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BVGH - Who We Are - BIO Ventures for Global Health
Neglected Disease Pipeline > Diseases > Malaria Background Global Burden | Causative Agents & Transmission | Pathogenesis | Current Control Strategy | Existing Products | Get Involved What is Malaria? Malaria is a parasitic disease that is transmitted by infected mosquitoes. The non-specific nature of the symptoms of uncomplicated malaria, including fever, chills, sweating, body aches, nausea, headache, vomiting, and diarrhea, make clinical diagnosis challenging. In contrast, severe disease rapidly leads to anemia, dehydration, respiratory distress, seizures, and coma. Although severe malaria is easier to identify clinically, the symptoms are difficult to manage in resource poor settings, contributing to a high mortality rate in these patients. When left untreated, uncomplicated malaria can rapidly progress to severe disease, especially in young children. Global Burden Malaria is widespread in the tropical and subtropical regions of Africa, Asia, and Central and South America. There are 108 countries with endemic malaria and an estimated at risk population in high burden countries of close to 670 million.1 Countries with areas of malaria transmission (WHO, 2003) Malaria affects 250 million people per year and results in more than 800,000 deaths.1 Approximately 89% of all malaria deaths occur in Africa, primarily in children under the age of five. In high transmission regions of Africa, malaria accounts for up to 40% of all health expenditures and 30-50% of all hospital admissions.2 The impact of malaria goes beyond health. In Africa, malaria has been estimated to result in more than US$12 billion in lost annual gross domestic profit. It is estimated that in high transmission areas, malaria can decrease GDP by up to 1.3% per year. Back to Top Causative Agent and Transmission Human malaria is caused by protozoan parasites of the genus Plasmodium. There are five species of Plasmodium known to affect man: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. A red blood cell harboring the P. vivax parasite. (photo: CDC/Mae Melvin) Malaria parasite life cycle. Click to view The parasites are transmitted through the bite of an infected female mosquito of the genus Anopheles (usually A. gambiae or A. funestus). A mosquito becomes infected with malaria upon taking a blood meal from an infected person. Under certain stress conditions in the human host, the malaria parasites replicating in the blood differentiate into a sexual stage known as the gametocyte. The gametocyte stage parasites are taken up by the feeding mosquito with a blood meal, undergo sexual replication in the mosquito midgut, and the newly produced sporozoite stage parasites are then transmitted to the next human host when the mosquito takes another blood meal. Pathogenesis Upon taking a blood meal, an infected mosquito injects sporozoite (pre-erythrocytic) stage parasites into the blood stream of the human host. These parasites travel through the body to the liver where they replicate without causing symptoms. After 7-14 days, the parasites burst out of the infected liver cell and enter the bloodstream where they infect red blood cells (erythrocytic stage). The parasites are then able to continuously replicate inside, burst, and reinvade red blood cells. It is the bursting of infected red blood cells as the parasite replicates that leads to the classic periodic fevers and severe anemia associated with malaria. P. falciparum causes the majority of severe disease and mortality associated with malaria (~80%). The severity of P. falciparum malaria is primarily attributed to an unusual physical change that occurs in human red blood cells infected with P. falciparum; the parasite exports its own proteins to the surface of the infected cell causing nearby uninfected red blood cells to stick to the surface of the infected cell. The clumps of infected and uninfected red blood cells are known as rosettes. The rosettes become lodged in the fine capillaries of the organs restricting blood flow. In the brain, this leads to seizures and coma, and in the placenta of a pregnant woman this leads to low birth weight babies or even death of the fetus. P. vivax is less deadly, but worldwide is the most prevalent Plasmodium species. P. vivax is associated with fewer malaria deaths, in part due to the inability of P. vivax to form rosettes. However, P. vivax is in some ways the more challenging species of malaria to control as this species is able to lay dormant in the liver of the human host and reemerge years later. This dormant stage, known as the hypnozoite, is difficult to detect and also difficult to treat. The importance of P. ovale, P. malariae, and P. knowlesi has not been studied extensively. P. malariae and P. ovale are found at a low prevalence in all malaria endemic areas.3 P. knowlesi is a zoonotic species that primarily infects monkeys and was only recently realized as a human pathogen. Research is ongoing to determine the significance of P. knowlesi for human health. Control Strategy The Roll Back Malaria Partnership has set a goal of eliminating malaria in eight to ten countries by 2015.1 Of the 108 malaria endemic countries, 39 are now taking action to move towards elimination.4 As of 2009, nine countries seeking elimination have interrupted transmission.1 As there is no vaccine for malaria, control efforts primarily focus on prevention and treatment in the form of four major activities: 1. 2. 3. 4. Insecticide-treated nets (ITN) Indoor residual spraying (IRS) Accurate diagnosis and treatment with artemisinin combination therapies (ACTs) Intermittent preventive therapy (IPT) during pregnancy Financial support has increased substantially for malaria control programs, rising from US$0.3 billion in 2003 to US$1.7 billion in 2009. However, it is estimated that malaria spending will need to increase to US$5 billion by 2015 in order to sustain current control efforts.1 Back to Top Existing Products Drugs Since 2002, the World Health Organization (WHO) has recommended the use of artemisinin combination therapies (ACTs) for first-line treatment of uncomplicated malaria. This recommendation came as the result of widespread drug resistance to inexpensive monotherapies such as chloroquine and sulfadoxine-pyrimethamine. By combining at least two antimalarials, ACTs reduce the risk for new drug resistance. There are currently five ACTs in use and in late stage development:5 • • • • • Artesunate-amodiaquine (Launched Q4 2008) Artemether-lumefantrine (Launched Q1 2001) Artesunate-mefloquine (Launched Q2 2008) Dihydroartemisinin-piperaquine (Expected launch Q1 2011) Pyronaridine-artesunate (Expected launch Q1 2011) WHO recommends treatment of severe malaria with IV artesunate. However, intramuscular artesunate, artemether, or quinine, and rectal artesunate are recommended for use in settings where IV treatment is not possible. The one exception to the recommended use of ACTs is in pregnancy. Although there are no reports of adverse events due to use of ACTs during the first trimester of pregnancy, quinine is recommended during the first three months pending more detailed studies of the risks of ACT use. ACTs are still recommended for first line treatment during the second and third trimesters. Because of the severe effects malaria can have on the developing fetus, it is also recommended that women receive intermittent preventative therapy with sulfadoxine-pyrimethamine (SP) during their second and third trimesters. Vaccines There is currently no vaccine approved for the prevention of malaria. Diagnostics The high cost of ACTs and the potential for drug resistance has motivated efforts to ensure that ACTs are used correctly. WHO now recommends the use of confirmatory diagnosis for all suspected cases of malaria prior to treatment with ACTs. Unfortunately, malaria diagnosis by microscopy, the gold standard for malaria diagnosis, is not possible in low resource settings. As an alternative, numerous rapid diagnostic tests (RDTs) have been developed to allow minimally trained health workers to administer tests at the point of care. Available RDTs are now being systematically evaluated by WHO/TDR in order to determine which tests are most reliable. Back to Top References 1. WHO (2009) World Malaria Report 2009. 2. WHO, Malaria Fact Sheet. 3. Mueller I et al. (2007) “Plasmodium malariae and Plasmodium ovale – the ‘bashful’ malaria parasites.” TRENDS in Parasitology 23: 278-283. 4. The Malaria Elimination Group (2009) Shrinking the Malaria Map: A prospectus on elimination. 5. Wells TNC et al. (2009) “New medicines to improve control and contribute to the eradication of malaria.” Nature Reviews Drug Discovery 8: 879-891. Get Involved To learn how you can get involved in neglected disease drug, vaccine or diagnostic research and development, or to provide updates, changes, or corrections to the Global Health Primer website, please view our FAQs or contact us at globalhealthprimer@bvgh.org. Pipeline & Analysis Drugs | Vaccines | Diagnostics | Get Involved Drugs PIPELINE Product/Research Program Developers AZCQ London School of Hygiene and Tropical Medicine Medicines for Malaria Venture Pfizer Inc. Arterolane + piperaquine Ranbaxy Laboratories Ltd. Artemisone Hong Kong University of Science and Techology Medicines for Malaria Venture University of Oxford OZ 439 Medicines for Malaria Venture Monash University Swiss Tropical and Public Health Institute University of Nebraska Tinidazole Walter Reed Army Institute of Research Methylene blue + amodiaqine or artesunate Heidelberg University ArTiMist Eastland Medical Systems Ltd HC Berlin Pharma AG ProtoPharma Limited Fosclin Jomaa Pharma N-tert butyl isoquine GlaxoSmithKline Liverpool School of Tropical Medicine 97/78 Central Drug Research Institute Ipca Laboratories Ltd ARCO Chinese Academy of Military Medical Discovery Pre-clinical Phase I Phase II Phase III Sciences GlaxoSmithKline Tafenoquine Medicines for Malaria Venture Walter Reed Army Institute of Research AQ-13 Immtech Pharmaceuticals Inc. Tulane University NITD 609 Medicines for Malaria Venture Novartis Institute for Tropical Diseases Sevuparin Dilafor NPC1161B University of Mississippi RKA 182 University of Liverpool GNF156 Genomics Institute of the Novartis Research Foundation Medicines for Malaria Venture CEM 101 Cempra Pharmaceuticals P218 Medicines for Malaria Venture 4-aminoquinoline derivatives DesignMedix Portland State University 99/411 Central Drug Research Institute Ipca Laboratories Ltd ND-901 NeED Pharma PA1103/SAR116242 Palumed Sanofi-Aventis PMX-30024 and PMX-70008 PolyMedix Inc. Centanamycin McGill University Spirogen Ltd. AN3661 Anacor Pharmaceuticals, Inc. Medicines for Malaria Venture University of California, San Francisco 2-0, 3-0 desulfated heparin (ODSH) ParinGenix, Inc. Advanced Life Sciences Walter Reed Army Restanza Institute of Research Imidazolidinedione analogs Walter Reed Army Institute of Research Cell based screening/lead optimization Pfizer Inc. Special Programme for Research and Training