INHALED DELIVERY OF CLOFAZIMINE - A HIGH EFFICIENCY, FLOW INDEPENDENT, TARGETED, LOW COST DPI

Multidrug resistance tuberculosis (MDR-TB) is a global healthcare concern compounded by poor compliance associated with lengthy drug susceptible TB (DS-TB) treatment regimens. Clofazimine (CFZ) is highly active against MDR-TB, but oral use is limited by systemic toxicity (hyperpigmentation, GI effects, and QT prolongation). Inhalation of CFZ will overcome these limitations by achieving high local concentrations of drug and reducing systemic side effects. Based on our strong preliminary data we propose to develop a low-cost, simple to use, alveolar macrophage targeted, and efficient DPI that provides reproducible delivery regardless of inhalation force. Our specific aims are: SA1 - Development of a well-defined formulation and delivery platform for the developed formulation, SA2 - Conduct scale up batches, powder filling, batch variability, SA3-Preclinical in vivo testing in a validated small animal model and SA4 -IND enabling toxicity studies. The result will be a device-drug combination system ready for submission of an IND and Phase 1 clinical testing in humans. The product will be optimized for cost-efficient manufacturing and efficient lung delivery which will enable the company to pursue multiple therapeutic indications each with a viable commercial potential (e.g. MDR-TB, DS-TB, and NTM lung infections)