We prioritize quantifying synovial-fluid and tissue pharmacokinetics in large-animal osteoarthritis models with phenolic payloads and adding imaging readouts for joint residency; aligning mechanisms to clinically meaningful endpoints by pairing pain and function with MRI measures of cartilage and bone-marrow lesions and by including soluble biomarkers that track NF-κB/Nrf2 activity; and standardizing dose and formulation reporting, including CMC attributes, release kinetics, and batch variability, to enable reproducible dosing across studies. The gene discussed is NFKB1; the disease is osteoarthritis.