in Tropical Diseases DPAP inhibitors Stanford University University of California, Berkeley Cell based screening/lead identification Merck & Co., Inc. dUTPase inhibitors Medivir Novartis series lead optimization Biomedical Primate Research Centre Medicines for Malaria Venture Novartis AG Novartis Institute for Tropical Diseases Swiss Tropical and Public Health Institute Dihydroorotate dehydrogenase (DHODH) inhibitors Medicines for Malaria Venture Monash University University of Washington UT Southwestern Medical Center Genz-668764 Broad Institute of MIT and Harvard Genzyme Medicines for Malaria Venture SSJ-183 Centre for Drug Candidate Optimisation Swiss Tropical and Public Health Institute Synstar Japan Co., Ltd. Aminopyridines Pyrazoles Centre for Drug Candidate Optimisation Medicines for Malaria Venture Swiss Tropical and Public Health Institute University of Cape Town Drexel University College of Medicine Medicines for Malaria Venture University of Washington Quinolones Centre for Drug Candidate Optimisation Drexel University College of Medicine Medicines for Malaria Venture Oregon Health & Science University University of South Florida Industry screening efforts AstraZeneca Broad Institute of MIT and Harvard Genzyme Novartis AG Pfizer Inc. Sanofi-Aventis Acridones DesignMedix Portland State University Walter Reed Army Institute of Research Hypoestoxide ParaQuest, Inc. Falcpain 2/3 protease inhibitors Amura Therapeutics Ltd. Malaria drug discovery program Eisai Inc. Quinoline Methanol Medicines for Malaria Venture Walter Reed Army Institute of Research Genz DHODH Broad Institute of MIT and Harvard Genzyme Medicines for Malaria Venture ISPA-028 National Institute of Allergy and Infectious Diseases Ferroquine + artesunate Sanofi-Aventis On Hold SAR 97276 Sanofi-Aventis On Hold GSK 932121 GlaxoSmithKline On Hold MK 4815 Medicines for Malaria Venture Merck & Co., Inc. On Hold GlaxoSmithKline GSK 2243979A and GSK 2223413A RNAi therapeutic Medicines for Malaria Venture Alnylam Pharmaceuticals, Inc. Cenix BioScience On Hold On Hold ANALYSIS Despite having numerous products in clinical development, including new chemical entities, the majority of the clinical stage antimalarials are highly related to drugs that are already on market. There are no compounds with novel targets or mechanisms of action in clinical development for malaria. Drug development programs in the preclinical and discovery phases are exploring more diverse targets including: • • • • Lipid biosynthesis inhibitors Nucleic acid synthesis inhibitors Protein synthesis inhibitors Compounds with unknown mechanisms of action from cell-based screening projects The majority of safe medications for malaria target the blood stage of the parasite. However, there is increasing interest in targeting other stages of the parasite lifecycle including the gametocyte stage that is transmitted to the mosquito and the hypnozoite stage of P. vivax that persists in the liver. The persistence of the gametocyte stage following treatment allows infected individuals to transmit malaria to mosquitoes even after receiving treatment, while failure to target the hypnozoite stage can allow parasites to re-emerge from the liver and re-infect the host years after treatment. While these stages of the parasite lifecycle do not cause disease directly, they do pose challenges for malaria control and elimination programs. The 8-aminoquinolines, such as primaquine, are able to kill gametocytes and hypnozoites, but safety concerns in patients with G6PD mutations1 have limited their widespread use. As the target of the 8-aminoquinolines remains unknown, there is a great need to explore new potential targets as well as diverse small molecules to target the gametocytes and hypnozoites. Strengths Weaknesses Opportunities Risks Inability to easily evaluate effects on artemisinin resistant parasites Potentially can overcome artemisinin resistance Unknown if drug candidate will overcome emerging artemisinin resistance ACT market potentially saturated More extensive safety trials in pregnant women Susceptible to same resistance mechanisms as artemisinin Simplified dosing Emergence of artemisinin resistant parasites in Southeast Asia Parasites resistant to many on market products from this class suggesting high risk for resistance to new molecules Primary value will be in combination therapies with other new drugs Existing extensive drug resistance to related molecules Potentially causes hemolysis in patients with G6PD deficiency Identify drug target in order to find alternative inhibitor classes with improved safety New compounds with improved safety could replace this class Synthetic endoperoxides (Artemisinin-related) Most advanced program: Rbx 11160 (in combination with piperaquine), Phase III Based on proven drugs with good potency and safety profiles Aretmisinin derivatives (Artemisinin-related) Most advanced program: On market (Most advanced NCE artemisone, Phase II) Based on proven drugs with good potency and safety profiles 4-aminoquinolines (Chloroquine-related) Most advanced program: On market (Most advanced NCE ferroquine, Phase II) Based on proven drugs with good efficacy and safety profiles 8-aminoquinolines (Target unknown) Most advanced program: On market (Most advanced NCE tafenoquine, Phase I) Targets P. vivax hypnozoites and P. falciparum gametocytes Back to Top Vaccines PIPELINE Product/Research Program Developers RTS,S/AS01 GlaxoSmithKline Malaria Vaccine Initiative NMRC-M3V-Ad-PfCA Naval Medical Research Center Walter Reed Army Institute of Research PfSPZ Malaria Vaccine Initiative Naval Medical Research Center Sanaria, Inc. University of Maryland Center for Vaccine Development PvCSP/AS01 GlaxoSmithKline Malaria Vaccine Initiative Walter Reed Army Institute of Research AdCh63 MSP-1 Imaxio Okairos Srl The Jenner Institute University of Oxford MVA MSP-1 Imaxio Okairos Srl The Jenner Institute University of Oxford AdCh63 AMA-1 Imaxio Okairos Srl The Jenner Institute University of Oxford MVA AMA-1 Imaxio Okairos Srl The Jenner Institute University of Oxford AdCh63 ME-TRAP Imaxio Okairos Srl The Jenner Institute University of Oxford Discovery Pre-clinical Phase I Phase II Phase III MVA ME-TRAP Imaxio Okairos Srl The Jenner Institute University of Oxford DNA-Ad Naval Medical Research Center Vical, Inc. AMA1-C1/Alhydrogel National Institute of Allergy and Infectious Diseases University of Oxford p52-/p36- GAP Vaccine Seattle Biomedical Research Institute Walter Reed Army Institute of Research AdVac Crucell Malaria Vaccine Initiative USAID Malaria Vaccine Development Program GMZ2 African Malaria Network Trust Statens Serum Institut Vakzine Projekt Management GmbH MSP3-LSP African Malaria Network Trust London School of Hygiene and Tropical Medicine PEV301 & 302 Mymetics S.A. Pevion Biotech Ltd. Swiss Tropical and Public Health Institute BSAM-2/Alhydrogel National Institute of Allergy and Infectious Diseases Ichor Medical Systems, EP1300 polyepitope DNA vaccine EBA-175 RII-NG JAIVAC-1 Inc. National Institute of Allergy and Infectious Diseases VaxOnco Baylor College of Medicine National Institute of Allergy and Infectious Diseases Bharat Biotech European Vaccine Initiative International Centre for Genetic Engineering and Biotechnology PvRII International Centre for Genetic Engineering and Biotechnology Malaria Vaccine Initiative AnAPN-1 Johns Hopkins University Medical School Malaria Vaccine Initiative Sabin Vaccine Institute P27A ALMAC Group European Vaccine Initiative Universite de Lausanne CelTOS + GLA-SE Bill & Melinda Gates Foundation Infectious Disease Research Institute US Agency for International Development Walter Reed Army Institute of Research AMA1-DiCo Biomedical Primate Research Centre European Vaccine Initiative Malaria DNA vaccine Avanti Therapeutics NIH/Cytos malaria vaccine research program Cytos Biotechnology National Institutes of Health iBIO malaria vaccine research program iBIO IMX-MSP4 Imaxio University of Oxford PlasProtecT Griffith University pDNA malaria vaccine Inovio Pharmaceuticals, Inc. Malaria Vaccine Initiative University of Pennsylvania Pfs48 Gennova Biopharmaceuticals Malaria Vaccine Initiative Tulane University Pregnancy malaria vaccines National Institute of Allergy and Infectious Diseases Pfs25-EPA/Alhydrogel, Pfs230, Pfs25-Pfs25/Alhydrogel National Institute of Allergy and Infectious Diseases CSP-EPA/Alhydrogel National Institute of Allergy and Infectious Diseases Malaria tSVP National Institute of Allergy and Infectious Diseases Science Applications International Corporation Selecta Biosciences CSVAC European Vaccine Initiative Royal College of Surgeons in Ireland University of Oxford Chimigen malaria vaccine Paladin Biosciences division of Paladin Labs Inc. Toxoplasma KO Vaccine VitamFero CSP Gennova Biopharmaceuticals Malaria Vaccine Initiative AMA1 Malaria Vaccine Initiative Walter and Elizabeth Hall Institute of Medical Research Walter Reed Army Institute of Research EBA/Rh Gennova Biopharmaceuticals Malaria Vaccine Initiative Walter and Elizabeth Hall Institute of Medical Research PvDBII International Centre for Genetic Engineering and Biotechnology Malaria Vaccine Initiative PE selection Malaria Vaccine Initiative Naval Medical Research Center Seattle Biomedical Research Institute FMP010 GlaxoSmithKline US Agency for International Development US Army Medical Research and Materiel Command On Hold ANALYSIS The vaccine development pipeline for malaria is quite diverse and includes multiple technologies and targets covering multiple stages of parasite development. DNA and adenovirus technologies still need to prove themselves in the clinical settings. Therefore, malaria vaccines present the opportunity to validate these new technologies which may in turn help drive forward the vaccine pipeline for other diseases of the developing world. GlaxoSmithKline (GSK) and the Malaria Vaccine Initiative (MVI) are currently conducting a large phase III clinical trial for a recombinant protein-based malaria vaccine called RTS,S or Mosquirix, the most advanced malaria vaccine in development. While this vaccine has only a moderate effect on malaria prevention (~30-50% protection), the real value of the vaccine is most likely in reducing the severity of disease and likelihood of death. The current phase III trial includes 16,000 patients in seven African countries and evaluates effects of vaccination on disease severity as well as prevention. RTS,S/Mosquirix is estimated to be available in 2012. The moderate efficacy of individual vaccines currently in development has caused a shift in development strategy. Moving forward, it is likely that combinations of vaccines will be employed primarily using a heterologous prime-boost strategy. The rationale for this approach is that combinations of vaccines based on different technologies and antigens will provide a more comprehensive immune response to parasite infection. The benefits of combining vaccines include: 1. Combined activation of both humoral and cellular immune responses 2. Ability to target multiple lifecycle stages 3. Possibility to integrate