based initiatives focused on tackling NTDs. At AbbVie, it’s both what we do and how we do it that matters. We understand that addressing the world’s health challenges requires a comprehensive and responsible approach. That’s why AbbVie goes beyond medicine, not only Diagramdeveloping 4 innovative AbbVie’s therapies, Corporate but also using Responsibility our resources to improve Framework healthcare.

commitments

IMPROVE HEALTH OUTCOMES OPERATE RESPONSIBLY CONTRIBUTE TO COMMUNITIES

Target unmet needs to support patients and Cultivate an ethical, transparent & inclusive Partner with our communities to address enhance access to healthcare across geographies culture to drive sustainable growth challenges of the underserved

ethical responsible culture research

patient capacity transformative engaged support building education employees

quality & healthy safety environment

innovative medical stakeholder research education engagement sustainable great supply chain employer

core tactics

EXPERTISE PHILANTHROPY COLLABORATION

12 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

“It is very motivating for our scientists to get involved. Most came to the pharmaceutical sector because they want to use their science to impact peoples’ lives. To them the success of drug discovery is measured in patients’ lives saved or improved. Our Neglected Diseases program offers them an additional opportunity beyond their normal responsibilities.” Dr. Dale Kempf, Distinguished Research Fellow

Leveraging the skills and commitment of leading the type of preclinical studies that are crucial for 2individual scientists advancing compounds from the laboratory to clinical studies in humans. The effort to tackle Neglected Tropical Diseases calls for outstanding individual leadership that combines scientific, In 2009, when the Gates Foundation first convened the CEO technical and managerial skills with the ability to build Roundtable, Dr. Kempf was asked by senior management partnerships and a passionate commitment to the long to represent the company. As he engaged with his fellow and challenging process of improving health outcomes. scientists from other companies, and with the nonprofit The scientists who work inside large, research-based product development partnerships being supported by the companies like AbbVie are one group of individual leaders Gates Foundation, he recognized the opportunity for the who are playing an increasingly important role in the fight company, its scientists and their technological platforms to against these diseases. make a meaningful contribution, even though it had no commercial business focused on NTDs. This was the As outlined in the previous section, the senior management start of the Neglected Diseases initiative, which Dr. Kempf, of AbbVie has made a corporate-level commitment to Dr. Marsh and their colleagues have continued to build since support non-commercial, external product development the creation of AbbVie, taking it to a new level in terms of partnerships that are focused on tackling NTDs. This scope, scale and number of partnerships, with increasingly executive support and institutional platform have been robust project management and measurement. essential to enabling anything to happen. Yet, it is the skills, time and personal commitment of individual scientists that From the outset, Dr. Kempf and Dr. Marsh have played at are at the heart of making these relationships a success— least five crucial leadership roles in building the company’s both in terms of managing the day-to-day projects and Neglected Diseases initiative and inspiring many others to partnerships, and providing the type of world-class scientific get actively involved: expertise that is needed to discover and develop new drugs and treatments. It is also fair to say, that it has been • They have provided their own world-class scientific the personal passion and determination of some of the expertise and networks to AbbVie’s partner organizations, company’s top scientists that have underpinned AbbVie’s serving as technical experts and role models both initial engagement in tackling NTDs, and subsequently internally and externally. The brief biographies in Box 1 increasing the level of this commitment as more scientists provide an indication of their professional reputations and have joined the pro bono effort in recent years. success as research scientists. As Dr. Kempf comments, “… between Kennan and myself, we have over 60 years worth Two such leaders are Dr. Dale Kempf, one of the company’s of experience and a full understanding of what the drug Distinguished Research Fellows, a 30-year pharmaceutical discovery pathway looks like. We also have lots of contacts R&D veteran and co-inventor of AbbVie’s HIV/AIDS drugs, and networks, which we can tap into to support our who leads the initiative on neglected diseases, and his partners.”8 colleague Dr. Kennan Marsh, the company’s Director of Experimental Sciences and Senior Research Fellow, who • In addition to carrying out scientific work on behalf of brings more than 30 years of experience in conducting and partner organizations, they have also played a broader

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 13 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

“It is the scale of our technology platforms as well as our scientific expertise and our procedural and process expertise that enable us to make a meaningful contribution to our nonprofit partners. …We are able to help them ask the right questions and better understand what is happening with their integrated data. We are able to conduct assays and studies at a scale, scope and cost-effectiveness that our partners would not be able to do alone. Through these contributions, we can help them advance compounds from the laboratory to clinical studies in humans.” Dr. Kennan Marsh, Director, Experimental Sciences

advisory, thought-leadership, field-building and policy • They have inspired and mentored more than 160 other dialogue role in the collaborative efforts to tackle NTDs. AbbVie scientists to get involved. Although executives Dr. Kempf, for example, serves as a member of the at the company have given their clear support to the Scientific Advisory Boards of Drugs for Neglected Diseases Neglected Diseases effort, they do not require any of the initiative (DNDi) and the Global Alliance for TB Research. company’s scientists to participate. The scientists who Dr. Marsh serves on several MMV development teams and are donating their time and expertise at different levels informally advises each NTD partner. of the R&D organization and in different teams and ways, are doing so on a pro bono basis driven by their personal • They have led most of the project management and decisions. Many of them got engaged, especially in the relationship building aspects of AbbVie’s engagement early stages, through the encouragement and role models with its nonprofit product development partners. of Dr. Kempf and Dr. Marsh. As Dr. Marsh explains it, Although these nonprofit organizations benefit from the “There is always some ‘white space’ in everyone’s working scientific and technical platforms that AbbVie and other life. Because it is inspiring and different, and we take the pharmaceutical and biotechnology companies can offer effort to explain the value of the contribution, many of our them, these are non-traditional relationships, in most cases scientists want to help. We tap into each other’s networks without tried and tested approaches. In some cases there to make it all possible.”9 In addition to current employees, has also been a legacy of mistrust between the public Dr. Kempf and Dr. Marsh have also enabled several of the health community and commercial companies. Even if not company’s retired scientists to get actively engaged in the directly with these specific organizations, this is a broader initiative on a volunteering basis. One such example is challenge that needs to be addressed. As such, in order for Dr. von Geldern, who is profiled briefly in Box 1. the partnerships to be successful, there is an ongoing need for trust building, clarity of roles and responsibilities, good • Dr. Kempf and Dr. Marsh have also played a crucial communications, team building and mutual respect—all internal leadership and coordinating role as members of of which take time and require effective relationship the company’s Executive Council on Neglected Diseases, management skills above and beyond any scientific and and by continuing to make a compelling case to senior technical assistance. executives about the value of this pro bono initiative to the company, to its partners, and to furthering the agenda of global public health more broadly. As Dr. Kempf has commented, “…both of us are at a place in our careers that enables us to accomplish a lot in doing this type of work— people listen. Although this is a grassroots program with no formal budget or staff allocation, we have been able to engage our colleagues to work alongside us and senior management to give us support.”10

14 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

Box 1 Profiles in scientific leadership

These brief profiles illustrate the level of scientific expertise and leadership that three of the leaders in AbbVie’s Neglected Diseases initiative are able to share with their internal colleagues and external partners:

Dr. Dale Kempf is the Distinguished Dr. Kennan Marsh is Director of Dr. Tom von Geldern spent over 20 Research Fellow and Director, Experimental Sciences and Senior years in the , Neglected Diseases Research at Research Fellow at AbbVie. She has serving among other roles as a AbbVie. He has more than 30 years of more than 30 years of experience in Research Fellow and Senior Group experience in pharmaceutical R&D, pharmaceutical R&D, with a major focus Leader at Abbott Laboratories. In this mostly in antiviral research. He is the in preclinical compound optimization. capacity he led medicinal chemistry co-inventor of AbbVie’s HIV protease As the head of the nonclinical efforts resulting in the identification inhibitors Norvir® and Kaletra®. pharmacokinetics group for >20 years, of clinical candidates in the areas of Subsequently, Kempf co-directed her team contributed to small molecule oncology, , cardiovascular AbbVie’s hepatitis C (HCV) projects spanning antivirals, oncology, and metabolic diseases. Since his discovery program, leading to the neuroscience, metabolic diseases retirement from Abbott in 2007, he has development of Viekira Pak®, AbbVie’s and immunology. With expertise in been an independent consultant to the combination treatment for HCV. pharmacokinetics, drug metabolism pharmaceutical and biotech industries, He currently serves on the company’s formulation, bioanalysis and toxicology, specializing in medicinal chemistry and Scientific Governing Board and she has worked with project teams discovery strategy and tactics, and with Medicinal Chemistry Leadership Team, to integrate available information for a particular focus on the development and directs its cross-divisional initiative compound selection and progression. of treatments for neglected tropical to bring AbbVie resources to partners Currently, Dr. Marsh directs her efforts diseases. He has served as a volunteer working on underserved disease areas. to the NTD partners, providing similar board member or advisor to a Dr. Kempf has received a number expertise for compounds under number of health-related nonprofit of scientific and industry awards, evaluation by DNDi, TB Alliance and organizations, and he and his wife published widely in areas of medicinal MMV. Recently Dr. Marsh received an are actively engaged in community- chemistry, pharmacology and drug award from the Scientific Governing level volunteering, especially on resistance, with more than 120 scientific Board for her broad impact across environmental issues. He is an author of publications and 50-issued United AbbVie R&D. She has published widely 84 peer-reviewed articles, an inventor States patents to his credit. in areas of pharmacokinetics, with on 52 US patent applications, and has more than 240 authored or coauthored lectured by invitation on more than 65 publications and more than a dozen occasions. issued US patents.

