Pliant Therapeutics Shares Halted After Bexotegrast Phase 2b Trial Discontinued

Pliant Therapeutics, Inc. (Nasdaq: PLRX) shares were halted in early morning trading on March 3, 2025, after falling 25% to $2.57, following the company's announcement that it has discontinued a phase 2b trial for its lead drug candidate, bexotegrast, in patients with idiopathic pulmonary fibrosis (IPF). The trial, known as BEACON-IPF, was stopped due to safety concerns, despite showing early evidence of efficacy on the forced vital capacity (FVC) endpoint.

The discontinuation of the BEACON-IPF trial comes after a prespecified data review and recommendation by the trial's independent Data Safety Monitoring Board (DSMB), as well as a secondary review and recommendation by an outside expert panel. While an imbalance in unadjudicated IPF-related adverse events between the treatment and placebo groups led to the discontinuation of the trial, early evidence of efficacy on the FVC endpoint was also observed.

The mean exposure duration in BEACON-IPF was approximately 17 weeks. Overall, the percentage of IPF-related adverse events in both dose groups was comparable, around 10%. However, the imbalance between active and placebo groups appears to have been driven by an unusually low IPF-related adverse event rate in the placebo group, which was below 3%. In comparison, the Phase 2a INTEGRIS-IPF trial showed comparable IPF-related adverse event rates between bexotegrast-treated (7%) and placebo-treated (10%) participants, with a mean exposure duration of approximately 16 weeks.

Pliant Therapeutics plans to analyze the complete data from the BEACON-IPF trial and evaluate next steps for bexotegrast's development. Once the full analysis is completed, the company will consider additional dose-ranging Phase 2b studies with lower doses in pulmonary fibrosis and potentially, other non-respiratory indications, including liver diseases. Pliant is also committed to the development of its other clinical and pipeline assets, including PLN-101095 in oncology, which is currently in Phase 1 trials with interim data expected in the first quarter of 2025.



The discontinuation of the BEACON-IPF Phase 2b trial represents a significant clinical development setback for Pliant Therapeutics, substantially impacting the company's near-term prospects. The trial was stopped due to safety concerns, specifically an imbalance in IPF-related adverse events between treatment and placebo groups, despite showing encouraging efficacy signals on the important FVC endpoint. This paradoxical outcome creates a complex scenario for investors to evaluate, as the company appears to be pivoting toward exploring lower doses in future studies to maintain efficacy while improving safety.

The 17-week mean exposure duration in the trial provides long-term safety data, complicating the risk assessment. Notably, the company pointed out that the adverse event imbalance may have been partially driven by an unusually low event rate (3%) in the placebo arm, rather than solely by toxicity in the treatment arms. Investors should closely monitor the upcoming complete data analysis, which will determine whether bexotegrast has a viable path forward at lower doses or if resources will shift more decisively toward their oncology asset PLN-101095.

The discontinuation of BEACON-IPF highlights the significant challenges in developing effective IPF therapies. What's clinically interesting is that this appears to be the first late-stage IPF trial discontinued for safety while simultaneously demonstrating strong efficacy signals on FVC - the gold standard endpoint for IPF trials. The approximately 10% rate of IPF-related adverse events in the treatment arms compared to below 3% in the placebo group represents a concerning safety signal. However, this must be contextualized with their Phase 2a INTEGRIS-IPF data, which showed comparable adverse event rates between bexotegrast (7%) and placebo (10%) participants.

For a devastating disease like IPF with limited treatment options, finding the optimal therapeutic window is critical. The company's strategy to potentially explore lower doses makes clinical sense, as IPF drug development often requires careful dose optimization to balance efficacy and tolerability. The fact that they're considering non-respiratory indications like liver diseases also indicates potential mechanistic versatility of their αvβ6 integrin inhibitor approach.



In conclusion, Pliant Therapeutics faces a significant challenge in the development of bexotegrast for IPF, as the drug's safety profile has raised concerns despite showing early efficacy signals. The company's strategic considerations, including potential dose-ranging Phase 2b studies and exploration of non-respiratory indications, will be crucial in determining the drug's future and the company's overall pipeline progress. Investors should closely monitor the upcoming complete data analysis and the company's next steps in the development of bexotegrast and other pipeline assets.