transmission blocking vaccines that block infection of mosquitoes with malaria but have no effect on patient symptoms Strengths Weaknesses Opportunities Risks Combinations with other technologies for prime-boost strategy Due to partial efficacy may need to be used in combination with other vaccines Recombinant protein Species targeted: P. falciparum and P. vivax Stages targeted: pre-erythrocytic, erythrocytic, transmission Most advanced program: RTS,S, Phase III First demonstrated clinical efficacy for malaria prevention (~30-50%) and reduced disease severity Unlikely to provide sterilizing immunity Provides primarily humoral immune response Proven vaccine approach for other diseases Combinations of targets for different stages Additional antigens Additional programs in all stages of development Live attenuated Species targeted: P. falciparum Most similar to natural infection Stages targeted: pre-erythrocytic Preliminary studies using irradiated infected Will require cold chain for delivery/cannot integrate into EPI schedule Additional variations of genetically modified attenuated sporozoites (rather than irradiated Recombinant protein and other technologies with potential EPI integration more advanced and easier Most advanced program: PfSPZ and p52-/p36- GAP Vaccine, Phase II mosquitoes demonstrated sterilizing immunity in small number of patients Proven vaccine approach for other diseases sporozoites) to integrate into general health strategies Apply to P. vivax There are no FDA approved viral vector vaccines on market Preliminary clinical trial evidence from Sanaria not promising Vaccine production extremely labor intensive Cannot apply to P. vivax or other life cycle stages Viral vector Species targeted: P. falciparum Expected to elicit both humoral and cellular immune responses Stages targeted: pre-erythrocytic, erythrocytic Poor immunogenicity alone Vaccine technology not yet proven for any disease Combinations with other technologies for prime-boost strategy Explore additional viral vectors Most advanced program: Numerous programs, Phase II Termination of adenovirus-based HIV vaccine trial in 2005 raised safety concerns which may lead to increased regulatory scrutiny Additional program in phase I development DNA Species targeted: P. falciparum Stages targeted: pre-erythrocytic, erythrocytic Most advanced program: EP1300 polyepitope, Phase II Expected to elicit both humoral and cellular immune responses Poor immunogenicity alone Vaccine technology not yet proven for any disease Apply to P. vivax Combinations with other technologies for prime-boost strategy There are no FDA approved viral vector vaccines on market Explore additional DNA vectors and delivery technologies Back to Top Diagnostics Although there are numerous simple lateral flow RDTs for the diagnosis of malaria available, these tests have had variable effects on the correct use of ACTs. A primary problem identified thus far is that when an RDT result for malaria is negative, a minimally trained health worker can do little in terms of identifying alternative diagnoses and courses of treatment. In a few small clinical trials where field performance of RDTs was evaluated, it was observed that treatment regimens were either, 1) unchanged and ACTs were distributed even when tests were negative, or 2) there was increased use of presumptive antibiotic treatment for patients with negative RDTs. More systematic and large scale analyses are needed to determine the true impact of RDTs on correct ACT use but this preliminary evidence suggests an opportunity for developing more comprehensive diagnostics that can diagnose both malaria and other treatable causes of febrile illness. This test should include malaria diagnosis but also other common causes of febrile illness such as tuberculosis, pneumonia, or meningitis. Panel tests that can be used at the point of care in resource poor settings would better empower health workers to correctly treat not just malaria positive patients but also provide alternative treatments for malaria negative patients. Many diagnostics currently in development for malaria are focusing on finding novel means of detecting the parasites. One project in preclinical evaluation aims to use a high-resolution lens on a modified smartphone to detect parasites. Another, being developed by the Institute for Electrical and Electronics Engineers, hopes to use magnetic interactions to detect low levels of parasitemia without needing to take a blood sample. References 1. G6PD deficiency is the most common enzymopathy worldwide affecting more than 330 million people through more than 160 different mutations. This deficiency was first discovered after observation of hemolysis in malaria patients treated with primaquine, an 8-aminoquinoline. Nkhoma ET et al. (2009) “The global prevalence of glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis.” Blood Cells Mol Dis 42: 267–278. Get Involved To learn how you can get involved in neglected disease drug, vaccine or diagnostic research and development, or to provide updates, changes, or corrections to the Global Health Primer website, please view our FAQs or contact us at globalhealthprimer@bvgh.org. Tools Drugs | Vaccines | Diagnostics | Get Involved The following series of tables describe the availability of tools for research, discovery, and development of novel drugs, vaccines, and diagnostics for malaria. The tools listed in the following tables are not intended to be an all-inclusive list but rather capture the most common tools used for drug, vaccine, and diagnostic development. Drug Development Tools Basic Research: Target Identification Genome: Sequenced and annotated Key databases: Plasmodium Genomics Resource In vitro culture: Possible for P. falciparum but not P. vivax; mouse models often used for culture of pre-erythrocytic stages Target Validation Gene knock-outs: Yes (erythrocytic stages only) Conditional gene knock-outs: Two methods published, not yet widely applied Transposon mutagenesis: Possible RNAi: No, parasite missing key biological pathway components Other antisense technology: Yes Viability assays: Yes Transcription microarrays: Yes Proteomics: Yes Crystal structures: Not extensive, difficulty producing recombinant proteins Screening: Hit/Lead Identification Optimization Pre-clinical Validation Whole-cell screening assays: Yes, multiple assays for erythrocytic stages; assays in development for pre-erythrocytic Animal models: Yes; “humanized” mouse model available for P. falciparum; P. falciparum can also infect new world monkeys; P. berghei Monitoring treatment efficacy: Yes, microscopy is the gold standard, RDTs remain positive up to two weeks after treatment completion stages using mouse models most common mouse model used for drug discovery (also P. yoeli and P. chabaudi but less common) Availability of endpoints: Yes, clearance of parasitemia Enzymatic screening assays: Yes, but difficulty producing recombinant proteins, is sometimes limiting Clinical Validation Availability of surrogate endpoints: No Access to clinical trial patients/sites: Yes Back to Top Vaccine Development Tools Basic Research: Antigen Identification See drug development tools above Immune Response Characterization Clinical Validation Predictive animal models: No, although multiple mouse models available, little correlation with human response Surrogate markers of protection: No Detection of endogenous antigen specific response in clinical samples: Yes, not fully characterized Challenge studies possible: Yes Natural immunity well characterized: No, natural immunity minimal, transient, and not well understood Back to Top Diagnostic Development Tools Basic Research: Biomarker Identification See drug development tools above Biomarker Validation Biomarkers known: Yes Access to clinical samples: Yes, as part of RDT testing validated clinical sample registry being developed by TDR Clinical Validation Access to clinical trial patients/sites: Yes Treatment available if diagnosed: Yes Possible sample types: Blood Get Involved To learn how you can get involved in neglected disease drug, vaccine or diagnostic research and development, or to provide updates, changes, or corrections to the Global Health Primer website, please view our FAQs or contact us at globalhealthprimer@bvgh.org. Back to Top Product Details 2-0, 3-0 desulfated heparin (ODSH) Synonyms: 2-0, 3-0 desulfated heparin (ODSH) Heparin derivatives with low anticooaggulation Disease: Malaria Target/Technology: Anti-inflammatory Specific Indication: adjunct for severe disease Mechanism of Action: Product Type: Drug Molecule Class: Administration Route: PRV Elegible? No Notes: Clinical Trials: Publications: 4-aminoquinoline derivatives Synonyms: 4-aminoquinoline derivatives Chloroquine derivatives that overcome chloroquine resistance Disease: Malaria Target/Technology: Chloroquine-related Specific Indication: chloroquine resistant Mechanism of Action: Product Type: Drug Molecule Class: 4-aminoquinoline Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: 97/78 Synonyms: 97/78 Notes: Disease: Malaria Target/Technology: Artemisinin-related Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Synthetic derivative of artemisinin PRV Elegible? No Administration Route: Clinical Trials: Publications: 99/411 Synonyms: 99/411 Notes: Disease: Malaria Target/Technology: Artemisinin-related Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Artemisinin derivative PRV Elegible? Yes Administration Route: Clinical Trials: Publications: Acridones Synonyms: Acridones Notes: Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Acridones PRV Elegible? Yes Administration Route: Clinical Trials: Publications: AdCh63 AMA-1 Synonyms: AdCh63 AMA-1 Disease: Malaria Target/Technology: Viral vector vaccines Specific Indication: Preventive, P. falciparum erythrocytic stage Mechanism of Action: AMA-1 Product Type: Vaccine PRV Elegible? Yes Notes: Clinical Trials: NCT01142765 AdCh63 ME-TRAP Molecule Class: Simian adenovirus Administration Route: IM Publications: Synonyms: AdCh63 ME-TRAP Disease: Malaria Target/Technology: Viral vector vaccines Specific Indication: Preventive, P. falciparum pre-erythrocytic and erythrocytic stages Mechanism of Action: ME-TRAP, a chimeric Malaria antigen composed of the liver-stage TRAP antigen fused to a polyepitope string including T- and B-cell epitopes from different stages of the parasite life cycle Product Type: Vaccine PRV Elegible? Yes Molecule Class: Simian adenovirus Administration Route: IM Notes: Clinical Trials: This vaccine is being tested alone and with a boost of of MVA ME-TRAP. NCT01142765 NCT00890019 AdCh63 MSP-1 Synonyms: Disease: Target/Technology: AdCh63 MSP-1 Malaria Viral vector vaccines Specific Indication: Preventive, P. falciparum erythrocytic stage Mechanism of Action: MSP-1 Product Type: Vaccine PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Simian adenovirus Administration Route: IM Publications: NCT01142765 NCT01003314 AdVac Synonyms: Crucell Ad35.CS.01 AdVac AdVac Disease: Malaria Target/Technology: Viral vector vaccines Specific Indication: Preventive, P. falciparum