“As drug discovery scientists, we tend to have an idealistic view of our job; we’re advancing scientific understanding, and at the same time working to improve human health. To pursue these goals, for the benefit of patients whose health needs have historically been neglected…it just doesn’t get any better than that! AbbVie has generously provided infrastructural support that allows me, and some of our other retired scientists, to participate in their effort.” Dr. Tom von Geldern, AbbVie Retiree and volunteer

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 15 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

Engaging in product development • Sharing compounds for screening – Prior to the creation 3partnerships of these and other cross-sector PDPs, the vast majority of chemical compounds in pharmaceutical company libraries A core strategy of AbbVie’s Neglected Diseases initiative had never been tested against the causing NTDs. has been engaging in product development partnerships The ability to access well-annotated compound libraries (PDPs) with a small number of nonprofit, science-based and then screen thousands of these compounds is a crucial organizations that are committed to tackling NTDs, and are early stage in the R&D process of identifying potential open to working with companies, alongside governments drug candidates. As DNDi noted in a ten-year review of and other research partners to achieve their goals. Diagram 5 its experiences and lessons, “Gaining access to classes of illustrates the general division of labor between the key types compounds with drug-like characteristics from companies of organization engaged in such partnerships, and illustrates is vital as it offers access to knowledge and know-how AbbVie’s approach to engagement. associated with compound series to ensure more efficient drug development.”11 Since 2009, AbbVie has provided its This case focuses on AbbVie’s engagement with the Drugs nonprofit partners with more than 120,000 compounds for Neglected Diseases initiative (DNDi), Medicines for Malaria for screening. The engagement has ranged from targeted Venture (MMV), TB Alliance and TB Drug Accelerator (TBDA), screening of compounds with anti-infective activity to Anti-Wolbachia Consortium (A-WOL), and Macrofilaricidal high-throughput screening (HTS) of random collections. Drug Accelerator (MacDA). These PDPs are profiled on pages The largest screening campaign has been with the 18-25. The company’s partnerships with these organizations Infectious Diseases Research Institute (IDRI) in the context are focused around three main areas of activity: of the TB Drug Accelerator, followed by the company’s partnership with DNDi. The company initially provides samples for testing, and then certain active ones that are scientifically interesting are donated.

Diagram 5 The Product Development Partnership Model

Funding Agencies Regulators BMGF, Wellcome Trust etc WHO, FDA, EMA

AbbVie & other companies Compounds, Expertise, PDP Endemic Countries Preclinical Studies Strategy, Coordination Clinical

Contract Research Organizations University Researchers Discovery, Preclinical , Chemistry

Source: AbbVie

16 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

• Supporting program enhancement – AbbVie scientists • Providing technical expertise and advice – Although are also adding value to selected PDP programs by the PDPs have been able to attract remarkable scientists providing a pro bono service in areas where the company to work for them, they also need to be able to draw has particular expertise or technology that can move on a much greater breadth and depth of scientific partner programs more rapidly towards ‘go’ or ‘no go’ expertise and experience than is possible in a relatively milestones. Dr. Kempf explains, “We work with our partners small organization. A number of AbbVie’s scientists to identify opportunities that are likely to have the biggest serve as advisors and consultants on a pro bono basis impact—matching the company’s capabilities with our to these initiatives. Dr. Kempf, for example, serves on partners’ needs. Regardless of where the relevant program DNDi’s Scientific Advisory Committee, which advises the or compounds come from, if they look promising based organization on matters related to R&D and the choice on initial screening we can provide partner organizations of projects as well as quality of the scientific work and with valuable, low-cost and good quality information in on a similar body for the TB Alliance. Dr. Marsh provides key areas such as safety and toxicology through running expertise to all of AbbVie’s NTD partners, and particularly both routine and specialized assays and tests. In this way with MMV on preclinical development aspects for several we are able to harness the scale of our technology platform of their compounds. as well as our scientific and process expertise to provide substantial in-kind support worth thousands of hours In addition to formal advisory roles, many of the in terms of scientists’ time and costs.”12 To date, AbbVie participating AbbVie scientists are also available to provide scientists have undertaken hundreds of scientific tests on technical expertise and advice on a more ad hoc basis as behalf of their product development partners. needed and requested.

Diagram 6 NTD Partnership Projects: Contributions by Year

Since 2011, AbbVie’s scientists have increased the number of volunteer hours contributed to the product development partnerships they are engaged with from about 5,000 a year to more than 17,000 hours a year. The allocation of these hours among activities in discovery, development sciences, drug product development and process chemistry is summarized below.

2011

2012 Discovery 2013 Development Sciences Drug Product Development Process Chemistry 2014

2015

0 Hours 3000 6000 9000 12000 15000 18000 Source: AbbVie

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 17 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

3.1 DRUGS FOR NEGLECTED DISEASES initiative (DNDi)

DNDi was one of the first product in Tropical Diseases (TDR), acting as a formulations of existing drugs, and development partnerships to bring permanent observer to the initiative. strengthen capacity in disease-affected together public and private research Today, DNDi’s funders number over countries and communities to enhance institutions with the goal of developing 60 public institutional donors, private local research and clinical trials and safe, affordable and effective treatments foundations and private individual improve treatment delivery. for patients suffering from the most donors. neglected tropical diseases in countries In the short-term, the network of with some of the most limited To achieve its goals, DNDi has pioneered partners aims to improve existing healthcare systems. It was created in innovative agreements to partner on treatments, making them more 2003, following recommendations of drug discovery, development and affordable, safer, easier-to-use and a working group established by the treatment activities with over 150 effective. Over the long-term it aims humanitarian organization, Médecins pharmaceutical and biotechnology to develop new drugs. As of 2015, six Sans Frontières (MSF). In addition to companies, universities, public and new treatments had been delivered MSF, its founding supporters were private research institutes, contract to millions of patients, and a pipeline five public sector institutions—the research organizations, Ministries of established of 13 new drug candidates. Foundation from Brazil, Health, hospitals, NGOs, and other DNDi and its partners are also active in the Indian Council for Medical Research, product development partnerships, advocacy to promote public awareness, the Medical Research Institute, It operates as—and coordinates—a and increase public policy and financial the Ministry of Health of Malaysia and ‘virtual research ecosystem’ whereby support for NTDs. France’s , with the these diverse partners collaborate UNDP / World Bank / WHO’s Special on targeted projects to discover and Programme for Research and Training develop new drugs, produce new

Box 2: NTDs focused on by DNDi

DNDi currently focuses on five of the most 350 million people at risk in 98 countries, Paediatric HIV/AIDS, which affects 3.3 serious NTDs in terms of the numbers of and children the most affected. million children, mostly in Sub-Saharan people at risk or infected, and the spread Africa. Without treatment, over half of and severity of the disease. They are:13 Chagas disease or American these children will die before they are Trypanosomiasis, which is the leading two and 80% by the age of five, resulting Sleeping Sickness or Human African cause of infectious heart disease in Latin in 600 children currently dying every day. Trypanosomiasis (HAT), which causes America, with over 100 million people at severe mental debilitation and and risk, 8 million infected and some 12,000 DNDi previously supported research on can kill if left untreated, with 36 million every year. malaria, but has transferred this portfolio people at risk, especially in 8 African of work to Medicines for Malaria Venture countries. Filarial Diseases, which cause (MMV). Since 2015, it has also started blindness, swollen limbs and genitals, working on mycetoma and Hepatitis C. Leishmaniasis or Kala-azar, different intense itching and chronic pain, with types of which cause either , weight about 1.5 billion people at risk, and 25 loss, / swelling, anaemia and million infected with potential fatality or disfiguring (river blindness) and 120 million with lesions and social stigma, with more than (elephantiasis).

