Pliant Therapeutics, Inc. announced that it presented Phase 2a clinical data and preclinical data of bexotegrast (PLN-74809) this week as part of the American Thoracic Society (ATS) 2023 International Conference, held from May 19 through May 24, 2023. In an oral presentation, Lisa H. Lancaster, M.D., Professor of Medicine at Vanderbilt University Medical Center and principal investigator of the INTEGRIS-IPF Phase 2a trial, reviewed 12-week data from the trial. Results showed that bexotegrast was well tolerated across all four dose groups with bexotegrast-treated participants experiencing a reduction in forced vital capacity (FVC) decline over 12 weeks versus placebo, on and off background therapy.

A dose-dependent downwards trend was observed in the proportion of participants with forced vital capacity precent predicted (FVCpp) decline =10%, a well-established predictor of death and disease progression in IPF. Qualitative lung fibrosis (QLF) imaging showed a dose-dependent antifibrotic effect with no or limited progression at the two highest doses and a decrease in serum biomarkers of collagen synthesis (PRO-C3 and PRO-C6) and ITGB6 was observed relative to placebo. Fibrotic human precision-cut lung slices were cultured to investigate the individual and combined effects of bexotegrast and nintedanib or pirfenidone on the expression of genes related to the pathogenesis of idiopathic pulmonary fibrosis (IPF).

Results from a differential gene expression analysis suggest the mechanism of action of bexotegrast may be both independent of, and complementary to, that of currently approved therapies. In an oral presentation, Mahru, An, Ph.D., Principal Scientist at Pliant presented results from a study examining fibrotic human precision-cut lung slices that were treated with bexotegrast, a dual aVß6/aVß1 integrin inhibitor, to assess the effect of pro-fibrotic gene expression levels thought to be important in fibrotic diseases, including IPF. Bexotegrast demonstrated reductions in pro-fibrotic gene expression within unique cell populations including on a number of CTHRC1-high expressing fibroblasts, pro-fibrotic genes, including COL1A1 and VIM, and in aVß6-expressing aberrant basaloid cells that reside adjacent to areas of acute lung injury.

Results also demonstrated the utility of combining single cell transcriptomic techniques with fibrotic human tissue to evaluate the mechanism of action of novel anti-fibrotic therapies, such as bexotegrast.