In an exclusive interview with NewsGhana, the scientist behind one of the most significant antimalarial breakthroughs in decades has described how a new compound called T111 could transform the global fight against malaria by attacking the parasite across all three stages of its lifecycle simultaneously, potentially replacing multi-dose drug regimens with a single treatment capable of curing patients, preventing relapse and halting community transmission.
Dr. Jane X. Kelly, Research Professor of Chemistry at Portland State University, who began investigating the acridone chemical class in 2009, told NewsGhana the discovery carries profound implications for sub-Saharan Africa, where the global burden of malaria is most heavily concentrated and where rising drug resistance is undermining existing treatment strategies.
Speaking to NewsGhana on the mechanism behind T111, Kelly explained that the compound targets the Plasmodium mitochondrial electron transport chain, a metabolic pathway essential for parasite survival across every stage of its lifecycle. This sets it apart fundamentally from atovaquone, the only existing antimalarial that engages the same pathway. While parasites develop resistance to atovaquone within weeks under laboratory conditions, Kelly told NewsGhana it took 16 to 18 months of sustained selection pressure to generate resistance to T111 in experimental settings. Critically, T111 does not trigger the specific mutation that renders atovaquone ineffective and retains full potency against parasites already resistant to atovaquone, artemisinin and chloroquine.
“Drug resistance is one of the most urgent threats to malaria control globally,” Kelly told NewsGhana, noting that artemisinin partial resistance, first identified in Southeast Asia, has already been detected in multiple African countries including across East Africa.
Kelly explained to NewsGhana that T111’s action on dormant liver-stage parasites addresses one of the most persistent gaps in existing malaria treatment, namely the ability of the parasite to hide in the liver and re-emerge to cause relapse months or even years after an initial infection. By simultaneously targeting sexual-stage gametocytes, the form mosquitoes pick up during blood meals, T111 can interrupt community-level transmission rather than simply treating individual cases. The World Health Organization (WHO) has identified this multi-stage activity profile as a priority target for malaria elimination efforts globally.
On the path to patients, Kelly told NewsGhana that T111 is currently in late pre-clinical development. A prodrug formulation designed for oral delivery is being evaluated in non-human primate studies through a collaboration with the Walter Reed Army Institute of Research and the Armed Forces Research Institute of Medical Sciences. A long-acting injectable form for prevention and prophylaxis is also under active investigation. The next critical step, she said, involves investigational new drug (IND)-enabling studies covering formal toxicology, pharmacokinetics and manufacturing requirements before human trials can begin, leading to Phase 1 trials in healthy volunteers and Phase 2 efficacy studies in malaria-endemic populations.
Asked about wider applications, Kelly told NewsGhana the acridone chemical class has also demonstrated activity against Toxoplasma gondii and Babesia species, pointing to broader potential across related parasitic diseases affecting vulnerable populations.
The research, involving 58 co-authors across more than a dozen institutions on four continents, drew on partnerships with the Eck Institute for Global Health at the University of Notre Dame, the University of Melbourne, the Harvard T.H. Chan School of Public Health, Oregon Health and Science University, the National Institutes of Health and collaborators conducting studies on clinical parasite isolates from patients in Uganda.