18 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

3.1 DRUGS FOR NEGLECTED DISEASES initiative (DNDi)

DNDi’s agreements with its partners are • Provision of more than 35,000 Targets for the partnership between structured to facilitate transparency in compounds for screening against AbbVie and DNDi in 2016 include its R&D activities as well as accessibility , Chagas disease, demonstrating progress on one new and affordability of any drugs and onchocerciasis, and lymphatic compound for Chagas or Leishmaniasis treatments that result from them, filariasis. Promising lead compounds into hit-to-lead and renewing and while also clarifying and protecting from these screenings are fed into expanding the DNDi collaboration intellectual property (IP) ownership, an ongoing discovery collaboration. agreement to include additional active which is usually retained by the partner In 2014-2015, three new progressible series. and in some cases co-owned, and hit series for filarial disease and one facilitating licensing. In this way, DNDi progressible hit series for leishmania A note on drug discovery maintains clear financial and scientific were entered into the AbbVie- terminology: High throughput independence, while being able to DNDi collaboration agreement, screening (HTS) techniques are used catalyze and leverage world-class allowing for further study of these to screen thousands of compounds research by drawing on the scientific, compound series. Additionally, a and to select a few promising active technical, material and financial characterization of T cruzi inhibitor compounds. Hit-to-lead is the stage at resources of its public and private hits was completed, and one series which these hit molecules from HTS partners to advance its mission. of inhibitors was progressed into hit- are evaluated and undergo limited to-lead. This joint venture provides optimization to identify promising lead AbbVie has been one of DNDi’s DNDi with access to selected classes compounds. In the subsequent lead corporate partners since 2009, of AbbVie’s proprietary molecules, optimization stage, many new analogs expanding the partnership in recent and AbbVie scientists participate in are synthesized and evaluated in an years. In 2011, they signed a four-year the collaborative Discovery team to iterative process to identify optimized joint research & non-exclusive licensing identify new preclinical candidates. preclinical drug candidates, which then agreement to undertake research on pass from the discovery phase into new treatments for Chagas disease, • AbbVie also participates in the preclinical drug development. helminth , leishmaniasis DNDi Lead Optimization Latin and sleeping sickness, which is America (LOLA) team. Through this currently being renewed. IP related collaboration, AbbVie provides advice to this agreement, existing relevant and helps to characterize DNDi’s lead AbbVie IP and new IP generated by compounds, providing high-quality this collaboration will be subject to a scientific results at no cost to DNDi. principle of non-exclusive licensing to address NTDs in endemic countries. • In addition to the project-based Any products developed as a result technical expertise and advice that of this partnership will be provided is provided by AbbVie scientists to endemic countries at the lowest through the above activities, Dr. Kempf sustainable price to ensure the greatest also provides broader strategic advice patient access. Joint projects underway on R&D issues as a member of DNDi’s currently include: Scientific Advisory Committee.

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 19 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

3.2 MEDICINES FOR MALARIA VENTURE (MMV)

Approximately 3.2 billion people live commercial viability and investment in Cipla, that develop and manufacture at risk of malaria, and some 438,000 R&D. As of 2015, MMV had successfully antimalarial drugs and on a die from the disease every year, most grown to more than $850 million in commercial basis. At the same time, of them children. Many infected adults received or pledged funding from a number of companies that do not face not only poor health, but also a some twenty government agencies, have commercial interests related to loss in their work productivity, wages private foundations, international malaria are engaging with MMV on a and household income, exacerbating organizations, corporations, corporate pro bono basis, of which AbbVie is a the cycle of poverty. The disease costs foundations, and private individuals. good example. Africa an estimated $12-30 billion in lost GDP annually, and accounts for some A crucial factor in MMV’s success MMV describes how its engagement 40% of all public health spending on has been its partnership-based with companies, “leverages the the continent.14 research network including over 400 facilities, knowledge and expertise of pharmaceutical and biotechnology the pharmaceutical and biotechnology Medicines for Malaria Venture (MMV) companies, universities, international industries, drawing on their valuable is a product development partnership research institutes and country-level experience and resources at every stage aimed at “discovering, developing and public, private and nonprofit partners in of the drug development process and facilitating delivery of new, effective 50 countries. Its research approach and applying it to our own. …where MMV and affordable anti-malarial drugs” to portfolio are outline in Box 3. is funding a research program, we reduce the burden of malaria in the expect the partner, at a minimum, to most severely affected countries.15 Pharmaceutical and biotechnology match the value of the contract through It was established in 1999 with companies have been increasingly in-kind contributions (for example staff initial financing of $4 million from important participants in MMV’s costs, laboratory space, equipment, government donors and private research network. This has been overheads), thus maximizing MMV’s foundations, with the recognition that especially the case for those companies, financial resources.”16 there were insufficient anti-malarial such as GlaxoSmithKline, Sanofi, Pfizer, treatments being developed due to low , Guilin Pharmaceutical and

Box 3: MMV’s research approach and portfolio

MMV’s research network focuses on, vivax (including radical ), efficacy 5 million compounds, advanced new “delivering efficacious medicines that are against severe malaria, and - drugs along the development pipeline, affordable, accessible and appropriate for blocking treatment.”17 demonstrated the potential of new use in malaria endemic areas. Specifically, technologies and delivery channels, and the goal is to develop products that will Today, MMV is regarded as managing one dispatched 300 million treatments of provide: efficacy against drug-resistant of the world’s most significant portfolios Coartem® Dispersible, and delivered 36 strains of falciparum, of anti-malarial R&D with over 65 projects million vials of injections, potential for intermittent treatments underway covering the spectrum of both of which are life-saving medicines. ( and ), safety in small research, translational and development children (less than 6 months old), safety in activities. To-date, together with its pregnancy, efficacy against Plasmodium partners, MMV has screened over

20 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

3.2 MEDICINES FOR MALARIA VENTURE (MMV)

AbbVie started to collaborate with to the development of formulations information on the ”pharmaceutical MMV in 2010. Their partnership has optimized for treatment of malaria in properties” of the compounds, focused primarily on AbbVie scientists tropical climates. In 2015, IND overview AbbVie has contributed to the in vitro supporting preclinical program documents were completed by AbbVie characterization of the compounds in enhancement for one of MMV’s major scientists to support the IND filing for the Box, with in vitro profiles drug candidates—DSM265—and DSM265. of metabolic stability, binding, DSM421, a potential follow-on solubility, permeability, the potential compound for DSM265. The collaboration At present, AbbVie scientists are for drug-drug interactions and cellular also extends to earlier nonclinical contributing expertise towards the . optimization of alternate chemical conduct of long term toxicology series. studies and specialized toxicology In 2016, AbbVie will assist MMV with studies which evaluate the safety for the toxicology studies required prior • DSM265: The collaboration focused future dosing of DSM265 in children to dosing in children and pregnant originally on DSM265, which if and pregnant women. women as well as those studies successful could result in a potential required for repeated dosing in humans. single dose cure for malaria. DSM265 • DSM421: AbbVie is also contributing AbbVie will also conduct a clinical inhibits the plasmodial pyrimidine to the nonclinical development plans study with DSM265 to characterize the biosynthetic enzyme dihyroorotate for DSM421 (considered a ”next pharmacokinetics of a new, more cost dehydrogenase (DHODH), an enzyme generation compound”), a more effective formulation developed for essential to soluble version of DSM265. As with tropical regions. (P.f.) and (P.v.) DSM265, the AbbVie contributions to parasites. It has now completed DSM421 have centered around gaining Phase I study which characterized the an understanding of metabolism pharmacokinetics and safety following (through metabolite ID studies) single oral doses in healthy volunteers. and the pharmacokinetic profile in Phase IIa clinical trials on DSM265 selected nonclinical species (monkey, continue in and an Investigational dog, pig). Toxicology study design New Drug application (IND) was and interpretation are part of the opened with the Federal Drug company's ongoing contributions Administration (FDA) in December, to the preclinical characterization of 2015. DSM421.

