Phase 2a Trial Shows GRI-0621 Improves Biomarkers and Lung Repair in IPF

A phase 2a clinical trial evaluating the oral therapy GR-0621 for treating idiopathic pulmonary fibrosis (IPF) demonstrated positive flow cytometry data, marking a significant step forward in addressing the unmet needs of the disease.1

GRI-0621 is an experimental oral therapy manufactured by GRI Bio, a clinical-stage biopharmaceutical company focused on innovations to treat inflammatory, fibrotic, and autoimmune diseases. Its therapies are designed to target the activity of natural killer T cells (NKT). GRI-0621 is an RARβy agonist that inhibits the activity of the type I invariant NKT (iNKT), which plays a critical role in propagating the injury, inflammatory response, and fibrosis observed in inflammatory and fibrotic indications. Earlier data from the clinical trial (NCT06331624) evaluating GRI-0621 showed that it met its primary and secondary end points, demonstrating that GRI-0621 was safe and efficacious over the 12-week treatment period.2 The additional data released this month showed that the agent was associated with iNKT inhibition and may also help reduce inflammation and fibrotic activity in the lungs.1

A Phase 2a trial found GRI-0621 safe and associated with biomarker improvements suggesting reduced fibrosis and lung tissue repair in IPF. | Image credit: @Ahmad-AdobeStock.jpeg

“There remains a tremendous unmet need for safe, tolerable, and truly effective treatments for patients suffering from IPF,” Marc Hertz, PhD, CEO of GRI Bio, said in a press release.

The randomized, double-blind, multicenter study enrolled 35 participants with IPF and randomized them 2:1 to receive GRI-0621 or a placebo. There were no safety or tolerability concerns observed at 12 weeks or during treatment. The most common adverse events reported were dry skin, dry lips, and muscle and joint pain. The GRI-0621 arm outperformed the placebo control arm with no increase in cough (0% in the GRI-0621–treated arm vs 25% in the placebo arm).2 Furthermore, there were significantly fewer reports of gastrointestinal disorders in the GRI-0621 arm compared with the placebo arm (diarrhea reported in 13% vs 33%, respectively).

The secondary end points showed improvements in the serum biomarkers of collagen turnover. Researchers said these findings suggest this treatment may reverse fibrosis and repair damaged lung tissue. Patients in the GRI-0621 arm saw a 3% decrease in Pro-C6—a biomarker of collagen synthesis—and a 12% increase in C6M—a biomarker of collagen degradation—compared with the placebo arm.

Furthermore, the study observed an increase in biomarkers suggesting GRI-0621 was helping to rebuild the alveolar basement membrane in patients with IPF—a common adverse event associated with the disease. Patients randomized to the GRI-0621 arm experienced a mean increase of PRO-C4—a biomarker of type IV collagen synthesis—of 9% whereas patients in the placebo arm experienced a decrease of 2%.

Patients in the GRI-0621 arm also experienced a decrease in C4Ma3—a biomarker of type IV collagen degradation—whereas those in the placebo arm experienced an increase (10% vs 24%, respectively). Thus, GRI-0621–treated patients’ collagen remodeling status shifted from fibrolytic to neutral, meaning there was no continued destruction of the basement membrane.

Overall, 39% of GRI-0621–treated participants experienced an increase in forced vital capacity (FVC) at 12 weeks, whereas 80% of participants in the placebo-treated arm experienced a decline in FVC at 12 weeks.

“The positive Phase 2a results represent an important milestone for our IPF program and a compelling early signal of GRI-0621’s disease-modifying potential,” Hertz said in the December press release. “IPF remains one of the most devastating respiratory diseases, with limited treatment options and a significant need for therapies that can do more than slow decline and address the underlying biology of the disease.”

References:

1. Gri Bio announces additional positive data from phase 2A study in idiopathic pulmonary fibrosis, strengthening clinical proof-of-concept for GRI-0621. News release. GRIbio. January 8, 2026. Accessed January 20, 2026. https://gribio.com/gri-bio-announces-additional-positive-data-from-phase-2a-study-in-idiopathic-pulmonary-fibrosis-strengthening-clinical-proof-of-concept-for-gri-0621/

2. Gri Bio announces positive topline data from its phase 2A study in idiopathic pulmonary fibrosis (“IPF”). News release. GRIbio. December 10, 2025. Accessed January 20, 2026. https://gribio.com/gri-bio-announces-positive-topline-data-from-its-phase-2a-study-in-idiopathic-pulmonary-fibrosis-ipf/