Chronic wounds are defined as those that fail to heal through an orderly and timely reparative process (21). Approximately 6.5 million patients are afflicted with chronic wounds in the U.S. each year, and the burden is growing rapidly due to the increasing aging population and the rise in the incidence of diabetes.(22) Chronic wounds result in severe psychological, social, and economic burdens, and the estimated financial cost associated with treating chronic wounds in the U.S is estimated to be $10-$25 billion per year (22,23).

Wound pathogenesis is dependent on multiple factors, including the bacterial species that are present as well as bacterial load (22,24). As with other persistent infections, bacterial colonization in the form of biofilms has been shown to delay healing.25,26,27 Biofilms provide a protective environment for bacteria, increasing their resistance to antimicrobials and to the host immune response. Once established, biofilms are extremely difficult to eradicate, and studies have shown that many topical agents and wound dressings are ineffective against biofilm infections.

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Agile Sciences has developed a novel approach for eradicating biofilms present in chronic wounds. The Company’s 2-AI small molecules exhibit broad bacterial biofilm inhibition and dispersal properties against both Gram-positive and Gram-negative bacteria. The 2-AI molecules act to dismantle the biofilm community into single, free-floating bacteria allowing antimicrobials to work on the planktonic form of the bacteria toward which they are most effective (28,29,30). The 2-AI molecules have been shown to inhibit and disperse bacterial biofilms of strains relevant to chronic wounds, are active under flow conditions, and are non-microbicidal.

Agile Sciences is evaluating the effectiveness of a lead 2-AI compound in combination with silver for use as a topical treatment for chronic wound infections. The lead compound has been shown to have anti-biofilm activities against Staphylococcus aureus and Pseudomonas aeruginosa, two bacteria that are often responsible for chronic wound infections. Additionally, the lead compound has been classified as a non-irritant using an in vitro human tissue mimic. The in vivo efficacy of the lead compound in combination with silver has been investigated using a rabbit ear wound model and a pig wound model.