Prior to clinical development, • Next Generation Compounds: AbbVie conducted studies to To stimulate the discovery of drugs for profile the pharmacokinetics in neglected diseases, MMV has gathered mice, dogs, pigs and monkeys and 400 diverse drug-like molecules which assisted in metabolite identification are made available for free to research (understanding of how the body teams (Pathogen Box). The compounds breaks down the compound). AbbVie have confirmed activity against at least contributed to the development of one of the key pathogens that cause the formulation used in the Phase 1 some of the most neglected diseases study and continues to contribute on the planet. To provide additional

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 21 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

3.3 THE TB ALLIANCE and TB DRUG ACCELERATOR (TBDA)

Tuberculosis (TB) is now the world’s treatments, which can lead to increased are available to those who need them.”19 leading infectious killer. In 2014, it transmission, higher mortality rates, Similar to its fellow PDPs, it aims to, “… resulted in 1.5 million deaths, about and the growing challenge of drug combine the research and development 9.6 million infections, and some 480,000 resistance. expertise of its own staff with the skills multidrug-resistant (MDR-TB) cases.18 and resources of its partners (which There is also the ongoing challenge The TB Alliance was established as include pharmaceutical and biotech of people suffering from co- a nonprofit product development companies, research institutes and with TB and HIV. The vast majority partnership in 2000, in recognition NGOs, academia, donors, governments of people affected are among low- of the fact that at time there were no and patients groups) to harness the income populations in developing TB drugs in clinical development, due most promising science wherever it countries. The human and economic mainly to the lack of market incentives may exist around the world. The model costs of TB are exacerbated by the fact to develop them, despite the need minimizes costs, including overhead that existing drugs and therapies are for new drugs and the potential for and investments in infrastructure, while not only outdated, but also require scientific innovation. The TB Alliance optimizing scientific capacity to speed a minimum of six months to cure is dedicated to, “the discovery and new TB drug development.”20 Today, patients. This long treatment regimen in development of better, faster-acting the TB Alliance manages the largest turn contributes to high default rates on and affordable tuberculosis drugs that pipeline of new TB drugs in history.

Box 4: Accelerating progress on TB research through increased collaboration

In August, 2012, the Bill & Melinda Gates Their goal is to dramatically accelerate TBDA’s model is one of unprecedented Foundation (BMGF), with urging from the discovery and development of collaboration. It breaks from traditional the CEO Roundtable, took ongoing an affordable TB treatment that will R&D practices, which result in silo’ed collaborative efforts in TB research cure patients in one month instead of work streams, no sharing of compounds, a step further by establishing the TB the current six months, and thereby and often redundant research efforts, Drug Accelerator (TBDA). Currently keep more people on treatment, to an approach that is based on under the TBDA, eight companies reduce mortality and reduce resistance collaboration at the early stage of drug (AbbVie, AstraZeneca, Bayer, Eli Lilly, development. They are working together discovery, sharing of compound libraries Eisai, GSK, Merck & Co. and Sanofi), work to generate multiple mechanistically and data, better coordination, and joint alongside eight research institutions distinct TB drug candidates sufficient to efforts to develop the best prospects, and universities (the Infectious Diseases advance a drug regimen to a one-month regardless of where the drug originates. Research Institute, the National Institute clinical proof-of-concept by 2024. of Allergy and Infectious Diseases (NIAID), the Drug Discovery Unit at Dundee University, the California Early Data Companies work collaboration sharing on each other’s Institute for Biomedical Research (Calibr), compounds Texas A&M University, Weill Medical College at Cornell University, Rutgers Avoid Maximize Overcome Biomedical and Health Science, Colorado redundancy efficiency competitive State University and the University of barriers Cape Town), and the TB Alliance, with participation from BMGF. ONLY THE BEST CANDIDATES ADVANCE Source: TBDA Source:

22 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

3.3 THE TB ALLIANCE and TB DRUG ACCELERATOR (TBDA)

Diagram 7 Bringing compounds from library to development: How the TBDA works

Hit Generation 2019 new preclinical Company Collaborative Hit & Lead candidates compound discovery Optimization libraries research 2024 1 month, 3-drug regimen Target Identi cation proof of concept Source: TBDA Companies work on each other’s

Since 2012, AbbVie scientists have • Within the TBDA, AbbVie also In addition, millions of compounds provided technical expertise for provides substantial in-kind support are being ‘virtually screened’ several TB Alliance programs. for other sub-teams’ programs, against other TB protein targets Dr. Kempf serves on the TB Alliance conducting discovery and preclinical through computational techniques, Scientific Advisory Committee and studies on compounds from the after which the predicted active AbbVie provides preclinical support for University of Dundee, the University compounds are sent for actual testing. selected TB Alliance programs, recently of Cape Town, Texas A&M University, completing three screening toxicology and the TB Alliance. These studies In 2016, the scientists are focused on studies on their behalf. The company’s provide early information on the progressing additional series into hit- bilateral discovery partnership with the safety of compounds being explored to-lead and completing the screening TB Alliance has been superseded by a in the partners’ programs. of a large AbbVie compound collection research collaboration within the TBDA. against a second TB protein target. This currently includes the following • Collaborative screening efforts are activities: also currently underway with NIAID, Cornell University, and Texas A&M • AbbVie has provided over 100,000 University. These studies provide proprietary compounds for information about the activity of screening against the TB bacteria. compounds against TB under other Any promising screening hits are conditions found in the human disclosed to TBDA members and or look for new active compounds advanced within a collaborative through alternate screening drug discovery TBDA sub-team techiques. These techniques can consisting of AbbVie, Eli Lilly, and the allow for even higher numbers Infectious Disease Research Institute of compounds to be assessed; (IDRI). In 2014-2015, seventeen new for example, a collection of over progressible hit series from screening 250,000 AbbVie compounds was of the AbbVie compound collection screened at AbbVie against a TB were disclosed to the TBDA. protein target provided by NIAID.

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 23 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

3.4 THE ANTI-WOLBACHIA CONSORTIUM (A-WOL) and MACROFILARICIDE DRUG ACCELERATOR (MacDA)

Filarial worm or infections a drug with permanent sterilization and the LSTM, through which AbbVie cause a number of the most debilitating capabilities and the development of provided a small subset of its neglected tropical diseases including by the worms.22 collection for screening. This effort, onchocerciasis (“river blindness”) and and subsequent evaluation at LSTM, lymphatic filariasis (“elephantiasis”). The A-WOL consortium was founded the University of Bonn and TRS Labs, in 2007 to address these challenges led to the identification of Tylosin A as Onchocerciasis affects up to 37 million with grants of over $40m from the Bill an important lead compound. AbbVie people, especially in Africa, and results & Melinda Gates Foundation (BMGF). then launched a medicinal chemistry in skin disease and blindness, with Its aim is to discover and develop new optimization effort in conjunction some 500,000 people becoming blind anti-Wolbachia drugs with shorter and with the Franciscan Institute for World as a result of the disease. It is caused more effective activity and to improve Health, leading to the identification by a large worm () regimens of existing treatments for use of analogs that were highly active in which is transmitted to humans by as alternative strategies where needed, animal models of filarial disease. black that breed in tropical rivers as well as raising awareness of the As this so-called TylAMAc (“Tylosin and streams. Lymphatic filariasis is the urgent need to tackle these diseases Analog Macrofilaricide”) program 2nd leading cause of global disability. and the barriers to their elimination advanced, the collaboration expanded It is caused by nematode worms that goals and targets. Its approach is to in 2014 to include DNDi, which received live in the lymphatic vessels of humans target Wolbachia—which is a type of a grant from the BMGF to work on and affects an estimated 120 million symbiotic bacteria that lives inside the pre-clinical and clinical development in people in more than 80 countries, with cells of the parasitic worms. The worms filarial diseases. more than 1.5 billion people at risk are dependent on these bacteria for of infection. People affected with the their development, fertility and survival, In 2014-2015, two lead compounds disease can develop severely swollen and so eliminating the bacteria with were identified as possible preclinical limbs and thickened skin resulting in antibiotic drugs will kill the worms candidates for onchocerciasis and loss of mobility, poor quality of life, and and deliver a new, practical and cost- lymphatic filariasis: A-1535469 and often social stigma and exclusion.21 effective solution for eliminating A-1574083. They were approved by these diseases.23 the Scientific Advisory Committee of Control of filariasis currently relies the A-WOL Consortium and DNDi’s on (MDA) The A-WOL Consortium is coordinated Preclinical Candidate process to be programs that are dependent on the by a management team based at the advanced through additional efficacy, longstanding and generous drug Liverpool School of safety, and toxicology studies. These donation programs for Mectizan® (LSTM), and consists of internationally two preclinical candidates were scaled ( from Merck & Co. Inc) recognized scientists working in up to >3kg to support initial two-week and albendazole from GSK. Eisai academic and corporate laboratories. toxicology studies in both rats and also donates DEC. These drugs are AbbVie initially engaged with the dogs. The A-1574083 compound was administered singly or in combination A-WOL Consortium in 2010, and the candidate selected by DNDi in 2016 through community-based treatment, relationship has evolved into the and is progressing through further and need to be taken for extended following two initiatives: toxicology studies, ultimately leading to periods to cover the reproductive the initiation of studies in humans. lifespan of the long-lived adult worms. The TylAMac Program Current treatment and eradication This program began as a screening Scientists from AbbVie and LSTM challenges include the absence of partnership in 2010 between AbbVie presented the first results from this

