European & Developing Countries Clinical Trials Partnership (EDCTP) Towards EDCTP2 22 July 2014 Melbourne, Australia Ole F. Olesen, Ph.D., HD Director of North-North Cooperation, EDCTP, The Netherlands

Justification for EDCTP2 Objectives Clinical development of effective, safe, accessible, suitable and affordable medical interventions for poverty related and neglected diseases (PRNID) in partnership with sub-Saharan African countries Problem No economic incentive for private investments in PRNID Public investments are sparse and fragmented Know-how is fragmented Background EDCTP-1: EDCTP-2:

Who we are Participating States 13 European Countries Austria, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain and United Kingdom 9 African Countries Cameroon, Congo, Ghana, Mozambique, Senegal, South Africa, Tanzania, Uganda, Zambia Countries that can receive funding All sub-Saharan African countries All EU Member States and Associated Countries

Governance Public-Public Partnership between sovereign states Operates as an independent legal entity Owned by the Participating States “Membership fee” of 200,000 EUR/year General Assembly (1 Member from each Participating State) Board (5 Members) EDCTP Secretariat (Hague, NL + Cape Town, ZA) Scientific Advisory Committee (SAC, 16 Members) advice

How it operates 5 5 >683 M € 683 M € >500 M € Industry, other funders, NGO’s, like-minded organisations, Clinical Trials in Africa on PRNID Capacity for Clinical Trials in Africa

What we do Diseases: HIV/AIDS, TB, Malaria and NIDs New tools and interventions: Diagnostics, drugs, vaccines and microbicides Capacity Development: Fellowships, Networks, Ethics, Regulatory

EDCTP in a nutshell Number of projects institutions participate and receiving funds from EDCTP 3442 posts are supported on EDCTP grants Clinical trials Training of scientists Publications - 485

Funding for HIV: Clinical trial Non-clinical trial Clinical trial (€ ‘000) Non trial (€ ‘000) Diagnostics-€ 291 Microbicides€ 2,455€ 6,932 Treatment*€ 28,880€ 419 Vaccines€ 12,753€ 10,633 Other**-€ 4,051 Total€ 44,088€ 22,326 *Including € 5.85 million of funding to support projects on prevention of mother-to-child transmission **Including immunology, epidemiology and cross- cutting issues.

HIV/AIDS activities 54 research projects in 23 sub-Saharan Africa countries

Highlights of selected projects CHAPAS-1: contributed to the evidence base that led to FDA approval and WHO prequalification of PEDIMUNE, a fixed-dose combination formulation for the treatment of HIV in children CHAPAS-3: evaluates three fixed-dose combination first-line antiretroviral drugs Kesho Bora: Influenced revision of 2010 WHO guidelines on PMTCT: 43% reduction in HIV infections in infants and >50% reduction of PMTCT PROMISE-PEP: Prevention of mother to child transmission of HIV1 during 12 months of breastfeeding TaMoVac: Demonstrated that the prime/boost HIV-1 DNA multigene/multiclade-MVA/CMDR vaccine is safe and highly immunogenic when administered intradermally HIV-TB Pharmagene: demonstrated that there is no need to increase efavirenz dose during concomitant rifampicin based anti-TB therapy PRO2000: showed the microbicide was safe (but not efficacious)

How does it work? Calls for proposals for Integrated Projects (Selected, funded and managed by EDCTP Secretariat) National calls for proposals (Selected, funded and managed by PSs according to national rules) Annual Work Plan with call topics Thematic Stakeholder meetings (5 in 2013); Scientific advisory Committee; Commissioned studies, other input First EDCTP2 work plan in August 2014 (tbc)

Integrated Activities Consortia of 2 European PS and 1 sub- Saharan African country (minimum) Grants to individuals: Career development, Senior, Industry, Regulatory, other 1.Clinical Trials (collaborative research) 2. Fellowships 3. Capacity Support Broad non-prescriptive topics, bottom-up Either full funding (100% of costs) or co- funding (up to 33%) with other funders 100% funding Individual institutions or consortia for ethics, training, networking and regulatory activities 100% funding