pre-erythrocytic stage Mechanism of Action: CSP; Adenovirus Product Type: Vaccine PRV Elegible? Yes Molecule Class: Adenovirus Administration Route: IM Publications: Notes: Clinical Trials: Previously in prime-boost development with Ad26.CS.01. Entering phase II in prime-boost combination with RTS,S recombinant protein vaccine. NCT01018459 Publications: AMA1 Synonyms: AMA1 Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: AMA1-C1/Alhydrogel Synonyms: AMA1-C1/Alhydrogel Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Preventive, P. falciparum erythrocytic stage Mechanism of Action: Mixture of two recombinant synthetic AMA1 proteins from two Plasmodium falciparum strains Product Type: Vaccine PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Administration Route: IM Publications: NCT00984763 NCT00427167 NCT00344539 NCT00414336 NCT00740090 AMA1-DiCo Synonyms: AMA1-DiCo Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: PRV Elegible? Administration Route: Yes Clinical Trials: Notes: Publications: A diversity covering approach to increase immunogenicity to multiple AMA-1 alleles. For more information on this product, see European Vaccine Initiative. Aminopyridines Synonyms: Aminopyridines Notes: Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Aminopyridine PRV Elegible? Yes Administration Route: Clinical Trials: Publications: AN3661 Synonyms: AN3661 Oxaboroles Notes: Disease: Malaria Target/Technology: Boron Chemistry Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Oxaboroles PRV Elegible? Yes Administration Route: Clinical Trials: Publications: AnAPN-1 Synonyms: AnAPN-1 Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Transmission blocking Mechanism of Action: AnAPN-1 Product Type: Vaccine Molecule Class: PRV Elegible? Yes Administration Route: Notes: Clinical Trials: Publications: AQ-13 Synonyms: AQ-13 Notes: Disease: Malaria Target/Technology: Chloroquine-related Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: 4-aminoquinoline PRV Elegible? Yes Administration Route: Oral Clinical Trials: Publications: NCT00323375 NCT00455494 ARCO Synonyms: Naphthoquine-artemisinin ARCO Disease: Malaria Specific Indication: Product Type: Drug PRV Elegible? No Notes: Clinical Trials: Target/Technology: Combination: Artemisinin-related and Chloroquine-related Mechanism of Action: Molecule Class: Artemisinin and 4-aminoquinoline Administration Route: Publications: 19671190 19464245 Artemisone Synonyms: Artemisone Disease: Malaria Target/Technology: Artemisinin-related Specific Indication: artesunate resistant Mechanism of Action: Product Type: Drug PRV Elegible? Yes Molecule Class: Artemisinin derivative Administration Route: Oral Notes: Clinical Trials: Publications: NCT00936767 Arterolane + piperaquine Synonyms: Arterolane + piperaquine Rbx 11160 Disease: Malaria Specific Indication: Target/Technology: Combination: Artemisinin-related and Chloroquine-related Mechanism of Action: Combination Product Type: Drug Molecule Class: Combination: Synthetic endoperoxide + 4-aminoquinoline PRV Elegible? Yes Administration Route: Oral Notes: Clinical Trials: Publications: NCT00362050 ArTiMist Synonyms: artemether ArTiMist Disease: Malaria Target/Technology: Artemisinin-related Specific Indication: severe malaria Mechanism of Action: Product Type: Drug Administration Route: Sublingual PRV Elegible? No Notes: Molecule Class: Artemisinin derivative Clinical Trials: Publications: NCT01047436 AZCQ Synonyms: Azithromycin-chloroquine (AZCQ) Zithromax-chloroquine AZCQ Azithromycin-chloroquine (AZCQ) Disease: Malaria Specific Indication: IPTp Product Type: Drug PRV Elegible? No Target/Technology: Combination: Antibiotic and Chloroquine-related Mechanism of Action: Combination Molecule Class: Combination Administration Route: Oral Notes: Clinical Trials: Publications: NCT01103713 NCT01103063 BSAM-2/Alhydrogel Synonyms: BSAM-2/Alhydrogel Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Preventive, P. falciparum erythrocytic stage Mechanism of Action: MSP-1 and AMA-1 Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: NCT00889616 Cell based screening/lead identification Synonyms: Cell based screening/lead identification Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Administration Route: PRV Elegible? No Notes: Clinical Trials: Publications: Cell based screening/lead optimization Synonyms: Cell based screening/lead optimization Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: PRV Elegible? No Administration Route: Notes: Clinical Trials: Publications: CelTOS + GLA-SE Synonyms: Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Mechanism of Action: antigen + adjuvant Product Type: Vaccine PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Administration Route: Publications: CEM 101 Synonyms: CEM 101 Disease: Malaria Target/Technology: Unknown Specific Indication: P. vivax Mechanism of Action: Product Type: Drug Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: Centanamycin Synonyms: Centanamycin AS-1-145 Disease: Malaria Target/Technology: DNA damage Specific Indication: Mechanism of Action: induces DNA damage Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Indole Administration Route: Publications: 18275274 Chimigen malaria vaccine Synonyms: Chimigen malaria vaccine Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Preventive Mechanism of Action: CSP, AMA, LSA, and MSP Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: Combines four malaria antigens and targets dendritic cells. CSP Synonyms: CSP Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: CSP-EPA/Alhydrogel Synonyms: CSP-EPA/Alhydrogel Pre-erythrocytic malaria vaccines Disease: Malaria Target/Technology: Unknown Specific Indication: Preventive, P. falciparum pre-erythrocitic stage Mechanism of Action: Product Type: Vaccine Administration Route: Molecule Class: PRV Elegible? Yes Notes: CSVAC Clinical Trials: Publications: Synonyms: CSVAC Disease: Malaria Target/Technology: Viral vector vaccines Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Clinical Trials: Notes: Publications: This product aims to increase immunogenicity of a viral vector vaccine by using the circumsporozoite protein to inhibit p. falciparum infection. See European Vaccine Initiative. Dihydroorotate dehydrogenase (DHODH) inhibitors Synonyms: Dihydroorotate dehydrogenase (DHODH) inhibitors Disease: Malaria Target/Technology: Nucleic acid synthesis Specific Indication: Mechanism of Action: Nucleoside biosynthesis inhibitor/Dihydroorotate dehydrogenase (DHODH) inhibitor Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Administration Route: Publications: 21517059 DNA-Ad Synonyms: DNA-Ad Disease: Malaria Target/Technology: Combination: DNA and Viral vector Specific Indication: Preventive, P. falciparum pre-erythrocytic and erythrocytic stages Mechanism of Action: DNA prime (using virosomes) in combination with adenovirus boost Product Type: Vaccine Molecule Class: Adenovirus Administration Route: PRV Elegible? Yes Notes: Clinical Trials: NCT00870987 Publications: DPAP inhibitors Synonyms: DPAP inhibitors Disease: Malaria Target/Technology: Proteases Specific Indication: Mechanism of Action: Inhibition of malaria cathepsin C-like proteases Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Administration Route: Publications: 20797610 20700487 dUTPase inhibitors Synonyms: dUTPase inhibitors Disease: Malaria Target/Technology: Nucleic acid synthesis Specific Indication: Mechanism of Action: dUTPase inhibitors Product Type: Drug PRV Elegible? No Notes: Clinical Trials: Molecule Class: Administration Route: Publications: 21246738 16161998 EBA/Rh Synonyms: EBA/Rh Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: EBA-175 RII-NG Clinical Trials: Publications: Synonyms: EBA-175 RII-NG Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Preventive, P. falciparum erythrocytic stage Mechanism of Action: EBA Product Type: Vaccine Molecule Class: Administration Route: IM PRV Elegible? Yes Notes: Clinical Trials: Publications: NCT00347555 NCT01026246 16735084 20702657 EP1300 polyepitope DNA vaccine Synonyms: EP1300 polyepitope DNA vaccine Disease: Malaria Target/Technology: DNA vaccines Specific Indication: Preventive Mechanism of Action: Polyepitope Product Type: Vaccine Molecule Class: PRV Elegible? Yes Administration Route: IM Notes: Clinical Trials: DNA vaccine delivered using the TriGrid delivery system. NCT01169077 Falcpain 2/3 protease inhibitors Synonyms: Falcpain 2/3 protease inhibitors Disease: Malaria Target/Technology: Proteases Specific Indication: Mechanism of Action: Inhibition of falcipain 2/3 Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Administration Route: Publications: 16776649 Ferroquine + artesunate Publications: Synonyms: Ferroquine + artesunate SSR 97193 + artesunate Disease: Malaria Specific Indication: Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Target/Technology: Combination: Artemisinin-related and Chloroquine-related Mechanism of Action: Molecule Class: Combination: Artemisinin derivative + 4-aminoquinoline Administration Route: Oral Publications: NCT00988507 NCT00563914 FMP010 Synonyms: FMP010 Plasmodium falciparum Malaria protein 010 Notes: Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: MSP-1 PRV Elegible? Yes Administration Route: Clinical Trials: Publications: NCT00666380 NCT00317473 Fosclin Synonyms: Fosmidomycin + Clindamycin Fosclin Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: PRV Elegible? No Notes: Clinical Trials: NCT00217451 NCT00214643 NCT01002183 Administration Route: Oral Publications: Genz DHODH Synonyms: Genz DHODH Disease: Malaria Target/Technology: Nucleic acid synthesis Specific Indication: Mechanism of Action: Nucleoside biosynthesis inhibitor/Dihydroorotate dehydrogenase (DHODH) inhibitor Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Administration Route: Publications: Genz-668764 Synonyms: Genz-668764 Genz Aminoindole Notes: Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Aminoindoles PRV Elegible? Yes Administration Route: Clinical Trials: Publications: GMZ2 Synonyms: GMZ2 Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Preventive, P. falciparum erythrocytic stage Mechanism of Action: GLURP and MSP3 Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: GNF156 Clinical Trials: Publications: NCT00397449 NCT00424944 NCT00703066 20009515 Synonyms: GNF156 Notes: Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Imidazolopiperazines PRV Elegible? No Administration Route: Oral Clinical Trials: Publications: GSK 2243979A and GSK 2223413A Synonyms: GSK 2243979A and GSK 2223413A Backup program: 4-pyridone Disease: Malaria Target/Technology: Energy metabolism Specific Indication: Mechanism of Action: Inhibits electron transport chain in the mitochondrion Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: 4-pyridone Administration Route: Publications: GSK 932121 Synonyms: GSK 932121 4-pyridone class inhibitors Disease: Malaria Target/Technology: Energy metabolism Specific Indication: Mechanism of Action: Inhibits electron transport chain in the mitochondrion Product Type: Drug PRV Elegible? Yes Notes: Molecule