Pliant Therapeutics, Inc. announced 12-week interim data from the 320 mg dose group of INTEGRIS-IPF, a multinational, randomized, double-blind, placebo-controlled Phase 2a clinical trial of bexotegrast (PLN-74809) in patients with idiopathic pulmonary fibrosis (IPF). The 320 mg group met its primary and secondary endpoints demonstrating that bexotegrast was well tolerated over a 12-week treatment period and displayed a favorable pharmacokinetic profile. The trial's exploratory efficacy endpoints assessed changes in forced vital capacity (FVC), Quantitative Lung Fibrosis (QLF) imaging and biomarkers.

Bexotegrast at 320 mg demonstrated a statistically significant mean increase in FVC from baseline at all timepoints, surpassing all lower dose cohorts, and showed a strong treatment effect on FVC percent predicted (FVCpp), QLF and profibrotic biomarkers versus placebo at 12 weeks. The INTEGRIS-IPF Phase 2a trial is evaluating bexotegrast at once-daily doses of 40 mg, 80 mg, 160 mg, 320 mg or placebo for 12 weeks in 119 patients with IPF. The 320 mg group enrolled 21 patients in the active arm and 8 patients in the placebo arm.

Comparable to the lower dose groups, approximately 80% of all enrolled patients were on standard of care and were equally distributed between nintedanib and pirfenidone. The 320 mg group will continue until all patients have been treated for at least 24 weeks, with final data expected in the second quarter of 2023. The primary endpoint of the INTEGRIS-IPF trial is the evaluation of the safety and tolerability of bexotegrast.

The secondary endpoint is an assessment of its pharmacokinetics. Bexotegrast was well tolerated at 320 mg over 12 weeks of treatment with no drug-related severe or serious adverse events (SAEs) reported. All drug-related adverse events were mild or moderate in severity.

Bexotegrast exhibited dose-proportional increases in plasma concentrations, consistent with prior studies. The exploratory efficacy endpoints of the INTEGRIS-IPF trial measured changes in FVC, high-resolution CT (HRCT)-based QLF, and profibrotic biomarkers over 12 weeks of treatment. A strong dose-dependent treatment effect was observed in the bexotegrast 320 mg dose group, with and without standard of care therapy.

The bexotegrast 320 mg group demonstrated mean FVC increase of +29.5 mL relative to baseline at 12 weeks, versus a decline of 110.7 mL in the placebo group resulting in a 140 mL increase compared to placebo. Mean increases in FVC versus placebo reached statistical significance at all timepoints. A decline of =10% in FVCpp at 12 weeks has been associated with increased mortality in IPF patients over a two-year period.

Over 12 weeks of treatment, no patients in the 320 mg group experienced =10% decline in FVCpp. An increase in QLF score has been associated with worsening of pulmonary fibrosis. The mean percentage change in QLF at 12 weeks was 0.20% in the 320 mg group versus 1.46% in the placebo group.

PRO-C3, a serum biomarker of type III collagen synthesis, is elevated in patients with IPF and associated with progressive disease.4 The 320 mg group demonstrated a reduction in PRO-C3 at both 4 (p <0.01) and 12 weeks versus placebo. Elevated integrin beta-6 plasma levels have been associated with ILD progression as defined by mortality, transplant or = 10% relative reduction in FVC (mL) over 12 months.5 The 320 mg group demonstrated a reduction in integrin beta-6 at both 4 and 12 weeks (p <0.0001 at both timepoints) versus placebo. These findings support a potential dose-dependent antifibrotic effect of bexotegrast, consistent with its mechanism of action and preclinical findings.

Data from the 320 mg group of the INTEGRIS-IPF trial in patients treated for at least 24 weeks are expected in the second quarter of 2023. Pliant is planning to initiate a Phase 2b clinical trial of bexotegrast in mid-2023. Trial details will be shared closer to initiation.

INTEGRIS-IPF is a Phase 2a, randomized, dose-ranging, double-blind, placebo-controlled trial evaluating the safety, tolerability, and pharmacokinetics of PLN-74809 administered in patients with IPF. Patients were enrolled in doses of 40 mg, 80 mg, 160 mg or 320 mg with a 3:1 randomization ratio (active:placebo) and stratification based on use of standard of care therapy. The primary endpoint is the evaluation of PLN-74809 safety and tolerability and the secondary endpoint is the assessment of pharmacokinetics across a dose range.

Exploratory endpoints will measure change in Forced Vital Capacity (FVC), HRCT-based Quantitative Lung Fibrosis (QLF) score and selected biomarkers. IPF is a chronic, progressive, fibrosing lung disease of unknown cause with few treatment options and a poor prognosis. Patients experience debilitating symptoms, including shortness of breath and difficulty performing daily activities, such as walking and talking.

Currently, there is no pharmacological cure for IPF, with neither of the approved two therapies demonstrating an ability to stop the progression of IPF. Therefore, there is a high unmet need for new therapeutic options to address the symptoms and modify the disease progression of this grievous illness.