High-dose hit sees Pliant push on in lung fibrosis

An earlier cut of the phase 2a Intergris-IPF trial contained an odd dose response that raised questions about bexotegrast (PLN-74809) in idiopathic pulmonary fibrosis. New higher-dose data have erased concerns for some: Pliant shares surged 54% in early trading, worth $500m in market cap. Forced vital capacity, a measure of lung function, significantly increased in patients treated with bexotegrast 320mg at 12 weeks, versus a decline in the placebo group. The magnitude of benefit beat expectations but the shape of the FVC curve prompted headscratching, with a surprisingly steep and early benefit fading away; on a call Pliant executives pointed to three "high responders" dropping out after four weeks. The developer also revealed activity, and a dose response, on biomarkers that it claims supports bexotegrast’s mechanism of action, described as inhibition of the integrins αvβ6 and αvβ1. No serious drug-related events emerged. Small patient numbers are a big caveat to interpreting these findings: only 21 patients were treated with 320mg, and 24-week readout, due in the second quarter, remains important. Pliant plans to start phase 2b around mid-year rather than pushing straight into phase 3 – this is prudent given that IPF has thwarted many apparently promising projects.