Class: 4-pyridone Administration Route: Clinical Trials: Publications: NCT00811356 19596869 Hypoestoxide Synonyms: Hypoestoxide Disease: Malaria Target/Technology: Kinases Specific Indication: Mechanism of Action: Inhibition of IKB kinase Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Natural product Administration Route: Oral Publications: iBIO malaria vaccine research program Synonyms: iBIO malaria vaccine research program Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? No Notes: Clinical Trials: Publications: Identification of new diagnostic targets Synonyms: Disease: Malaria Technology: Immunoassay Specific Indication: Antigen detection Sample of Type: Blood Portability: Unknown Training Required: Unknown Notes: Clinical Trials: FIND is working with several partners to discover antigenic targets for point-of-care malaria diagnostics. Imidazolidinedione analogs Synonyms: Imidazolidinedione analogs Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Imidazolidinedione PRV Elegible? No Administration Route: Publications: Notes: Clinical Trials: Publications: IMX-MSP4 Synonyms: IMX-MSP4 Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: Industry screening efforts Synonyms: Industry screening efforts Notes: Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Multiple PRV Elegible? Yes Administration Route: Clinical Trials: Publications: ISPA-028 Synonyms: ISPA-028 Plasmodial surface anion channel (PSAC) inhibitor discovery Disease: Malaria Target/Technology: Ion channels Specific Indication: Drug resistant P. falciparum Mechanism of Action: Plasmodial surface anion channel (PSAC) inhibitor Product Type: Drug Molecule Class: Administration Route: PRV Elegible? No Notes: Clinical Trials: Publications: 21620134 20101003 JAIVAC-1 Synonyms: JAIVAC-1 Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Preventive, P. falciparum erythrocytic stage Mechanism of Action: rPfMSP-119 and rPfEBA175 Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: 20009515 LAMP Plasmodium assay Synonyms: Notes: Disease: Malaria Technology: Nucleic acid based Specific Indication: Antigen detection Sample of Type: Blood Portability: Peripheral laboratory Training Required: Unknown Clinical Trials: Publications: Lifelens Synonyms: Disease: Malaria Technology: Cell-based Specific Indication: Erythrocytic stage Sample of Type: Blood Portability: Handheld Training Required: Minimal Notes: Clinical Trials: This smartphone platform uses a high-resolution camera and special software to analyze blood sample for malaria-infected red blood cells. Magneto-optic Hemozoin detection Synonyms: Disease: Technology: Publications: Malaria Emerging Technology Specific Indication: low-level parasitemia detection Sample of Type: Other Portability: Table-top Training Required: Moderate Clinical Trials: Notes: This tests uses magneto-optic detection of hemozoin crystals through the capillary bed (observed as a change in magnetic transmittance) as a test for malaria. Malaria DNA vaccine Synonyms: Malaria DNA vaccine Disease: Malaria Target/Technology: DNA vaccines Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: Malaria drug discovery program Synonyms: Malaria drug discovery program Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: Malaria tSVP Synonyms: Malaria tSVP Synthetic Vaccine Particle vaccine Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: Publications: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: Methylene blue + amodiaqine or artesunate Synonyms: Methylene blue + amodiaqine or artesunate Notes: Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Combination PRV Elegible? No Administration Route: Oral Clinical Trials: Publications: NCT00545935 Microfluidic modeling Synonyms: Notes: Disease: Malaria Technology: Emerging Technology Specific Indication: Severe malaria pathogenesis modelling Sample of Type: Blood Portability: Advanced laboratory Training Required: Advanced Clinical Trials: Publications: 17658948 MK 4815 Synonyms: MK 4815 Disease: Malaria Target/Technology: Energy metabolism Specific Indication: Mechanism of Action: Inhibits electron transport chain in the mitochondrion Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Administration Route: Publications: MSP3-LSP Synonyms: MSP3-LSP Disease: Malaria Target/Technology: Peptide Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: An MSP3-LP3 vaccine uses long synthetic peptides of the merozoite surface protein 3 conserved region to induce immunity against p. falciparum. NCT01341704 16299295 MVA AMA-1 Synonyms: MVA AMA-1 Disease: Malaria Target/Technology: Viral vector vaccines Specific Indication: Preventive, P. falciparum erythrocytic stage Mechanism of Action: AMA-1 Product Type: Vaccine PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: MVA Administration Route: IM Publications: NCT01142765 MVA ME-TRAP Synonyms: MVA ME-TRAP Disease: Malaria Target/Technology: Viral vector vaccines Specific Indication: Preventive, P. falciparum pre-erythrocytic and erythrocytic stages Mechanism of Action: ME-TRAP, a chimeric Malaria antigen composed of the liver-stage TRAP antigen fused to a polyepitope string including T- and B-cell epitopes from different stages of the parasite life cycle Product Type: Vaccine PRV Elegible? Yes Molecule Class: MVA Administration Route: IM Notes: Clinical Trials: Publications: NCT01142765 NCT00890019 MVA MSP-1 Synonyms: MVA MSP-1 Disease: Malaria Target/Technology: Viral vector vaccines Specific Indication: Preventive, P. falciparum erythrocytic stage Mechanism of Action: MSP-1 Product Type: Vaccine PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: MVA Administration Route: IM Publications: NCT01142765 NCT01003314 ND-901 Synonyms: ND-901 Notes: Disease: Malaria Target/Technology: Chloroquine-related Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: 4-aminoquinoline PRV Elegible? Yes Administration Route: Oral Clinical Trials: Publications: NIH/Cytos malaria vaccine research program Synonyms: NIH/Cytos malaria vaccine research program Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: PRV Elegible? Yes Administration Route: Notes: Clinical Trials: Publications: NITD 609 Synonyms: NITD 609 Notes: Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Spiroindolone PRV Elegible? Yes Administration Route: Clinical Trials: Publications: 20813948 NMRC-M3V-Ad-PfCA Synonyms: NMRC-M3V-Ad-PfCA Disease: Malaria Target/Technology: Viral vector vaccines Specific Indication: Preventive, P. falciparum pre-erythrocytic and erythrocytic stages Mechanism of Action: PfCSP and PfAMA1 Product Type: Vaccine Molecule Class: Adenovirus Administration Route: IM PRV Elegible? Yes Notes: Clinical Trials: Publications: NCT00392015 Novartis series lead optimization Synonyms: Novartis series lead optimization Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: imidazolopyrazines; pyrrolidines; imidazolopiperazines Product Type: Drug PRV Elegible? Yes Molecule Class: Multiple Administration Route: Notes: Clinical Trials: Publications: NPC1161B Synonyms: NPC1161B 8-aminoquinoline derivatives Notes: Disease: Malaria Target/Technology: Primaquine-related Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: 8-aminoquinoline PRV Elegible? No Administration Route: Clinical Trials: Publications: 17075340 N-tert butyl isoquine Synonyms: N-tert butyl isoquine GSK369796 4-aminoquinoline derivatives Notes: Disease: Malaria Target/Technology: Chloroquine-related Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: 4-aminoquinoline PRV Elegible? No Administration Route: Clinical Trials: Publications: NCT00675064 19222165 OZ 439 Synonyms: OZ 439 Notes: Disease: Malaria Target/Technology: Artemisinin-related Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Synthetic endoperoxidase PRV Elegible? Yes Administration Route: Oral Clinical Trials: NCT01213966 NCT00928083 Publications: P218 Synonyms: P218 Dihydrofolate reductase inhibitors Disease: Malaria Target/Technology: Nucleic acid synthesis Specific Indication: Mechanism of Action: Nucleoside biosynthesis inhibitor/DHFR inhibitor Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Molecule Class: Administration Route: Publications: P27A Synonyms: P27A Disease: Malaria Target/Technology: Peptide Specific Indication: Mechanism of Action: Preventive, P. falciparum erythrocytic stage Fragment P27A of the novel malaria protein PFF0165c Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: 20009515 p52-/p36- GAP Vaccine Synonyms: p52-/p36- GAP Vaccine GAP vaccines Disease: Malaria Target/Technology: Live attenuated vaccines Specific Indication: Preventive, P. falciparum Mechanism of Action: Genetically attenuated live parasites invade liver cells but cannot replicate Product Type: Vaccine PRV Elegible? Yes Notes: Clinical Trials: NCT01024686 Molecule Class: Administration Route: Mosquito bite Publications: PA1103/SAR116242 Synonyms: PA1103/SAR116242 Notes: Disease: Malaria Target/Technology: Artemisinin-related Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Synthetic endoperoxidase PRV Elegible? Yes Administration Route: Clinical Trials: Publications: pDNA malaria vaccine Synonyms: pDNA malaria vaccine Disease: Malaria Target/Technology: DNA vaccines Specific Indication: Preventive, P. falciparum Mechanism of Action: pre-erythrocytic stage Molecule Class: Product Type: Vaccine Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: PE selection Synonyms: PE selection Disease: Malaria Target/Technology: Unknown Specific Indication: pre-erythrocytic Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: PEV301 & 302 Synonyms: Disease: Target/Technology: PEV301 & 302 Malaria Recombinant/purified protein vaccines Specific Indication: Preventive, P. falciparum pre-erythrocytic and erythrocytic stages Mechanism of Action: AMA-1 and CSP delivered in virosomes Product Type: Vaccine Administration Route: Molecule Class: PRV Elegible? Yes Notes: Clinical Trials: Publications: Previously evaluated as PEV3A. NCT00513669 NCT00408668 18231580 Pfs25-EPA/Alhydrogel, Pfs230, Pfs25-Pfs25/Alhydrogel Synonyms: Pfs25-EPA/Alhydrogel, Pfs230, Pfs25-Pfs25/Alhydrogel Transmission blocking vaccines Disease: Malaria Target/Technology: Unknown Specific Indication: Transmission blocking, P. falciparum Mechanism of Action: Product Type: Vaccine Administration Route: Molecule Class: PRV Elegible? Yes Notes: Clinical Trials: Publications: Pfs48 Synonyms: Pfs48 Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Transmission blocking Mechanism of Action: CH-rPfs48/45 Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: 19623257 PfSPZ Synonyms: PfSPZ Disease: Malaria Target/Technology: Live attenuated vaccines Specific Indication: Preventive, P. falciparum pre-erythrocytic stage Mechanism of Action: Irradiated sporozoites invade liver cells but cannot replicate Product Type: Vaccine Molecule Class: PRV Elegible? Yes Administration Route: SC Notes: Clinical Trials: Preliminary results from ongoing Phase I/II trial are not promising, and the program is facing funding shortages. It is unclear at this point if this program will continue. NCT01086917 NCT01001650 PlasProtecT Synonyms: