•Osteoarthritis (OA) patients are in need of new, disease-modifying drugs.•Disease-modifying OA drugs could target cartilage repair or degradation pathways.•Development of intra-articular OA drugs is associated with unique challenges.•OA drug candidate dosing strategy is defined regardless of administration route. Osteoarthritis (OA) is a common disease worldwide with large unmet medical needs. To bring innovative treatments to OA patients, we at Merck have implemented a comprehensive strategy for drug candidate evaluation. We have a clear framework for decision-making in our preclinical pipeline, to design our clinical proof-of-concept trials for OA patients. We have qualified our strategy to define and refine dose and dosing regimen, for treatments administered either systemically or intra-articularly (IA). We do this through preclinical in vitro and in vivo studies, and by back-translating results from clinical studies in OA patients.