24 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

3.4 THE ANTI-WOLBACHIA CONSORTIUM (A-WOL) and MACROFILARICIDE DRUG ACCELERATOR (MACDA) program at the BMGF Grand Challenges AbbVie has served as a founding meeting in Beijing and the American member of the consortium with the Society of Tropical Medicine and goal of consolidating and synergizing Hygiene conference in Philadelphia overlapping streams of research. in October 2015. Within the MacDA, AbbVie participates The Macrofilaricide Drug Accelerator in a dedicated drug discovery sub-team (MacDA) along with DNDi, the University of Building on the success of the TB Drug Bonn, and the Northwick Park Institute Accelerator model for collaborative for Medical Research. A library of more tuberculosis drug discovery, in 2014 the than 700 selected high-quality AbbVie BMGF proposed a similar approach to compounds was initially screened, the development of new agents to kill resulting in the identification of four adult filarial worms (“macrofilariae”). novel series of leads that directly attack The MacDA (Macrofilaricidal Drug the filarial worm, as opposed to the Accelerator) was established in TylAMac compounds that attack the March 2015 as a collaborative symbiotic bacteria. These are now being venture between 11 companies, advanced through hit-to-lead, with research institutions, and nonprofit AbbVie scientists guiding the medicinal organizations to discover and advance chemistry aspects of the program. It is new macrofilaricides for the treatment hoped that in 2016 one of these series and elimination of onchocerciasis and can be optimized toward a potential lymphatic filariasis. preclinical candidate.

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 25 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

"AbbVie’s multigenerational NTD drug discovery team is made up of chemists, biologists, biochemists, pharmacologists, computer scientists, managers, technicians, administrative assistants, and lawyers. It is the personal involvement that these individuals have with the interns each summer that has the greatest impact. Through these relationships the students begin to appreciate what is not learned through a textbook, classroom, or laboratory course. It is not only personal passion and drive that is passed on through shared experiences, but also the oral tradition and institutional memory of a well-established pharmaceutical company. These relationships also provide renewed energy and job satisfaction for the seasoned and retired scientists, as well as an opportunity to give back with their professional talents and expertise both in the education of the next generation of scientists and in the immediate impact that these projects can have on people afflicted with NTDs today." Dr. Jeffrey Rohde, Professor of Chemistry, Franciscan University

Supporting the education of future Immersed in a state-of-the art scientific environment, 4scientists and health leaders students learn to: • Conduct drug discovery research; In addition to mobilizing more than 160 of AbbVie’s own • Follow and evaluate experiments using the latest scientists, since 2011, another element of the Neglected techniques and technologies; Diseases initiative has been co-sponsoring a summer • Record progress and results in electronic-notebooks; internship program with the Franciscan Institute for • Register compounds into AbbVie’s compound repository; World Health (FIWH) based at the Franciscan University of and Steubenville, Ohio. • Regularly give updates on their progress in team meetings.

The aim is to provide educational, humanitarian, and The summer concludes for each intern with a poster scientific career training to undergraduate science students presentation to the larger company, a summary lecture to working on NTD projects. AbbVie scientists provide hands-on the full project team, and a comprehensive professional supervision and coordinate student projects with AbbVie’s performance evaluation of their summer work by the team NTD partners. The internship is a ten week, 40 hour/week, and project leaders. intense experience of full-time collaborative research on NTD targets side-by-side with AbbVie drug discovery scientists Over thirty interns, representing more than a dozen colleges and Dr. Jeffrey Rohde. Dr. Rohde is a previous in-house and universities and including international students from medicinal chemist of nearly 13 years at Abbott, current , Singapore, and Trinidad-Tobago, have participated in Professor of Chemistry at Franciscan University, founder the program over the first five-years. Most of those interns, of the FIWH NTD Initiative, and co-director of the summer upon completion of their undergraduate degrees, have internship program together with Dr. Kempf. embarked on the next step in their educational progressions in doctoral programs and medical schools. A few, based upon The specific drug targets and collaborative projects for the and with the benefit of this industrial experience, summer are determined in real-time by AbbVie’s strategic have gone directly into the health sciences workforce at partnerships with organizations like the DNDi. Interns entry level positions. assume responsibility for a critical step in this global effort: preparing new compounds and developing new assays The internship program has also led to an increase in student- for potential novel drug therapies. In 2014 and 2015, for led NTD research projects at the university, a campus-wide example, the students conducted projects focused on TB, summer research program, and a number of similar programs Chagas disease, onchocerciasis and leishmaniasis, producing being established at other universities, as well as two new a number of compound series for testing through their programs that will be piloted this summer with Abbott and screening efforts. Eli Lilly.

26 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

Funding community projects and leads to extensive destruction of skin and soft tissue with 5dialogues the formation of large ulcers usually on limbs. Only about 30 percent of cases are healed without disabilities. More than In addition to leveraging the expertise of its people, 2,500 cases have been reported in the country, accounting philanthropic support is provided through the AbbVie for over half the cases reported worldwide. Foundation to partners that are tackling NTDs. The foundation’s mission to build “strong communities, sustainable healthcare AbbVie’s support is focused on 97 health facilities in three systems and effective educational programs” that help to meet of the country’s most endemic health districts. The program the needs of some of the world’s most underserved people.24 focuses on improving early detection, strengthening disease surveillance, monitoring and evaluation systems as well as A core element of the foundation’s strategy is to partner early detection and patient care for BU patients in these with experienced humanitarian and public health nonprofit districts, with the goal of minimizing BU-related morbidity organizations that have on-the-ground delivery capability and preventing long-term disability. and a solid evidence-based approach to selecting projects and measuring progress. The foundation works with global During 2014-2015, the program standardized collection tools and local partners in both the nonprofit and public sector and data processing methods, and consolidated district-wide across a number of countries and on a number of global data into an electronic database. These improvements in health challenges of which NTDs is just one. data collection, reporting and management in turn made it easier for staff to monitor the distribution of positive BU cases In the area of NTDs, the foundation is working with MAP in the project districts. The program also emphasized the International and the Sabin Vaccine Institute to support select importance of patient adherence, which has remained high community-based interventions and evaluations aimed with at least 95% of patients on completing their at advancing NTD programs and reaching underserved full course of treatment. populations in parts of Africa and Latin America. Additionally, previously the foundation funded efforts to prevent and Another focus has been building the capacities of health control lymphatic filariasis in . workers and local communities. In 2015, the program provided education sessions on BU case management and 5.1 MAP International in Côte D’Ivoire and Bolivia disease surveillance, which trained 120 community health The foundation works with MAP International in Cote D’Ivoire workers, reached over 14,000 students in primary schools and Bolivia. MAP International combines medical assistance and educated more than 13,000 community members about with programs to train, equip and empower individuals BU case detection awareness. Nearly 90% of suspected BU and families living in poor communities, so that they are cases underwent confirmatory diagnostic testing, exceeding better able to prevent and fight diseases and improve the the goal of 60%. These and other activities also helped to conditions they live in more broadly. Its three core focus enhance overall health system capacity and community areas are: the provision of essential medicines and medical response mechanisms to BU prevention and control. supplies, disaster and emergency relief and treatment and prevention of neglected tropical diseases. To achieve these results, MAP has worked with and supported the priorities of the National Buruli Ulcer Control Programme, Tackling buruli ulcer in Côte D’Ivoire the Directorate of Forecasting, Planning, Evaluation and In 2010, the AbbVie Foundation (at the time still the Abbott Health information, and the Pasteur Institute of Côte D’Ivoire. Fund) launched a buruli ulcer (BU) program in several health This offers a good example of how a private sector foundation districts in Côte D’Ivoire, in support of an ongoing initiative can support the work of an NGO implementing partner in led by MAP International. Côte D’Ivoire is the world’s most a way that aligns with government public health priorities endemic country for buruli ulcer. It is caused by a germ, and enhances a more systemic approach to problem-solving, Mycobacterium ulcerans which results in infection that often drawing on the resources and capacities of all sectors.

