Pliant Therapeutics Reports Positive Phase 2a Trial Results for Bexotegrast in Idiopathic Pulmonary Fibrosis

Pliant Therapeutics, Inc. has revealed promising results from a 12-week clinical trial of bexotegrast (PLN-74809) in patients with idiopathic pulmonary fibrosis (IPF). This study, conducted at Massachusetts General Hospital, was a randomized, double-blind, placebo-controlled trial aiming to assess the changes in total lung collagen levels.

IPF is a progressive lung disease marked by excessive collagen buildup, leading to fibrosis and impaired lung function. The trial enrolled ten patients, seven of whom received bexotegrast at a daily dose of 160 mg, while the remaining three received a placebo. Most participants were on standard IPF treatments, mainly nintedanib.

The primary endpoint was to evaluate the change in total lung collagen using positron emission tomography (PET) imaging with a collagen-binding radiotracer, 68GA-CBP8. Results showed that patients treated with bexotegrast exhibited a reduction in total lung collagen levels as indicated by a decrease in standardized uptake value (SUV), whereas the placebo group saw an increase in SUV. This suggests that bexotegrast might have a potential antifibrotic effect, reversing the fibrosis process.

In addition to collagen reduction, the trial also assessed exploratory efficacy endpoints, including forced vital capacity (FVC), forced vital capacity percent predicted (FVCpp), patient-reported cough severity, and biomarkers related to fibrosis. Bexotegrast-treated patients demonstrated improvements in lung function (increased FVC and FVCpp) and a reduction in cough severity at all timepoints compared to those on placebo. Chronic cough is a significant symptom in IPF, often indicating disease progression and increased mortality risk.

Moreover, the study monitored biomarkers such as integrin beta-6 and PRO-C3, both associated with IPF progression. At Weeks 4 and 12, patients on bexotegrast showed reduced levels of these biomarkers relative to the placebo group, further suggesting that the drug may positively influence disease progression.

The secondary endpoint focused on the safety and tolerability of bexotegrast. Over the 12-week period, the drug was well tolerated, with no serious adverse events or discontinuations reported. Most treatment-emergent adverse events (TEAEs) were mild in severity.

“These imaging data continue to demonstrate the antifibrotic mechanism of action of bexotegrast and build on previous results, including from our INTEGRIS-IPF Phase 2a trial,” stated Éric Lefebvre, M.D., Chief Medical Officer at Pliant Therapeutics. Sydney Montesi, M.D., the Principal Investigator in the trial, highlighted the pioneering use of collagen PET imaging to assess therapeutic intervention, emphasizing its potential in identifying disease-modifying antifibrotic therapies for IPF.

In summary, the 12-week trial of bexotegrast in IPF patients has yielded significant findings. The drug demonstrated potential in reducing total lung collagen, improving lung function, alleviating cough, and lowering fibrosis biomarkers, all while being well tolerated. These results indicate that bexotegrast could be a promising therapeutic option for patients with IPF, warranting further studies to confirm its efficacy and safety in a larger patient population.