PlasProtecT Disease: Malaria Target/Technology: Live attenuated vaccines Specific Indication: Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: PMX-30024 and PMX-70008 Synonyms: PMX-30024 and PMX-70008 Disease: Malaria Target/Technology: Membrane disruption Specific Indication: Mechanism of Action: defensin mimetic antibiotic Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: Pregnancy malaria vaccines Molecule Class: Administration Route: Publications: Publications: Synonyms: Pregnancy malaria vaccines Disease: Malaria Target/Technology: Unknown Specific Indication: Preventive, P. falciparum in pregnancy Mechanism of Action: Product Type: Vaccine Administration Route: Molecule Class: PRV Elegible? Yes Notes: Clinical Trials: Publications: PvCSP/AS01 Synonyms: PvCSP/AS01 VMP001/AS01B Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Mechanism of Action: Preventive, P. vivax pre-erythrocytic stage Molecule Class: Product Type: Vaccine Administration Route: IM PRV Elegible? Yes Notes: Clinical Trials: Publications: NCT01157897 PvDBII Synonyms: PvDBII P. vivax duffy binding protein II Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: P.vivax Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: PvRII Clinical Trials: Publications: Synonyms: PvRII Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Preventive, P. vivax erythrocytic stage Mechanism of Action: DBP Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: Pyrazoles Synonyms: Pyrazoles Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: Quinoline Methanol Synonyms: Quinoline Methanol Notes: Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Mefloquine derivative PRV Elegible? Yes Administration Route: Clinical Trials: Publications: Quinolones Synonyms: Quinolones Disease: Malaria Target/Technology: Nucleic acid synthesis Specific Indication: Mechanism of Action: Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: DNA gyrase inhibitor Molecule Class: Quinolones Administration Route: Publications: Restanza Synonyms: Cethromycin Restanza Disease: Malaria Target/Technology: Antibiotic Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: PRV Elegible? Yes Administration Route: Oral Clinical Trials: Notes: Restanza was originally developed by Advanced Life Sciences for community acquired pneumonia, but is also in testing for efficacy against anthrax, tularemia, plague, and malaria. RKA 182 Synonyms: RKA 182 Notes: Disease: Malaria Target/Technology: Artemisinin-related Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Synthetic endoperoxidase PRV Elegible? No Administration Route: Clinical Trials: Publications: 20629058 RNAi therapeutic Synonyms: RNAi therapeutic Disease: Malaria Target/Technology: RNAi therapeutic Specific Indication: Mechanism of Action: Host-targeted RNAi Product Type: Publications: Drug PRV Elegible? No Notes: Clinical Trials: Molecule Class: RNA Administration Route: Publications: RTS,S/AS01 Synonyms: RTS,S/AS01 Mosquirix GSK malaria vaccine 257049 Disease: Malaria Target/Technology: Recombinant/purified protein vaccines Specific Indication: Preventive, P. falciparum pre-erythrocytic stage Mechanism of Action: PfCSP protein fused to HBsAG (S) antigen that can self assemble into viral particles Product Type: Vaccine Molecule Class: PRV Elegible? Yes Administration Route: IM Notes: Clinical Trials: Publications: In phase III alone and phase II in prime-boost combination with Ad35.CS.01. NCT00866619 NCT00436007 NCT01148459 NCT00197028 NCT01366534 NCT01231503 NCT01345240 NCT00323622 NCT00443131 NCT01323972 NCT00289185 NCT00307021 NCT00360230 NCT00380393 20553771 21443960 SAR 97276 Synonyms: SAR 97276 Disease: Malaria Target/Technology: Unknown Specific Indication: adjunct for severe disease Mechanism of Action: Product Type: Drug PRV Elegible? No Molecule Class: bis-thiazolium Administration Route: Notes: Clinical Trials: Publications: NCT00739206 Sevuparin Synonyms: Sevuparin DF02 Heparin derivatives with low anticooaggulation Disease: Malaria Target/Technology: Anti-inflammatory Specific Indication: adjunct for severe disease Mechanism of Action: Product Type: Drug Molecule Class: Administration Route: PRV Elegible? No Notes: Clinical Trials: Publications: SSJ-183 Synonyms: SSJ-183 Disease: Malaria Target/Technology: Unknown Specific Indication: Mechanism of Action: Product Type: Drug Molecule Class: Administration Route: PRV Elegible? Yes Notes: Clinical Trials: Publications: Tafenoquine Synonyms: Tafenoquine SB-252263 Disease: Malaria Target/Technology: Primaquine-related Specific Indication: P. vivax Mechanism of Action: Product Type: Drug PRV Elegible? Yes Notes: Clinical Trials: NCT00871156 Molecule Class: 8-aminoquinoline Administration Route: Oral Publications: NCT01205178 Tinidazole Synonyms: Tinidazole Disease: Malaria Target/Technology: Unknown Specific Indication: P. vivax Mechanism of Action: Product Type: Drug Molecule Class: Administration Route: Oral PRV Elegible? No Notes: Clinical Trials: Publications: NCT00811096 Toxoplasma KO Vaccine Synonyms: Toxoplasma KO Vaccine Disease: Malaria Target/Technology: Parasite vector Specific Indication: Preventive Mechanism of Action: Product Type: Vaccine Molecule Class: Administration Route: PRV Elegible? No Notes: Clinical Trials: Publications: Live attenuated Toxoplasma gondii strain used as vector to express malaria antigens. Developer Details GlaxoSmithKline (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria GSK 932121 Phase I GlaxoSmithKline (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria RTS,S/AS01 Phase III GlaxoSmithKline (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria PvCSP/AS01 Phase II GlaxoSmithKline (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria AdVac Phase II GlaxoSmithKline (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria N-tert butyl isoquine Phase I GlaxoSmithKline (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria Tafenoquine Phase I GlaxoSmithKline (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria GSK 2243979A and GSK 2223413A Discovery GlaxoSmithKline (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria FMP010 Phase I Liverpool School of Tropical Medicine (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria N-tert butyl isoquine Phase I University of Mississippi (United States) Type Disease Product/Research Program Current Phase Drug Malaria NPC1161B Pre-clinical University of Liverpool (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria RKA 182 Pre-clinical Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Novartis series lead optimization Discovery Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Aminopyridines Discovery Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Pyrazoles Discovery Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Quinolones Discovery Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Quinoline Methanol Discovery Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Genz DHODH Discovery Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria GNF156 Pre-clinical Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria AZCQ Phase III Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Artemisone Phase II Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Tafenoquine Phase I Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria NITD 609 Phase I Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria MK 4815 Pre-clinical Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria CEM 101 Pre-clinical Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria P218 Pre-clinical Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria GSK 2243979A and GSK 2223413A Discovery Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Dihydroorotate dehydrogenase (DHODH) inhibitors Discovery Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Genz-668764 Discovery Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria AN3661 Pre-clinical Medicines for Malaria Venture (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria OZ 439 Phase II Genomics Institute of the Novartis Research Foundation (United States) Type Disease Product/Research Program Current Phase Drug Malaria GNF156 Pre-clinical Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Drug Malaria Acridones Discovery Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Drug Malaria Quinoline Methanol Discovery Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria NMRC-M3V-Ad-PfCA Phase II Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PvCSP/AS01 Phase II Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria p52-/p36- GAP Vaccine Phase II Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Drug Malaria Imidazolidinedione analogs Discovery Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Drug Malaria Tafenoquine Phase I Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Drug Malaria Tinidazole Phase II Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria CelTOS + GLA-SE Pre-clinical Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Drug Malaria Restanza Pre-clinical Walter Reed Army Institute of Research (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria AMA1 Discovery Special Programme for Research and Training in Tropical Diseases (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Cell based screening/lead optimization Discovery Pfizer Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria Industry screening efforts Discovery Pfizer Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria Cell based screening/lead optimization Discovery Pfizer Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria AZCQ Phase III University of California, Berkeley (United States) Type Disease Product/Research Program Current Phase Drug Malaria DPAP inhibitors Discovery Stanford University (United States) Type Disease Product/Research Program Current Phase Drug Malaria DPAP inhibitors Discovery Central Drug Research Institute (India) Type Disease Product/Research Program Current Phase Drug Malaria 99/411 Pre-clinical Central Drug Research Institute (India) Type Disease Product/Research Program Current Phase Drug Malaria 97/78 Phase I Ipca Laboratories Ltd (India) Type Disease Product/Research Program Current Phase Drug Malaria 99/411 Pre-clinical Ipca Laboratories Ltd (India) Type Disease Product/Research Program Current Phase Drug Malaria 97/78 Phase I Merck & Co., Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria MK 4815 Pre-clinical Merck & Co., Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria Cell based screening/lead identification Discovery Chinese Academy of Military Medical Sciences (China) Type Disease Product/Research Program Current Phase Drug Malaria ARCO Phase II Medivir (Sweden) Type Disease Product/Research Program Current Phase Drug Malaria dUTPase inhibitors Discovery Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria RTS,S/AS01 Phase III Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PfSPZ Phase II Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PvCSP/AS01 Phase II Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria AdVac Phase II Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PvRII