Preclinical and Clinical Pharmacokinetics of JNJ‐75220795, an siRNA Therapeutic Targeting PNPLA3, for Metabolic Dysfunction‐Associated Steatohepatitis

and AUC increased approximately dose proportionally. Kidney had the second highest tissue exposure following the liver in rats. Renal excretion was a significant but minor elimination pathway as approximately 15%-25% of the administered dose was recovered in urine. Based on the overall data, JNJ-75220795 was primarily localized to the liver and exhibited sustained hepatic exposures, which confer prolonged pharmacodynamic effects in the target organ. The favorable PK profiles of single subcutaneous doses observed in the phase 1 studies support continued clinical development of JNJ-75220795 for the treatment of MASH.