Pliant slumps on decision to pause lung disease drug trial

Shares in Pliant Therapeutics plunged in after-hours trading after the US biotech revealed that it has paused a phase 2b/3 trial of its lead drug for idiopathic pulmonary fibrosis (IPF) after seeing a safety signal.

The South San Francisco company said it acted on the advice of the trial's independent data safety monitoring committee, implementing an immediate halt on both patient enrolment and dosing. Its shares were down nearly 35% at the time of writing.

The decision affects the BEACON-IPF trial of integrin inhibitor bexotegrast, which showed promise in IPF in the phase 2 INTEGRIS-IPF trial reported in 2023. The drug is a dual-selective inhibitor of αvβ6 and αvβ1 integrins, which are seen in elevated levels in the lung tissue of IPF patients and are thought to promote fibrosis (scarring) in the progressive disease.

IPF is an incurable disease where the lungs become increasingly damaged by scar tissue, resulting in breathing getting progressively more difficult, and is generally considered a terminal illness.

In a statement, Pliant said that patients will remain in the trial, which will continue to be blinded, while the data is reviewed and it tries to "understand the [committee's] rationale for their recommendation."

The phase 2b stage of the 52-week BEACON-IPF trial had been scheduled to complete enrolment in the first quarter of this year, with data expected in the middle of 2026, and investors will be waiting to see what the implications of the pause will be on the future of the programme as well as that timeline.

Other integrin inhibitors in development for IPF have also run into trouble because of safety issues, notably Biogen's BG00011 (also known as STX-100), which was abandoned after reaching phase 2b.

Encouraging data with bexotegrast, which has a fast-track designation from the FDA, has allowed Pliant to raise considerable funding in recent years, and it ended the third quarter of last year with more than $400 million in cash reserves. Its most recent financing came in 2023 when it pulled in gross proceeds of almost $288 million from an upsized public offering.

In the 119-patient INTEGRIS-IPF trial, the drug achieved a reduced decline in forced vital capacity (FVC) – a measure of lung function – compared to placebo, when added to standard IPF therapy with Boehringer Ingelheim's Ofev (nintedanib) or Roche's Esbriet (pirfenidone).

Pliant is also developing a follow-up integrin inhibitor codenamed PLN-101095 that targets αvβ8 and αvβ1 and has potential as a cancer therapy, although that is back in phase 1 testing. It is also preparing to start a phase 1 study of PLN-101325, an antibody agonist of integrin α7β1 for muscular dystrophies.