SBIR Topic 131: Development of Bacteriophage for Treatment of Mycobacterial Infections

Vulcan Biologics is developing an enhanced phage therapy technology as an alternative treatment for non-tuberculous mycobacterium infection, targeting Mycobacterium abscessus, which poses a growing concern and challenge due to its ability to survive within immune cells like macrophages. It is also capable of rapidly developing resistance to antibiotics, limiting the effectiveness of current treatments. We are engineering phages to penetrate both epithelial and immune cells, allowing them to infect intracellularly located target bacteria. We will explore multiple avenues for modifying the phage to display cell-penetrating peptides (CPPs) on its capsid surface. Initially, we will create a selection of bacteriophages and their corresponding susceptible M. abscessus strains. We will focus on a naturally lytic phage named Muddy, previously shown to improve clinical outcomes in a cystic fibrosis patient with disseminated M. abscessus infections in combination with other two engineered phages. Engineered bacteriophages will then be assessed for their ability to internalize within mammalian cells including alveolar epithelial cells and alveolar macrophages. Phages demonstrating the highest internalization efficiency will undergo further testing to evaluate their ability to infect and kill intracellular bacteria. Success will provide the basis for a Phase II study to test additional engineered mycobacteriophages, enable co-administration of antibiotics, test against clinical isolates, and initiate pre-clinical testing in in vivo models, advancing this innovative phage therapy approach towards practical clinical applications.