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 27 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

Addressing chagas disease in Bolivia and with support from the Colombian Ministry of Health In 2014, the AbbVie Foundation partnered with MAP and provincial and local health staff to reach 18 indigenous International in Bolivia, where 80 percent of the country is communities in the country’s Vaupes province located endemic for chagas disease, with 1.8 million people at risk in the remote Amazonas region. The program focused of infection.25 Left untreated, the disease can lead to serious on improving the coverage for prevention, control and heart, digestive, neurological and systemic conditions. elimination of five prioritized neglected tropical diseases of soil-transmitted helminths (STH). STH is a public health The focus of the foundation’s support in this country is on problem in the province, which has the highest frequency of community-driven activities aimed at training community infection in the country. health workers in prevention, raising community awareness, disease surveillance, screening, early diagnosis and In addition to providing treatment, the program also improving the treatment referral process. In addition, efforts undertook hygiene and complemented by are underway to implement environmental control strategies home visits and a community health surveillance system to targeted at preventing and controlling chagas disease, with ensure more healthy housing practices to reduce the risk of the ultimate goal of elimination. these diseases. The program successfully strengthened local capacity of health institutions in indigenous communities by With AbbVie Foundation support in 2014, MAP operated in training for local disease surveillance. 33 communities training community healthcare workers and healthcare professionals, conducting home visits to identify Assessing progress of STH and malaria programs in Mexico vulnerable families and repairing selected homes reaching In 2014, the AbbVie Foundation provided the Sabin Institute nearly 3,000 community members. The program was a research grant to assess the impact of the national expanded in 2015 to reach over 7,000 community members albendazole program by determining the prevalence and in 40 different communities with continued expansion intensity of infection of soil transmitted helminth (STH) expected in 2016. infections and asymptomatic malaria infections among school-aged children in ten of the poorest states in Mexico. 5.2 The Sabin Vaccine Institute in Latin America The Sabin Vaccine Institute is a nonprofit organization that The study is being conducted in collaboration with the Pan was founded in 1993 by a group of scientists, researchers American Health Organization (PAHO), the National Center and advocates. It is named in honor of the oral vaccine for and Adolescent Health (CeNSIA), the Institute developer Dr. Albert B. Sabin. One of its main programs is the of Epidemiological Diagnosis and Reference (InDRE), and Global Network for Neglected Tropical Diseases, which aims the National Center of Disease Prevention and Control to raise the awareness, political will, and funding necessary to (CENAPRECE). Again, this offers a useful model of public- control and eliminate the seven most common NTDs. private cooperation aimed at achieving greater scale and systemic impact than could be achieved alone. In 2014, the AbbVie Foundation began its partnership with the Sabin Vaccine Institute on two initiatives in Latin America Over the course of the study, a key goal and outcome has with the goal of making a positive impact on finding, been to build local capacity. For example, more than 120 educating, testing, linking and treating some of the poorest public health and lab technicians have been trained to take people impacted by NTDs in the region. samples for analysis from 500 children in 10 Mexican states, for a target sample of 5,000 to be tested for STH and malaria. Fighting soil-transmitted helminths in A basic assessment of water and sanitation facilities at From 2014 to 2015 AbbVie’s funds helped catalyze NTD participating schools is also being conducted. The research efforts working with Sabin’s Global Network for Neglected findings will contribute to disease surveillance efforts in Tropical Diseases alongside a Colombian organization called Mexico, as well as inform future NTD interventions. Sinergias (Estratégicas para la Salud y el Desarrollo Social),

28 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

5.3 Convening public health officials and academics Participating in multi-stakeholder policy In addition to supporting community-driven health programs, 6and advocacy platforms local and national capacity building and independent impact assessments, another role that corporate foundations can play No matter how much is being done by individual companies, is to support forums that enable dialogue between health governments, and research organizations or even disease- experts, policy makers and funders. specific product development partnerships to discover, develop and deliver effective and affordable treatments In September 2015, for example, the AbbVie Foundation for NTDs, these efforts are necessary but not sufficient. supported a one-day symposium at University’s Baker Collective action and better coordination is also needed Institute for Public Policy, which explored challenges to mobilize additional financial resources and business faced by Mexico and the U.S in handling NTDs, the support, to advocate for greater action by national leaders relationship between public health outcomes and economic in all sectors and influence policy reforms, and to address circumstances, and opportunities to work collaboratively in some of the broader systemic challenges of health systems shaping public policy to combat these diseases. The event strengthening. was entitled, “The United States and Mexico: Addressing a Shared Legacy of Neglected Tropical Diseases and Poverty.” Over the past decade a number of multi-stakeholder platforms have been convened around achieving these The conference was organized in collaboration with Baker objectives. They include initiatives such as Uniting to Combat Institute’s Center for Health and Biosciences and the Mexico NTDs, the END Fund, the Global Network for Neglected Center, as well as the END FUND, the National School of Tropical Diseases, the Coalition for Operational Research Tropical Medicine at Baylor College of Medicine, and the on NTDs, the NTD Non-Governmental Development Texas Children’s Hospital Center for Vaccine Development. Organizations Network, and the CEO Roundtable convened The convening power of these diverse organizations by the Bill & Melinda Gates Foundation (BMGF) as well as that span the public policy, public health and economic the increasingly proactive coordinating role on NTDs played development agendas, enabled the conference to attract by WHO over the past decade. In many cases the PDPs senior policy makers from both countries as well as academic, described earlier in the case study are active participants in civil society, philanthropic and medical leaders. Deliverables the platforms, alongside individual companies, other UN and from the conference, include a policy report based on donor agencies, foundations, governments and universities. symposium findings and a series of articles highlighting different NTDs impacting the two countries. 6.1 The CEO Roundtable From a business perspective, the Gates CEO Roundtable, The examples outlined above, ranging from community- which was first convened in 2009, has been a valuable driven projects to public policy dialogues, illustrate the platform for mobilizing collective action and new models contribution that can be made by a corporate foundation. of partnership. The BMGF’s strategy in global health is to, They show how the AbbVie Foundation is working with “harness advances in science and technology to save lives nonprofit partners—from delivery focused NGOs to academic in developing countries. [It] works with partners to deliver and research institutions—and with public sector institutions proven tools—including vaccines, drugs, and diagnostics— to convene dialogues, support research, and enhance as well as to discover path-breaking new solutions that are community-based health delivery, capacity building and affordable and reliable.”26 The CEO Roundtable was convened evaluation of NTD programs. There is growing potential for by to proactively engage senior executives and corporate foundations to take this systemic type of approach scientists from some of the world’s leading pharmaceutical to help strengthen health systems in resource-constrained companies in a joint effort to improve the health of the contexts. world’s poorest people. There are currently three work streams: Neglected Tropical Diseases; Tuberculosis; and Access and Affordability. In addition to these work streams,

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 29 II ABBVIE’S ENGAGEMENT IN TACKLING NTDS

participants in the CEO Roundtable have agreed on three 6.2 The London Declaration on Neglected Tropical cross-cutting objectives: Diseases • To accelerate R&D for priority new drugs, vaccines and Another important milestone in the growing momentum diagnostics to tackle NTDs was achieved on January 30th, 2012. • To deliver and enhance access to priority medicines in Under the leadership of the World Health Organisation developing countries (WHO) and Uniting to Combat NTDs, the following group • To enhance awareness and resource mobilization through of pharmaceutical companies, public donors, private advocacy, knowledge-sharing and information exchange. foundations and NGOs came together to endorse The London Declaration on Neglected Tropical Diseases:27 The Gates CEO Roundtable is itself a good example of the power of individual leadership and the vital convening AbbVie • AstraZeneca • Bayer • Becton Dickinson • role that a foundation such as the BMGF can play. It would Bill & Melinda Gates Foundation • Bristol-Myers have been difficult for an individual corporate CEO to bring Squibb • Children’s Investment Fund Foundation • together his or her peers and competitors around the topic UK Department for International Development (DFID) of neglected diseases. It would have been unlikely that any • Drugs for Neglected Diseases initiative • Eisai • Gilead of the nonprofit research organizations, at that time mostly • GlaxoSmithKline • Johnson & Johnson • Lions Club at a fledgling stage in their existence, would have had the International • Merck KGaA • Merck & Co. Inc. (MSD) • status and convening power to get CEOs of the world’s major • Novartis • Pfizer • Sanofi • United States pharmaceutical companies around the same table. Bill Gates Agency for International Development (USAID) • used his personal convening power and the platform of the the World Bank. foundation to enable the initial dialogue to happen. The London Declaration is a public statement that sets out Throughout the process, the BGMF has continued to provide clear goals and specific commitments from the participants strong advocacy support for the potential of science and aimed at scaling up the level of collaboration needed to technology, financial support, the expertise of its own global control, eliminate or eradicate 10 of the 17 major NTDs by health team, and the neutral convening space and structure 2020. It has led to targeted working groups and a transparent that is needed for continued dialogue, trust building and process of reporting progress against the commitments emerging collaboration to take place. At the same time, many made, and illustrates the potential for non-competitive of the participating organizations have strengthened their collaboration towards improving public health in some own bilateral relationships and partnerships. of the world’s poorest communities.