Pre-clinical Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria pDNA malaria vaccine Pre-clinical Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria AnAPN-1 Pre-clinical Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria Pfs48 Discovery Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria CSP Discovery Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria AMA1 Discovery Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria EBA/Rh Discovery Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PvDBII Discovery Malaria Vaccine Initiative (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PE selection Discovery Naval Medical Research Center (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria NMRC-M3V-Ad-PfCA Phase II Naval Medical Research Center (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PfSPZ Phase II Naval Medical Research Center (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria DNA-Ad Phase II Naval Medical Research Center (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PE selection Discovery University of Maryland Center for Vaccine Development (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PfSPZ Phase II Sanaria, Inc. (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PfSPZ Phase II Okairos Srl (Italy) Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 MSP-1 Phase II Okairos Srl (Italy) Type Disease Product/Research Program Current Phase Vaccine Malaria MVA MSP-1 Phase II Okairos Srl (Italy) Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 AMA-1 Phase II Okairos Srl (Italy) Type Disease Product/Research Program Current Phase Vaccine Malaria MVA AMA-1 Phase II Okairos Srl (Italy) Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 ME-TRAP Phase II Okairos Srl (Italy) Type Disease Product/Research Program Current Phase Vaccine Malaria MVA ME-TRAP Phase II The Jenner Institute (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 MSP-1 Phase II The Jenner Institute (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria MVA MSP-1 Phase II The Jenner Institute (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 AMA-1 Phase II The Jenner Institute (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria MVA AMA-1 Phase II The Jenner Institute (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 ME-TRAP Phase II The Jenner Institute (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria MVA ME-TRAP Phase II University of Oxford (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 MSP-1 Phase II University of Oxford (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria MVA MSP-1 Phase II University of Oxford (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 AMA-1 Phase II University of Oxford (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria MVA AMA-1 Phase II University of Oxford (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 ME-TRAP Phase II University of Oxford (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria MVA ME-TRAP Phase II University of Oxford (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria AMA1-C1/Alhydrogel Phase II University of Oxford (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria Artemisone Phase II University of Oxford (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria CSVAC Discovery University of Oxford (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria IMX-MSP4 Pre-clinical Imaxio (France) Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 MSP-1 Phase II Type Disease Product/Research Program Current Phase Vaccine Malaria MVA MSP-1 Phase II Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 AMA-1 Phase II Type Disease Product/Research Program Current Phase Vaccine Malaria MVA AMA-1 Phase II Type Disease Product/Research Program Current Phase Vaccine Malaria AdCh63 ME-TRAP Phase II Imaxio (France) Imaxio (France) Imaxio (France) Imaxio (France) Imaxio (France) Type Disease Product/Research Program Current Phase Vaccine Malaria MVA ME-TRAP Phase II Imaxio (France) Type Disease Product/Research Program Current Phase Vaccine Malaria IMX-MSP4 Pre-clinical Vical, Inc. (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria DNA-Ad Phase II National Institute of Allergy and Infectious Diseases (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria AMA1-C1/Alhydrogel Phase II National Institute of Allergy and Infectious Diseases (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria BSAM-2/Alhydrogel Phase I National Institute of Allergy and Infectious Diseases (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria EP1300 polyepitope DNA vaccine Phase I National Institute of Allergy and Infectious Diseases (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria EBA-175 RII-NG Phase I National Institute of Allergy and Infectious Diseases (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria Pfs25-EPA/Alhydrogel, Pfs230, Pfs25-Pfs25/Alhydrogel Discovery National Institute of Allergy and Infectious Diseases (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria CSP-EPA/Alhydrogel Discovery National Institute of Allergy and Infectious Diseases (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria Pregnancy malaria vaccines Discovery National Institute of Allergy and Infectious Diseases (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria Malaria tSVP Discovery National Institute of Allergy and Infectious Diseases (United States) Type Disease Product/Research Program Current Phase Drug Malaria ISPA-028 Discovery Seattle Biomedical Research Institute (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria p52-/p36- GAP Vaccine Phase II Seattle Biomedical Research Institute (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria PE selection Discovery Crucell (Netherlands) Type Disease Product/Research Program Current Phase Vaccine Malaria AdVac Phase II USAID Malaria Vaccine Development Program (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria AdVac Phase II Mymetics S.A. (Switzerland) Type Disease Product/Research Program Current Phase Vaccine Malaria PEV301 & 302 Phase I Swiss Tropical and Public Health Institute (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Novartis series lead optimization Discovery Swiss Tropical and Public Health Institute (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria SSJ-183 Discovery Swiss Tropical and Public Health Institute (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Aminopyridines Discovery Swiss Tropical and Public Health Institute (Switzerland) Type Disease Product/Research Program Current Phase Vaccine Malaria PEV301 & 302 Phase I Swiss Tropical and Public Health Institute (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria OZ 439 Phase II Pevion Biotech Ltd. (Switzerland) Type Disease Product/Research Program Current Phase Vaccine Malaria PEV301 & 302 Phase I VaxOnco (Korea (South)) Type Disease Product/Research Program Current Phase Vaccine Malaria EP1300 polyepitope DNA vaccine Phase I Ichor Medical Systems, Inc. (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria EP1300 polyepitope DNA vaccine Phase I Baylor College of Medicine (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria EBA-175 RII-NG Phase I Vakzine Projekt Management GmbH (Germany) Type Disease Product/Research Program Current Phase Vaccine Malaria GMZ2 Phase II Statens Serum Institut (Denmark) Type Disease Product/Research Program Current Phase Vaccine Malaria GMZ2 Phase II African Malaria Network Trust (Tanzania) Type Disease Product/Research Program Current Phase Vaccine Malaria MSP3-LSP Phase II African Malaria Network Trust (Tanzania) Type Disease Product/Research Program Current Phase Vaccine Malaria GMZ2 Phase II International Centre for Genetic Engineering and Biotechnology (Italy) Type Disease Product/Research Program Current Phase Vaccine Malaria JAIVAC-1 Phase I International Centre for Genetic Engineering and Biotechnology (Italy) Type Disease Product/Research Program Current Phase Vaccine Malaria PvRII Pre-clinical International Centre for Genetic Engineering and Biotechnology (Italy) Type Disease Product/Research Program Current Phase Vaccine Malaria PvDBII Discovery Sabin Vaccine Institute (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria AnAPN-1 Pre-clinical Johns Hopkins University Medical School (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria AnAPN-1 Pre-clinical Tulane University (United States) Type Disease Product/Research Program Current Phase Drug Malaria AQ-13 Phase I Tulane University (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria Pfs48 Discovery Gennova Biopharmaceuticals (India) Type Disease Product/Research Program Current Phase Vaccine Malaria CSP Discovery Gennova Biopharmaceuticals (India) Type Disease Product/Research Program Current Phase Vaccine Malaria EBA/Rh Discovery Gennova Biopharmaceuticals (India) Type Disease Product/Research Program Current Phase Vaccine Malaria Pfs48 Discovery Bharat Biotech (India) Type Disease Product/Research Program Current Phase Vaccine Malaria JAIVAC-1 Phase I European Vaccine Initiative (Germany) Type Disease Product/Research Program Current Phase Vaccine Malaria JAIVAC-1 Phase I European Vaccine Initiative (Germany) Type Disease Product/Research Program Current Phase Vaccine Malaria P27A Pre-clinical European Vaccine Initiative (Germany) Type Disease Product/Research Program Current Phase Vaccine Malaria GMZ2 Phase II European Vaccine Initiative (Germany) Type Disease Product/Research Program Current Phase Vaccine Malaria AMA1-DiCo Pre-clinical European Vaccine Initiative (Germany) Type Disease Product/Research Program Current Phase Vaccine Malaria CSVAC Discovery European Vaccine Initiative (Germany) Type Disease Product/Research Program Current Phase Vaccine Malaria MSP3-LSP Phase II Universite de Lausanne (Switzerland) Type Disease Product/Research Program Current Phase Vaccine Malaria P27A Pre-clinical ALMAC Group (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria P27A Pre-clinical London School of Hygiene and Tropical Medicine (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria AZCQ Phase III London School of Hygiene and Tropical Medicine (United Kingdom) Type Disease Product/Research Program Current Phase Vaccine Malaria MSP3-LSP Phase II Ranbaxy Laboratories Ltd. (India) Type Disease Product/Research Program Current Phase Drug Malaria Arterolane + piperaquine Phase III Hong Kong University of Science and Techology (China) Type Disease Product/Research Program Current Phase Drug Malaria Artemisone Phase II University of Nebraska (United States) Type Disease Product/Research Program Current Phase Drug Malaria OZ 439 Phase II Monash University (Australia) Type Disease Product/Research Program Current Phase Drug Malaria OZ 439 Phase II Monash University (Australia) Type Disease Product/Research Program Current Phase Drug Malaria Dihydroorotate dehydrogenase (DHODH) inhibitors Discovery Sanofi-Aventis (France) Type Disease Product/Research Program Current Phase Drug Malaria Industry screening efforts Discovery Sanofi-Aventis (France) Type Disease Product/Research Program Current Phase Drug Malaria SAR 