Pliant Therapeutics announces data from INTEGRIS-PSC Phase 2a trial

Pliant Therapeutics announced 12-week interim data from the 320 mg dose group of INTEGRIS-PSC, a multinational, randomized, double-blind, placebo-controlled Phase 2a clinical trial of bexotegrast in patients with primary sclerosing cholangitis and suspected moderate to severe liver fibrosis. The 320 mg group met its primary and secondary endpoints demonstrating that bexotegrast was well tolerated over a 12-week treatment period and its plasma concentrations increased with dose. There was no dose relationship for adverse events. Pruritus and cholangitis occurred less frequently on bexotegrast than on placebo. The trial’s exploratory efficacy endpoints assessed changes in the liver fibrosis markers, Enhanced Liver Fibrosis score and PRO-C3 levels, as well as liver biochemistry and magnetic resonance imaging of the liver. Consistent with the results from the lower doses tested, bexotegrast-treated patients at the 320 mg dose showed a reduction in both ELF score and PRO-C3 levels relative to placebo at Week 12. Bexotegrast-treated patients also showed stabilization of alkaline phosphatase levels, relative to an increase on placebo at Week 12. In addition, MRI imaging continued to show evidence of improved hepatocyte function and bile flow with bexotegrast at the 320 mg dose relative to placebo. Bexotegrast at the 320 mg dose was well tolerated with no dose relationship observed for adverse events. Of the 27 patients treated with bexotegrast at the 320 mg dose, 26 completed 12 weeks of treatment with no drug-related severe or serious adverse events. Most treatment-emergent adverse events were mild or moderate in severity and consistent with PSC disease symptoms. In addition, adverse events of pruritus and cholangitis occurred less frequently on all doses of bexotegrast relative to placebo. Patients in the trial who had concomitant inflammatory bowel disease saw no change in their IBD symptoms as measured by partial Mayo Score while on treatment. Consistent with the lower doses tested, bexotegrast at 320 mg reduced ELF score relative to placebo at Week 12. The ELF score is a well-established prognostic marker of liver disease severity and liver-related events in patients with advanced fibrosis. ELF is strongly associated with transplant-free survival in PSC and may be useful as a surrogate marker in clinical trials. Consistent with the lower doses tested, bexotegrast at 320 mg reduced PRO-C3 levels relative to placebo. PRO-C3 is a biomarker of active fibrogenesis with higher levels associated with greater disease activity. The Company is planning to share these data from the INTEGRIS-PSC trial with regulatory authorities to discuss the potential path to registration.