Global Portfolio of Antimalarial Medicines Research Translational Product development Access Lead optimization Human volunteers Patient exploratory Patient confirmatory Regulatory review Preclinical Post approval DHODH UTSW/UW/Monash 1 project Novartis P218 (Biotec) MMV048 UCT/TIA OZ439/PQP Sanofi Tafenoquine GSK Rectal Artesunate * Cipla/Strides/WHO-TDR Artemether- lumefantrine Dispersible Novartis 1 Open Source Drug Discovery Univ. Sydney 2 projects GSK SJ733 St Jude/Eisai ACT840 Actelion OZ439/FQ Sanofi Dihydroartemisinin piperaquine Paediatric Sigma-Tau Arterolane/PQP Ranbaxy * * Artesunate for injection Guilin 2 Heterocycles UCT Orthologue Leads Sanofi DDD498 Merck Serono (Univ. Dundee) CDRI 9778 Ipca Dihydro-artemisinin- piperaquine Sigma-Tau KAE609 Novartis Co-trimoxazole ITM Antwerp 3 Diversity Oriented Synthesis Broad/Eisai Tetraoxanes LSTM/Liverpool PA92 (Drexel/UW/GNF) N tert butyl Isoquine LSTM/Liverpool/GSK Artemisinin Naphthoquine * * KPC Pyronaridine- artesunate Shin Poong KAF156 Novartis 4 dUTPase Inhibitors Medivir Whole cell St Jude/Rutgers/USF MMV253 (AstraZeneca) Artemether sub-lingual spray PhotoPharma Ltd Artesunate- amodiaquine * Sanofi/ DNDi DSM265 Takeda 5 Imidazolidine diones WRAIR Heterocycles Celgene GSK030 GSK Artesunate- Mefloquine * Cipla/DNDi Fosmidomycin Piperaquine Jomaa Pharma/GmbH Pf NDH2 Imperial College London Pf NMT Imperial College London DSM421 (UTSW/UW/ Monash) Methylene Blue/AQ Heidelberg SPAQ * Guilin 6 Pantothenamides TropIQ/Pansynt TI Pharma AN13762 Anacor SAR97276 Sanofi Pyronaridine- Artesunate Paediatric Shin Poong NPC1161B Mississippi Artemisone UHKST JPC2997 Jacobus AQ13 Immtech MK4815 Merck DF02 Dilafor Footnotes: Brand names 1: Coartem® Dispersible; 2: Artesun®; 3: Euratesim®; 4: Pyramax®; 5: CoarsucamTM ASAQ/Winthrop®; 6: SPAQ-COTM

Description Target Product Profiles and Target Candidate Profiles: The malaria community has defined two Target Product Profiles (TPPs) for medicines to make eradication achievable: TPP1: a treatment combination that is ideally a Single Exposure Radical cure and Prophylaxis (SERCaP) and TPP2: Single Exposure Chemoprotection (SEC). 3 day treatment products – TPP1 ❯ Artemether-lumefantrine dispersible (Coartem® Dispersible), generic by Ajanta ❯ Dihydroartemisinin-piperaquine (Eurartesim®) ❯ Dihydroartemisinin-piperaquine paediatric (Eurartesim®) ❯ Pyronaridine-artesunate (Pyramax®) ❯ Pyronaridine-artesunate paediatric (Pyramax®) ❯ Artesunate-amodiaquine (CoarsucamTM, ASAQ/Winthrop®) FDC generics by Ajanta, Ipca, Guilin and co-blistered generics by Strides & Cipla ❯ Artesunate-mefloquine, co-blistered generic by Acino/Mepha New compounds to contribute to SERCAP or MERCAP (Multiple exposure radical cure prophylaxis) – TPP1 Seasonal malaria chemoprevention ❯ Sulfadoxine-pyrimethamine + amodiaquine (SP+AQ) Severe malaria ❯ Rectal artesunate ❯ Artesunate for injection (Artesun®) Relapse prevention ❯ Tafenoquine To develop the individual compounds for combination into the TPPs, MMV has defined five Target Candidate Profiles (TCPs): Asexual blood stage activity (TCP1,2) Relapse prevention (TCP3a) Transmission reduction (gametocytocidal or sporontocidal) (TCP3b) Chemoprevention (TCP4) Brought into portfolio after approval. Collaboration with DNDi No progress report in the last two years Pending review or approval by WHO Prequalification, or by regulatory bodies who are ICH members or observers Approved in several countries but not approved by SRA nor WHO prequal * * *