Thank you The power of sharing science

Example: Phase 2 trial of Example: Phase 2 trial of Malaria vaccine candidate GMZ2: Hybrid of glutamate-rich protein and MSP3 + Alum Targeting the blood stage of the malaria parasite 4 clinical trials sites: CNRFP (Burkina Faso); Makarere (Uganda); Albert Schweitzer Hospital (Gabon); Navrongo (Ghana) 2 European partners: SSI (Denmark); Tubingen University (Germany) 1747 children received 3 doses of 100 microgram or rabies vx Close-out: Feb 2014 Total budget: EUR 6.6 M (from EDCTP)

How does it work? 1.Integrated Activities 2. Participating States’ Initiated Activities 3. Joint Actions with third parties (JA3s) Participation of at least 2 European Participating States and 1 sub-Saharan African country (collaborators from other EU countries can also participate) Selected and managed by EDCTP Funding: 100% (+25% overhead) Projects up to EUR 15 M Selected, funded and managed by PSs according to national rules Funding: 33% EDCTP + 66% PS Co-funding of large activities with other funders Funding: <~25% from EDCTP Annual Work Plan with call topics First EDCTP2 in July 2014 (tbc)

EDCTP Regional Networks of Excellence for clinical trials Western Africa: WANETAM Website: Burkina Faso The Gambia Ghana Guinea-Bissau Mali Nigeria Senegal United States Southern Africa: TESA Website: Botswana Malawi Mozambique South Africa Zambia Zimbabwe France Germany Netherlands United Kingdom Eastern Africa: EACCR Website: Kenya Sudan Ethiopia Tanzania Uganda Germany Sweden United Kingdom United States Central Africa: CANTAM Website: Cameroon Congo, Republic of the Gabon France Germany Strengthening of capacity for clinical trials Addressing inequality Proliferation and sharing of expertise and facilities 64 institutions in 21 African countries Offered short- and long-term training to 1000 researchers Leveraged additional € 24 M Published 38 peer- reviewed papers

Achievements of EDCTP funded grants FDC paediatric formulation: contributed to the evidence base that led FDA approval and WHO prequalification of a fixed-drug combination formulation for the treatment of HIV in children (CHAPAS trial) Influenced revision of 2010 WHO guidelines on PMTCT: 43% reduction in HIV infections in infants and >50% reduction of PMTCT (Kesho Bora) Informed national policy for the treatment of severe malaria: 3 novel ACT drugs were found to be safe and efficacious in treating children with uncomplicated malaria (4ABC study) Establishment of four Regional Networks of Excellence for Conducting Clinical Trials (NoE): the Central African Network for Tuberculosis, HIV/ AIDS and Malaria (CANTAM); the East African Consortium for Clinical Research(EACCR); the Trials of Excellence for Southern Africa (TESA); and the West African Network for TB, AIDS and malaria (WANETAM) Establishment of the Pan-African Clinical Trials Registry (PACTR, which is the only WHO-endorsed primary registry in Africa.

Thematic project funding: Area Intervention

HIV/AIDS projects supported by EDCTP HIV clinical trials PMTCT (pregnancy and breastfeeding) and paediatric treatment – 9 trials Nutritional support for patients starting on ARVs – 1 trial TB/HIV co-infection – 1 trial Microbicides - 3 trials HIV vaccine – 7 trials Adherence to ART – 2 trials Evaluation of antiretroviral drugs - 7 trials HIV/aids capacity building (16 projects) Feasibility studies in preparation for clinical trials (e.g. preparing for phase III vaginal microbicide trials in Rwanda and Kenya) Community and adolescent involvement (e.g. exploring attitudes towards participation in clinical trials) Establish baseline ranges of biomarkers (e.g. Related to vaginal environment in women targeted for microbicide trials) Epidemiological studies – site characterisation

Funding mechanisms Minimum requirement: participation of at least 2 European Participating States and 1 sub-Saharan African country (collaborators from other EU countries can also participate) Integrated Activities: selected and managed by EDCTP Funding: 100% (+25% overhead) Participating States’ Initiated Activities: selected, funded and managed by Participating States according to national rules PSIA cofund: 33% EDCTP and 67% PSs Joint Activities: cofunding of strategic activities with other funders Funding: up to 33% from EDCTP

Public-Public Partnership Operates as an independent legal entity (offices based in the Netherlands and South Africa) Financial and structural support to phase I to IV clinical trials in sub-Saharan Africa EDCTP2 will operate from (part of H2020) The second EDCTP programme (EDCTP2)