Early discussions were structured to include not only company CEOs, but also scientists from the companies and the nonprofit research organizations, in the context of one of the Roundtable’s working groups. This in turn led to the generation of specific project ideas and partnerships, and the building of trust and shared commitment that has been essential in making them work. Initiatives such as the TB Drug Accelerator have taken joint efforts to a new level of shared resources and commitment, and AbbVie has participated from the outset.

30 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE III Conclusion and lessons learned

This case study has aimed to illustrate some of institutional, deeply on the skills, expertise and networks that they have individual and collective leadership that has been built through these jobs. undertaken by one company and some of its scientists, managers and external partners to support effective product · Building collective leadership – making a commitment development partnerships as well as community-based to work in non-traditional ways with non-traditional health programs, and public advocacy and awareness- partners through product development partnerships, raising in this field of NTDs. In this particular example, the community-based programs, and multi-stakeholder company does not currently have a commercial business in alliances and platforms that serve to coordinate resources the NTD drugs and treatments that it is addressing through and capabilities, and leverage impact and influence its external partnerships and no relevant drugs to donate, but is focused on sharing the skills, expertise and time of some of Some key lessons from both the internal coordination within its leading scientists, as well as sharing relevant compounds AbbVie and its external partnerships are as follows: and supporting program enhancement through providing pro bono laboratory platforms and tests where relevant. Leverage core expertise and capabilities 1 Even when a company does not have a direct business As of early 2016, AbbVie had shared more than 120,000 interest or commercial imperative to engage in partnerships compounds with nonprofit research partners, and hundreds aimed at tackling a global health or sustainable development of scientific tests had been undertaken in the company’s challenge, it can still make a valuable contribution through laboratories on their behalf. Over the past several years engaging the skills and passions of its employees and other some 160 AbbVie scientists have been working in the relevant corporate capabilities and assets. As Dr. Kempf company’s neglected diseases effort, with support from the concludes, “There is a tremendous desire within the industry company’s senior executives, and managers in its corporate to make a difference in the world. That is why we took these responsibility, government affairs and technology licensing jobs. The volunteer NTD program gives our scientists an and collaborations teams. It has engaged in a number of opportunity to do something extra to make a difference—to product development partnerships, most notably with the make a real impact. The response by the scientists at AbbVie Drugs for Neglected Diseases initiative (DNDi), Medicines has been overwhelming.”28 All companies have core expertise for Malaria Venture (MMV), TB Alliance and TB Drug and capabilities that can be creatively leveraged to support Accelerator (TBDA), Anti-Wolbachia Consortium (A-WOL), global goals in a way that either directly or indirectly benefits and Macrofilaricidal Drug Accelerator (MacDA). These the company and its employees. collaborative efforts are ongoing, both internally and externally. Sustain senior executive support 2The AbbVie Neglected Diseases initiative is led by The example illustrates the potential of: its scientists, but relies on the sustained support of the company’s senior executives. Almost all successful initiatives · Strengthening institutional leadership – inside where companies are engaged in supporting global companies through setting up a cross-functional goals—whether through their core business operations and leadership council; prioritizing key diseases or geographies products, the skills and time of their employees, or their through dialogue and alignment between R&D and philanthropic contributions—require clear and ongoing corporate responsibility strategies; and coordinating senior executive leadership. In some cases, it is the CEO or different research and functional teams to work effectively other senior executives who take the lead, both internally and together on an essentially pro bono basis. externally. In many situations, the senior executives create the enabling environment for their employees to take a lead, · Harnessing individual leadership – from scientists and and a small group of relevant experts or managers emerge functional managers, encouraging them to engage in as champions for a particular company-wide initiative. If such initiatives beyond their “day-jobs”, which nonetheless draw initiatives are not recognized and supported by the CEO

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 31 III CONCLUSION AND LESSONS LEARNED

and other senior executives, it is difficult if not impossible essential—as the scientists or technical experts in for-profit, for them to be sustained over the long-term. This support nonprofit and public institutions are more likely to share a is even more important when there is no direct commercial common language. As Dr. Kempf comments, “The scientists benefit or products involved in the program. in most of our partners—such as DNDi, MMV and TB Alliance —have worked in the pharma industry and understand the Think outside institutional silos significant challenges of developing a new drug. We speak 3In many companies and other large institutions, people a common language and share a common approach that tend to stay within their organizational and operational contributes greatly to moving forward more rapidly.”30 boundaries—working within their own teams and divisions, Even in cases like this, however, time and effort needs with little incentive or even permission to build professional to be invested in building trust and strong relationships. relationships across these boundaries. AbbVie’s example illustrates the potential to build cross-boundary structures Explore opportunities for non-competitive and relationships that can enhance team-building and 5industry collaboration cooperation in a way that ‘business as usual’ would struggle It is often difficult for competitors to work together, to achieve. The Executive Council on Neglected Diseases has regardless of industry sector, and yet some of the greatest given the company a cross-functional structure or platform advances in addressing systemic global health and for its program, but even more valuable has been the day- sustainable development challenges can come from to-day cooperation that has emerged, both within the R&D non-competitive coalitions. Often, a neutral convener or division and between this and other parts of the company. backbone organization plays an essential role in bringing Dr. Kempf observes, “Generally, our NTD program operates companies together.31 In this particular case, for example, in a decentralized fashion. But through informal networking working with the Gates CEO Roundtable has created the we are able to bring a lot of people from different scientific platform for various company scientists to join in several backgrounds together to produce substantial collective fruitful partnerships, both with each other as well as impact.” 29 nonprofit and public sector partners.

Take time to build trust and shared The TB Drug Accelerator model is an experiment in 4understanding with external partners which companies are sharing information in a The types of multi-sector product development partnerships non-competitive fashion to develop new antibiotics. profiled in this case study demonstrate relatively new This approach could be applied to other challenges, within approaches to addressing market failures, governance the global health field and beyond—for example in areas gaps and other obstacles to achieving global goals. such as , financial inclusion, small enterprise The core rationale of such partnerships is to leverage diverse development, energy access, clean water and sanitation. resources and capabilities in order to tackle an issue more cost-effectively, rapidly, systemically or equitably than any Undertake rigorous measurement of projects one organization or sector can address alone. The power of 6As with any project or program, what gets measured the partnership is in the diversity of the partners. Yet, such gets managed. There is an ongoing challenge in the fields of diversity often means that the participating individuals and global health and sustainable development to measure not organizations speak ‘different languages’, have different only inputs and outputs, but also impacts and outcomes. motives, different incentives and even different time This is difficult to do even when only one organization is horizons. involved and even more challenging in the case of multi- stakeholder partnerships with multiple contributions As such, intermediary leaders are often needed to facilitate and interventions. At the same time, in the field of drug the collaboration, build trust, strengthen discovery and development, there are clear and well-tested and clarify roles and responsibilities. This role is probably less metrics to evaluate results of the actual R&D process, and a crucial in situations where technical or scientific expertise is growing body of empirical analysis on assessing affordability,

