Chasing Boehringer, Pliant sends stock soaring with midphase fibrosis data

Pliant Therapeutics’ bid to upend the idiopathic pulmonary fibrosis (IPF) market is gathering pace. The latest phase 2a data drop suggests dialing up the dose boosts efficacy without compromising safety, prompting investors to send shares in the biotech spiraling upward.  

Bexotegrast is an oral dual selective inhibitor of alpha V beta 1 and alpha V beta 6. Evidence that the integrins promote fibrosis through TGF-beta activation has attracted multiple research teams, with mixed results. AbbVie entered the space in 2020 through a deal with Morphic Therapeutic, only to pull the plug on its collaboration over a suspected on-target, αvβ6-mediated safety signal 11 months ago.

Pliant allayed concerns that it would be sunk by similar problems last summer with the release of data on the first three dose cohorts in its phase 2a trial. Now, the biotech is back with the results of its fourth, and highest, dose. 

After 12 weeks of taking daily, 320-mg doses of bexotegrast, the 21 people in the fourth arm underwent a mean 29.5-mL increase in forced vital capacity (FVC), a measure of lung function. The 30 participants who received placebo across the study experienced a 110.7-mL decline in FVC over the same period. While the efficacy endpoint was exploratory, Pliant said the difference over placebo was statistically significant. 

The biotech also linked bexotegrast to statistically significant improvements in FVC after four and eight weeks. The change in FVC decreased over the course of the trial, peaking at 101.7 mL after four weeks of treatment. Data through to Week 24 are due in the second quarter of the year.

On the safety front, no patients in the high-dose arm reported drug-related severe or serious adverse events. All drug-related adverse events were mild or moderate in severity. Investors responded to the data by sending shares in Pliant up over 50% to around $35 in premarket trading.

The jump reflects rising confidence that bexotegrast has a shot at improving on the current treatments for IPF. Today, Roche’s Esbriet and Boehringer Ingelheim’s Ofev compete for the U.S. market. Generic copies of Esbriet are already available, and Ofev is set to lose patent protection in 2025. 

Boehringer has a new molecule, BI 1015550, in phase 3 development. Bexotegrast triggered a bigger FVC improvement after 12 weeks than BI 1015550 did, but the small numbers of participants and general issues with the reliability of cross-trial comparisons leave scope to question whether the existing data are an accurate reflection of the merits of the molecules.