PLN-74809 is a small-molecule that dually inhibits both αβ and αβ to treat both idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC). The compound was granted orphan drug designation by the US FDA in August 2018 for treatment of IPF, and Pliant Therapeutics recently raised $100 million in Series C financing to support further clinical development of this compound. Phase 2a studies are currently evaluating PLN-74809 safety and efficacy for participants with IPF (NCT04396756)across 10 participating countries, and for participants with PSC (NCT04480840). In addition, the compound is also currently in Phase 2a trials (NCT04565249) for the treatment of COVID-19 related acute respiratory distress syndrome.
Through dual inhibition of integrins αβ and αβ, PLN-74809 reduces subsequent activation of TGF-β1, which is actively involved in the growth of fibrotic tissue in lung and bile ducts. Further studies showed that PLN-74809 inhibited collagen gene expression in PSC and IPF patient tissue.
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