32 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE III CONCLUSION AND LESSONS LEARNED Conclusion

accessibility and sustainability of delivery and treatment These lessons are relevant not only in initiatives and regimens. Collaborative efforts can play a valuable role partnerships aimed at tackling NTDs and improving in further improving metrics and communicating results global health, but in any effort to achieve the sustainable of these evolving product development and delivery development goals. partnerships. The shared goal of combating NTDs to improve the health Encourage values-based and multi-disciplinary and economic prospects of over a billion of the world’s 7leadership poorest people remains a complex and daunting one. One of the clearest lessons that come out of this case study Efforts to discover, develop and deliver new drugs and and similar ones is the crucial importance of values-based implement more collaborative approaches will take years, leadership and actively encouraging diverse disciplines, not months. functions and perspectives. Current leaders—be they at the top of the organization or leading a pro bono program, Governments must take a lead, but companies and nonprofit must create an environment where everyone is encouraged organizations also have an important role to play, especially to build so-called ‘soft skills’. These include the ability to those with scientific and technological expertise. Individuals collaborate and work as a team, especially across silos, like Dr. Dale Kempf, Dr. Kennan Marsh, Dr. Tom von Geldern, respect for and ability to embrace diversity of skills and and their fellow scientists play a vital role within their experiences, personal integrity and accountability for companies to advance these efforts. By partnering with results alongside a willingness to share credit, and a governments, universities, and other public and non-profit commitment to creating communities of practice, both health organizations as well as their peers and competitors, within and external to the organization. these companies can enable their scientists to leverage world-class technical expertise for the public good, whether The ability of current leaders to model these behaviors, while on a pro bono basis, as in this example, or commercially or also emphasizing the importance of domain expertise, such through hybrid models that combine both private and public as scientific, technical and managerial skills is a key factor in sector resources. determining the success of business partnerships that aim to support global goals. And they are a key determinant for As Dr. Kempf concludes, “Only through committed long-term building respectful and productive working relationships and partnerships will we be likely to achieve significant victories organizations more generally. against diseases that have devastated humankind for too long”.32 Such long-term partnerships are not easy to create. They are even more challenging to sustain. Yet, they offer one of the best hopes we have in today’s world, not only for tackling neglected diseases, but for fighting inequality and injustice and improving the quality of peoples’ lives more broadly.

SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE 33 METHODOLOGY AND ACKNOWLEDGMENTS

This case study is not intended to be a program evaluation or company employees meet with students to discuss dilemmas impact assessment. It is a descriptive overview of some of the and opportunities in the field of responsible business practices, institutional, individual and collective leadership mechanisms global health and global development. The initiative and that are being used by one company and some of its leading our students also undertake research and learn from these scientists and managers to collaborate internally and with companies and their public sector and nonprofit partners, external product development partnerships, humanitarian while making every effort to ensure independence of thinking, organizations and universities to support a broader global effort analysis and recommendations. aimed at combating neglected tropical diseases. And to do so in a situation where the company in question does not have We are grateful for the participation of some of AbbVie’s senior a commercial business focused on discovering, developing or scientists and for the time they have given us to share their delivering treatments for these diseases. The case study is based views and to educate us on some of the challenges, as well as on in-person interviews, review of internal documents and desk- the potential of drug discovery and development in the case of based research of publicly available materials on NTDs, NTDs. In particular, we would like to acknowledge Dr. Dale and product development partnerships. Kempf, Dr. Kennan Marsh, Dr. Tom von Geldern and Dr. Jeffrey Rohde. Thanks also to Tracie Haas, Katharine Jensen, David AbbVie was selected as the topic of the case study in its capacity Schaffer, Christopher Lynch, Veronica Arroyave and Jeff as one of the companies that participate in the Corporate Richardson for their input and feedback. And to Kari Straus at Responsibility Initiative at Harvard Kennedy School. This the University of Wisconsin-Madison and the teams at DNDi, participation includes the provision of funding for student MMV, TBDA, and A-WOL. At Harvard Kennedy School thanks to engagement, research and policy outreach activities, and Justin Miletti and Scott Leland for supporting research and participation in a Visiting Practioners Program whereby administration and to Alison Beanland who designed the report.

ENDNOTES

1 Speech made by UN Secretary-General, Ban http://www.globalnetwork.org/sustainable- 23 The A-WOL Consortium. Why Anti- Ki-moon to special event on Philanthropy development-goals-must-tackle-neglected- Wolbachia? www.a-wol.com. Accessed March and the Global Public Health Agenda, New tropical-diseases 20, 2016 York, 23 February 2009 8 Interview with Dr. Dale Kempf on July 29, 24 AbbVie Foundation mission statement 2 Peter J. Hotez, Alan Fenwick, Lorenzo Savioli 2015 25 Morillo, Carlos A., et. al. October 2015. New and David H. Molyneux. Rescuing the bottom 9 Ibid. England Journal of Medicine, V373(14): billion through control of neglected tropical 10 Ibid. 1295-1306. DOI: 10.1056/NEJMoa1507574. diseases. The Lancet. Lancet 2009: 373: 1570-75 http://www.nejm.org/doi/full/10.1056/ 11 DNDi. An innovative approach to R&D for 3 For more details on the Sustainable NEJMoa1507574 Neglected Patients: Ten years of experience and Development Goals see: https:// lessons learned by DNDi. December 2013 26 The Bill and Melinda Gates Foundation. sustainabledevelopment. What We Do. http://www.gatesfoundation. 12 Interview with Dr. Dale Kempf on July 29, un.org/?menu=1300 org/What-We-Do/Global-Health/Neglected- 2015 4 Centers for Disease Control and Prevention Tropical-Diseases (Accessed March 14, 2016) 13 Details on these diseases are sourced from (CDC). Neglected Tropical Diseases. http:// 27 Full details of the London Declaration can “New Hope for Neglected Patients”, Drugs for www.cdc.gov/globalhealth/ntd/ (Accessed be found on http://unitingtocombatntds. Neglected Diseases initiative presentation August 25, 2015) org/resource/london-declaration. (accessed brochure. http://www.dndi.org/about-dndi/ 5 World Health Organisation (WHO). Why are March 22, 2016) Accessed March 14, 2016. some tropical diseases called “neglected”? 28 Dr. Dale Kempf. Written feedback to 14 Statistics from the Medicines for Malaria January 2012. http://www.who.int/features/ questions. March 3, 2016 qa/58/en/. (Accessed August 25, 2015) Venture website. http://www.mmv.org/ malaria-medicines. Accessed March 14, 2016. 29 Ibid. 6 http://blogs.plos.org/ thestudentblog/2015/01/01/neglected- 15 Ibid. 30 Ibid. 16 Ibid. tropical-diseases-challenges-post-2015- 31 FSG has done groundbreaking work on development-era/. Rachel Cotton is pursuing 17 Ibid. the role of collective impact and backbone her PhD in Immunology at Harvard, and 18 World Health Organisation. Global organizations. See www.fsg.org for more is interested in global health, infectious Tuberculosis Report, 2015 details. disease, and science policy. She graduated 19 The TB Alliance. Our Mission. www.tballiance. from the University of Notre Dame, where 32 Interview with Dr. Dale Kempf on July 29, org Accessed March 20, 2016 she was Editor-in-Chief of the undergraduate 2015 research journal, Scientia 20 Ibid. 7 Hotez, Peter and Neeraj Mistry. Sustainable 21 The A-Wol Consortium. Target Diseases. Development Goals Must Tackle Neglected www.a-wol.com/target-diseases/. Accessed Tropical Diseases. Global Network on March 20, 2016 Neglected Tropical Diseases. August 12, 2015. 22 Ibid.

34 SUPPORTING RESEARCH IN NEGLECTED TROPICAL DISEASES • LESSONS FROM ABBVIE’S NEGLECTED DISEASES INITIATIVE About the Corporate Responsibility Initiative (CRI)

The Corporate Responsibility Initiative (CRI) at the Harvard Kennedy School’s Mossavar-Rahmani Center for Business and Government (M-RCBG) is a multi- disciplinary and multi-stakeholder program that seeks to study and enhance the public contributions of private enterprise. The initiative explores the intersection of corporate responsibility, corporate governance, and public policy, with a focus on analyzing institutional innovations that help to implement the corporate responsibility to respect human rights, enhance governance and accountability and achieve key international development goals. It bridges theory and practice, builds leadership skills, and supports constructive dialogue and collaboration among business, government, civil society and academics. Founded in 2004, the CR Initiative works with a small Corporate Leadership Group consisting of global companies that are leaders in the fields of corporate responsibility, sustainability or creating shared value. The Initiative also works with other leading corporate responsibility and sustainability organizations, government bodies, non-governmental organizations, foundations and companies to leverage innovative policy research and examples of good practice in this field. Corporate Responsibility Initiative Harvard Kennedy School 79 John F. Kennedy Street Cambridge, MA 02138 USA

CRInitiative.org. www.hks.harvard.edu/centers/mrcbg/programs/cri