Leishmaniasis is a severe public health issue and the current treatments are toxic, costly or lead to parasite resistance, thus there is an urgent need for new drugs. The TEXLEISH consortium proposes a new paradigm: inhibiting host-parasite interactions, through targeting Leishmania exoproteome, in order to limit the risk of parasite resistance. TEXLEISH synergizes important expertise in medicinal chemistry, kinase-based drug discovery, parasite biology and in vivo testing to optimize CTN1122, a potent antileishmanial lead compound, into an orally active, safe, effective drug candidate. This process involves iterative rounds of chemical synthesis, assessment of its efficacy, toxicity, in vitro bioavailability, in vivo efficiency on animal models and the study of its mechanism of action. The TEXLEISH project will constitute a proof of concept to validate pathogen exoproteome as the future of target-based strategies.