Pliant Therapeutics Provides Update on BEACON-IPF, a Phase 2b/3 Trial in Patients with Idiopathic Pulmonary Fibrosis

Rhea-AI Summary

Pliant Therapeutics (PLRX) has discontinued its BEACON-IPF Phase 2b trial of bexotegrast in idiopathic pulmonary fibrosis (IPF) patients following safety concerns, despite showing early efficacy signs in forced vital capacity (FVC). The discontinuation came after reviews by the trial's Data Safety Monitoring Board and an external expert panel.

The trial, with approximately 17 weeks mean exposure duration, showed comparable IPF-related adverse events (around 10%) in both dose groups. However, an imbalance was noted due to unusually low adverse event rates (<3%) in the placebo group. This contrasts with the Phase 2a INTEGRIS-IPF trial, where adverse events were similar between bexotegrast-treated (7%) and placebo groups (10%).

The company plans to analyze the complete data and consider additional Phase 2b studies with lower doses for pulmonary fibrosis and other non-respiratory indications. Meanwhile, Pliant continues developing other assets, including PLN-101095 in oncology, currently in Phase 1 trials.

Positive

• Early evidence of efficacy on forced vital capacity (FVC) endpoint
• Continuing development of PLN-101095 in oncology with Phase 1 trial progress
• Potential expansion to non-respiratory indications including liver diseases

Negative

• BEACON-IPF Phase 2b trial discontinued due to safety concerns
• Imbalance in IPF-related adverse events between treatment and placebo groups
• Need to potentially lower doses, requiring additional Phase 2b studies

Insights

Biotech Research Analyst

Pliant Therapeutics' discontinuation of the BEACON-IPF Phase 2b/3 trial represents a significant clinical development setback that substantially impacts 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 forced vital capacity (FVC) endpoint.

This paradoxical outcome (efficacy with safety concerns) creates a complex scenario for investors to evaluate. The company appears to be pivoting toward exploring lower doses in future studies, suggesting they believe a therapeutic window may still exist where efficacy can be maintained with improved safety. However, this represents a meaningful delay in their development timeline for bexotegrast.

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, currently in Phase 1 with interim data expected in Q1 2025.

Pulmonary Medicine Specialist

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 placebo 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%).

This discrepancy between trials suggests potential variability in patient populations or disease progression that complicates interpretation. It's noteworthy that despite the safety concerns, the efficacy signal remained strong enough to mention prominently in this disclosure - suggesting bexotegrast may still have therapeutic potential if the right dose can be identified.

For a devastating disease like IPF with 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.

SOUTH SAN FRANCISCO, Calif., March 03, 2025 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX) today announced that following 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, Pliant has discontinued the BEACON-IPF Phase 2b trial evaluating bexotegrast in patients with idiopathic pulmonary fibrosis (IPF). 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 forced vital capacity (FVC) endpoint was also observed.

BEACON-IPF is the first late-stage IPF trial to be discontinued for safety while showing strong evidence of efficacy.

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 (approximately 10%). The imbalance between active and placebo appears to have been driven by a low (below 3%) IPF-related adverse event rate in the placebo group. In comparison, in the Phase 2a INTEGRIS-IPF trial (mean exposure duration of approximately 16 weeks), IPF-related adverse events were comparable in bexotegrast-treated (7%) across all doses and placebo-treated (10%) participants.

The Company 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, which should provide a better understanding of the benefit risk profile and therapeutic window of bexotegrast, 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 committed to the development of its other clinical and pipeline assets including PLN-101095 in oncology. The Company is currently enrolling the fourth of five planned dose cohorts in a Phase 1 open label dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Interim data from the first three cohorts is expected in the first quarter of 2025.

Pliant would like to thank the BEACON-IPF investigators and their study teams, as well as the members of the Pliant team for their dedication in support of the execution of this trial. The Company also wants to give special thanks to the BEACON-IPF clinical trial participants, their families and support networks for their participation in, and support of BEACON-IPF.

About BEACON-IPF

BEACON-IPF is a 52-week, multinational, randomized, dose-ranging, double-blind, placebo-controlled trial evaluating bexotegrast at once-daily doses of 160 mg or 320 mg in patients with idiopathic pulmonary fibrosis (IPF).

About Pliant Therapeutics, Inc.

Pliant Therapeutics is a late-stage biopharmaceutical company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases. Pliant's lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of α_vß6 and α_vß₁ integrins that is in development in the lead indication for the treatment of idiopathic pulmonary fibrosis, or IPF. Bexotegrast has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and Orphan Drug Designation from the European Medicines Agency in IPF. Pliant is conducting a Phase 1 study for its third clinical program, PLN-101095, a small molecule, dual-selective inhibitor of α_vß₈ and α_vß₁ integrins, that is being developed for the treatment of solid tumors. In addition, Pliant has received regulatory clearance for the conduct of a Phase 1 study of PLN-101325, a monoclonal antibody agonist of integrin α₇β₁ targeting muscular dystrophies.

For additional information, please visit: www.PliantRx.com. Follow us on social media X, LinkedIn, and Facebook.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those regarding the Company’s preliminary analysis of data from the BEACON-IPF trial, the Company’s intent to complete a more full analysis and potential next steps for bexotegrast development, as well as statements regarding the development of the Company’s other clinical and pipeline assets. Because such statements deal with future events and are based on our current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Pliant Therapeutics could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including those related to the development and commercialization of our product candidates, including analysis of the complete data from the BEACON-IPF trial, any delays in our ongoing or planned preclinical or clinical trials, the risks inherent in the drug development process, and our capital requirements and the need for additional financing, including the anticipated lack of availability of additional funds under the current terms of our loan facility. These and additional risks are discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Quarterly Report on Form 10-Q for the period ended September 30, 2024, which is available on the SEC's website at www.sec.gov, as updated by our Annual Report on Form 10-K for the year ended December 31, 2024, which we expect to file with the SEC today. Unless otherwise noted, Pliant is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

Investor and Media Contact:

Christopher Keenan
Vice President, Investor Relations and Corporate Communications
Pliant Therapeutics, Inc.
ir@pliantrx.com

FAQ

Why was the BEACON-IPF Phase 2b trial of bexotegrast (PLRX) discontinued?

The trial was discontinued due to an imbalance in IPF-related adverse events between treatment and placebo groups, despite showing early efficacy in forced vital capacity (FVC).

What were the adverse event rates in PLRX's BEACON-IPF trial compared to placebo?

Both dose groups showed approximately 10% IPF-related adverse events, while the placebo group showed an unusually low rate below 3%.

What are Pliant Therapeutics' (PLRX) next steps for bexotegrast development?

Pliant plans to analyze complete trial data and consider additional Phase 2b studies with lower doses in pulmonary fibrosis and potentially other non-respiratory indications.

What other clinical trials is Pliant Therapeutics (PLRX) currently conducting?

PLRX is conducting a Phase 1 dose-escalation trial of PLN-101095 in oncology, with interim data from the first three cohorts expected in Q1 2025.