Osteoarthritis (OA) is a debilitating disease of the joints, characterized by local inflammation and degradation of the articular cartilage.Currently, there are no approved disease modifying osteoarthritis drugs (DMOADs) on the market and thus represents a major unmet medical need.Worldwide, OA inflicts 100s of millions of people and that number is increasing as the population ages and becomes more obese.At GIBH we have identified two key drivers of inflammation and articular cartilage degradation and developed siRNA-conjugates targeting these genes as novel intra-articular therapeutics that effectively block their expression as well as demonstrate a long retention time in the articular cavity.This bio-surgery approach has been validated in an aggressive model of inflammatory arthritis and has demonstrated excellent prophylactic and therapeutic efficacy.Safety evaluation of the intra-articular DMOAD shows a clean profile.Both manufacturing and formulation of the therapeutic agent has been validated and quality controlled and current data suggest that once a quarter dosing in people may be possible.IND enabling activities for the DMOAD has been initiated.