Development of a sustained release injectable formulation for long-term delivery of ELQs

The Medicines for Malaria Venture (MMV) recently published a “roadmap” for the types of medicines that are needed to support the long- term goal of malaria eradication. The roadmap consists of a wish list of target candidate profiles (TCP) and medicines (target product profiles, i.e., TPP). With the most recent revision to the anti- malarial target candidates and product profiles the MMV highlighted the need for identifying new medicines for chemo- protection and chemo- prevention with long- acting molecules, and/or parenteral formulations (i.e., TCP- 2) (Burrows, JN et al., 2017, Malaria Journal, 16:26). According to their updated roadmap new drugs are needed to protect populations entering areas of high endemicity during the final stages of malaria elimination. And drugs with causal liver- stage activity are needed for chemoprevention to prevent infection or outbreak of resistance during malarial seasons. This TCP has been modeled on the combination drug atovaquone + proguanil. The MMV envisions that an injectable sustained- release formulation could be developed as a long- acting preventative providing up to 3 to 4 months of protection. As a potent and selective inhibitor of the parasite’s cytochrome bc1 complex, ELQ- 300 targets Plasmodium falciparum in the blood and liver stages and even kills parasites developing in the midgut of the mosquito vector. With support from the NIH and US DOD there has been success in developing an oral formulation of prodrug ELQ- 331 for use in humans for weekly prophylaxis against malaria, work that was performed in collaboration with SRI International. In collaboration with SRI International existing knowledge of ELQ- 300 prodrug chemistry, crystallinity, stability, and solvent/vehicle solubility will be leveraged with their expertise in formulation design and optimization to identify the optimal ELQ- 300 prodrug design that is paired with an optimal depot formulation to provide long- term protection of animals from sporozoite infection. Four different prodrug chemistries will be evaluated and compared, varying R- group chain length to optimize the physiochemical properties of the drug and to enhance solubility in vehicles and mixtures that are approved for human use.

Project detailsDetails on drug developmentMMV pipeline information

Drug-based Strategies
Product Development

Jun 2019 — May 2024

$3.23M

United States