97276 Phase II Sanofi-Aventis (France) Type Disease Product/Research Program Current Phase Drug Malaria Ferroquine + artesunate Phase II Sanofi-Aventis (France) Type Disease Product/Research Program Current Phase Drug Malaria PA1103/SAR116242 Pre-clinical Sanofi-Aventis (France) Type Disease Product/Research Program Current Phase Drug Malaria ASAQ Approved Heidelberg University (Germany) Type Disease Product/Research Program Current Phase Drug Malaria Methylene blue + amodiaqine or artesunate Phase II HC Berlin Pharma AG (Germany) Type Disease Product/Research Program Current Phase Drug Malaria ArTiMist Phase II Eastland Medical Systems Ltd (Australia) Type Disease Product/Research Program Current Phase Drug Malaria ArTiMist Phase II ProtoPharma Limited (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria ArTiMist Phase II Jomaa Pharma (Germany) Type Disease Product/Research Program Current Phase Drug Malaria Fosclin Phase II Immtech Pharmaceuticals Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria AQ-13 Phase I Novartis Institute for Tropical Diseases (Singapore) Type Disease Product/Research Program Current Phase Drug Malaria Novartis series lead optimization Discovery Novartis Institute for Tropical Diseases (Singapore) Type Disease Product/Research Program Current Phase Drug Malaria NITD 609 Phase I Cempra Pharmaceuticals (United States) Type Disease Product/Research Program Current Phase Drug Malaria CEM 101 Pre-clinical Portland State University (United States) Type Disease Product/Research Program Current Phase Drug Malaria Acridones Discovery Portland State University (United States) Type Disease Product/Research Program Current Phase Drug Malaria 4-aminoquinoline derivatives Pre-clinical DesignMedix (United States) Type Disease Product/Research Program Current Phase Drug Malaria Acridones Discovery DesignMedix (United States) Type Disease Product/Research Program Current Phase Drug Malaria 4-aminoquinoline derivatives Pre-clinical NeED Pharma (Italy) Type Disease Product/Research Program Current Phase Drug Malaria ND-901 Pre-clinical Palumed (France) Type Disease Product/Research Program Current Phase Drug Malaria PA1103/SAR116242 Pre-clinical PolyMedix Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria PMX-30024 and PMX-70008 Pre-clinical Spirogen Ltd. (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria Centanamycin Pre-clinical McGill University (Canada) Type Disease Product/Research Program Current Phase Drug Malaria Centanamycin Pre-clinical Novartis AG (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Novartis series lead optimization Discovery Novartis AG (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Industry screening efforts Discovery Novartis AG (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria Coartem Approved Biomedical Primate Research Centre (Netherlands) Type Disease Product/Research Program Current Phase Drug Malaria Novartis series lead optimization Discovery Biomedical Primate Research Centre (Netherlands) Type Disease Product/Research Program Current Phase Vaccine Malaria AMA1-DiCo Pre-clinical UT Southwestern Medical Center (United States) Type Disease Product/Research Program Current Phase Drug Malaria Dihydroorotate dehydrogenase (DHODH) inhibitors Discovery University of Washington (United States) Type Disease Product/Research Program Current Phase Drug Malaria Pyrazoles Discovery University of Washington (United States) Type Disease Product/Research Program Current Phase Drug Malaria Dihydroorotate dehydrogenase (DHODH) inhibitors Discovery University of Washington (United States) Type Disease Product/Research Program Current Phase Diagnostic Malaria Microfluidic modeling Pre-clinical Broad Institute of MIT and Harvard (United States) Type Disease Product/Research Program Current Phase Drug Malaria Industry screening efforts Discovery Broad Institute of MIT and Harvard (United States) Type Disease Product/Research Program Current Phase Drug Malaria Genz DHODH Discovery Broad Institute of MIT and Harvard (United States) Type Disease Product/Research Program Current Phase Drug Malaria Genz-668764 Discovery Genzyme (United States) Type Disease Product/Research Program Current Phase Drug Malaria Industry screening efforts Discovery Genzyme (United States) Type Disease Product/Research Program Current Phase Drug Malaria Genz DHODH Discovery Genzyme (United States) Type Disease Product/Research Program Current Phase Drug Malaria Genz-668764 Discovery University of California, San Francisco (United States) Type Disease Product/Research Program Current Phase Drug Malaria AN3661 Pre-clinical Anacor Pharmaceuticals, Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria AN3661 Pre-clinical Synstar Japan Co., Ltd. (Japan) Type Disease Product/Research Program Current Phase Drug Malaria SSJ-183 Discovery Centre for Drug Candidate Optimisation (Australia) Type Disease Product/Research Program Current Phase Drug Malaria SSJ-183 Discovery Centre for Drug Candidate Optimisation (Australia) Type Disease Product/Research Program Current Phase Drug Malaria Aminopyridines Discovery Centre for Drug Candidate Optimisation (Australia) Type Disease Product/Research Program Current Phase Drug Malaria Quinolones Discovery University of Cape Town (South Africa) Type Disease Product/Research Program Current Phase Drug Malaria Aminopyridines Discovery Drexel University College of Medicine (United States) Type Disease Product/Research Program Current Phase Drug Malaria Pyrazoles Discovery Drexel University College of Medicine (United States) Type Disease Product/Research Program Current Phase Drug Malaria Quinolones Discovery University of South Florida (United States) Type Disease Product/Research Program Current Phase Drug Malaria Quinolones Discovery Oregon Health & Science University (United States) Type Disease Product/Research Program Current Phase Drug Malaria Quinolones Discovery AstraZeneca (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria Industry screening efforts Discovery Cenix BioScience (Germany) Type Disease Product/Research Program Current Phase Drug Malaria RNAi therapeutic Discovery Alnylam Pharmaceuticals, Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria RNAi therapeutic Discovery ParaQuest, Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria Hypoestoxide Discovery Amura Therapeutics Ltd. (United Kingdom) Type Disease Product/Research Program Current Phase Drug Malaria Falcpain 2/3 protease inhibitors Discovery Dilafor (Sweden) Type Disease Product/Research Program Current Phase Drug Malaria Sevuparin Phase I ParinGenix, Inc. (United States) Type Disease Product/Research Program Current Phase Drug Malaria 2-0, 3-0 desulfated heparin (ODSH) Pre-clinical Eisai Inc. (Japan) Type Disease Product/Research Program Current Phase Drug Malaria Malaria drug discovery program Discovery Queensland Institute for Medical Research Type Disease Product/Research Program Current Phase Diagnostic Malaria Identification of new diagnostic targets Pre-clinical Foundation for Innovative New Diagnostics (Switzerland) Type Disease Product/Research Program Current Phase Diagnostic Malaria Identification of new diagnostic targets Pre-clinical Foundation for Innovative New Diagnostics (Switzerland) Type Disease Product/Research Program Current Phase Diagnostic Malaria LAMP Plasmodium assay Pre-clinical Royal Tropical Institute (Netherlands) Type Disease Product/Research Program Current Phase Diagnostic Malaria Identification of new diagnostic targets Pre-clinical Eiken Chemical (Japan) Type Disease Product/Research Program Current Phase Diagnostic Malaria LAMP Plasmodium assay Pre-clinical Hospital for Tropical Diseases (Vietnam) Type Disease Product/Research Program Current Phase Diagnostic Malaria LAMP Plasmodium assay Pre-clinical University of California, Davis Type Disease Product/Research Program Current Phase Diagnostic Malaria Lifelens Clinical Institute for Electrical and Electronics Engineers Type Disease Product/Research Program Current Phase Diagnostic Malaria Magneto-optic Hemozoin detection Pre-clinical Science Applications International Corporation (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria Malaria tSVP Discovery Selecta Biosciences (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria Malaria tSVP Discovery US Agency for International Development (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria CelTOS + GLA-SE Pre-clinical US Agency for International Development (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria FMP010 Phase I Infectious Disease Research Institute (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria CelTOS + GLA-SE Pre-clinical Bill & Melinda Gates Foundation (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria CelTOS + GLA-SE Pre-clinical Royal College of Surgeons in Ireland (Ireland) Type Disease Product/Research Program Current Phase Vaccine Malaria CSVAC Discovery Advanced Life Sciences (United States) Type Disease Product/Research Program Current Phase Drug Malaria Restanza Pre-clinical Avanti Therapeutics (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria Malaria DNA vaccine Pre-clinical National Institutes of Health (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria NIH/Cytos malaria vaccine research program Pre-clinical Cytos Biotechnology (Switzerland) Type Disease Product/Research Program Current Phase Vaccine Malaria NIH/Cytos malaria vaccine research program Pre-clinical iBIO (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria iBIO malaria vaccine research program Pre-clinical US Army Medical Research and Materiel Command (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria FMP010 Phase I Drugs for Neglected Diseases Initiative (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria ASAQ Approved Drugs for Neglected Diseases Initiative (Switzerland) Type Disease Product/Research Program Current Phase Drug Malaria ASMQ Approved Oswaldo Cruz Foundation (Brazil) Type Disease Product/Research Program Current Phase Drug Malaria ASMQ Approved Type Disease Product/Research Program Current Phase Drug Malaria ASMQ Approved Cipla (India) Griffith University (Australia) Type Disease Product/Research Program Current Phase Vaccine Malaria PlasProtecT Pre-clinical Inovio Pharmaceuticals, Inc. (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria pDNA malaria vaccine Pre-clinical University of Pennsylvania (United States) Type Disease Product/Research Program Current Phase Vaccine Malaria pDNA malaria vaccine Pre-clinical Paladin Biosciences division of Paladin Labs Inc. (Canada) Type Disease Product/Research Program Current Phase Vaccine Malaria Chimigen malaria vaccine Discovery VitamFero (France) Type Disease Product/Research Program Current Phase Vaccine Malaria Toxoplasma KO Vaccine Discovery Walter and Elizabeth Hall Institute of Medical Research (Australia) Type Disease Product/Research Program Current Phase Vaccine Malaria AMA1 Discovery Walter and Elizabeth Hall Institute of Medical Research (Australia) Type Disease Product/Research Program Current Phase Vaccine Malaria EBA/Rh Discovery
