GRI-0621 Well-Tolerated, Shows Positive Biomarker and FVC Data in IPF

GRI-0621 was well tolerated by people with idiopathic pulmonary fibrosis (IPF) over a 12-week treatment period, meeting the primary end point of the Phase 2a GRI-0621-IPF-02 clinical trial.1 The trial also met its secondary end point, with treated participants exhibiting improvements in serum biomarkers. More recently, the GRI Bio also announced positive flow cytometry data.2

“Treatment of patients with IPF in the GRI-0621 Phase 2a trial was observed to be safe and well tolerated through the completion of the 12-week study,” Toby Maher, MD, PhD, Professor of Clinical Medicine, Keck School of Medicine, USC Los Angeles, said in a statement.1 “Secondary endpoints related to the effect of GRI-0621 on biomarkers associated with disease progression provided evidence that GRI-0621 maintains a net anti-fibrotic effect compared to standard of care. Lastly, FVC improved in patients treated with GRI-0621, with more patients experiencing an increase at 12 weeks than with standard of care. We look forward to watching the clinical advancement of GRI-0621 as a potential treatment for patients with IPF.”

The phase 2a randomized, double-blind, multinational, multicenter, placebo-controlled, parallel-design study enrolled 35 patients with IPF randomized 2:1 to receive oral GRI-0621 4.5 mg or placebo once daily for 12 weeks. After 12 weeks of treatment, no safety or tolerability concerns were identified among enrolled participants, with dry skin, dry lips, and muscle or joint pain representing the most frequently reported adverse events. Notably, no increases in cough were observed in the GRI-0621–treated group (0%) compared with placebo (25%), and gastrointestinal disorders were less frequent with GRI-0621 than with placebo, including diarrhea reported in 13% versus 33% of patients, respectively. Most participants (80%) were receiving background antifibrotic therapy with pirfenidone or nintedanib.1

Treatment with GRI-0621 was also associated with favorable changes in serum biomarkers of collagen turnover, consistent with fibrosis resolution and activation of alveolar basement membrane repair mechanisms. Levels of PRO-C6, a marker of type VI collagen synthesis, decreased from baseline by 3% in GRI-0621–treated patients but increased by 12% in those receiving placebo plus standard of care. In contrast, C6M, a biomarker of type VI collagen degradation, increased by 6% with GRI-0621 and decreased by 3% with placebo. Overall, the type VI collagen remodeling rate shifted from fibrogenic in the placebo group (+10%, reflecting continued fibrosis progression) to fibrolytic in the GRI-0621 group (−7%, reflecting fibrosis resolution). Reductions in biomarkers of neutrophil and macrophage activity, as well as downregulation of genes associated with fibrosis, disease progression, and mortality, were also observed in GRI-0621–treated patients compared with placebo.1

Placebo-adjusted changes from baseline in FVC showed an increase of 99 mL in the GRI-0621 arm and 139 mL among patients receiving both GRI-0621 and background standard of care. Given the known variability of spirometry, a post hoc analysis excluding extreme FVC outliers demonstrated placebo-adjusted increases of 54 mL in the overall GRI-0621 group and 81 mL in the subgroup on combination therapy. At week 12, 39% of patients treated with GRI-0621 experienced an increase in FVC, whereas 80% of placebo-treated patients experienced a decline.1

“There remains a tremendous unmet need for safe, tolerable, and truly effective treatments for patients suffering from IPF,” Marc Hertz, PhD, Chief Executive Officer of GRI Bio, said.2 “GRI-0621 continues to demonstrate a compelling profile, combining favorable safety and tolerability with a dual mechanism of action as both an immunomodulator and an anti-fibrotic agent.”

More recently, GRI announced that immune cell analyses from bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMCs) showed that GRI-0621 treatment inhibited invariant natural killer T (iNKT) cell activity and drove a clear immunomodulatory shift toward an anti-fibrotic phenotype. Treated patients produced higher levels of the anti-fibrotic cytokine interferon-gamma (IFN-γ) alongside reduced production of pro-fibrotic cytokines, including interleukin-4 (IL-4), IL-13, IL-17A, IL-22, and transforming growth factor-beta (TGF-β).2

Consistent with reduced chronic activation, iNKT cells from GRI-0621–treated subjects demonstrated increased T-cell receptor (TCR) expression after 12 weeks compared with baseline and placebo-treated subjects receiving standard of care. Across both BAL and PBMC samples, T-cell subsets showed increased type 1–associated cytokine expression (IFN-γ) with concomitant reductions in type 2 (IL-4, IL-13) and type 3 (IL-17A, IL-22) cytokines. Reductions in TGF-β were also observed after 12 weeks of GRI-0621 treatment across multiple immune cell populations—including regulatory T cells (Treg and Treg-like), B cells, monocytes, macrophages, and neutrophils—compared with baseline and placebo, further supporting a broad anti-fibrotic immunologic shift.2

“Our Phase 2a study was intentionally designed to assess a broad range of clinical, biomarker, and mechanistic endpoints,” Hertz said.2 “The immune cell data announced today are highly consistent with our earlier findings on collagen turnover, lung tissue repair, and improvements in pulmonary function, further strengthening the overall clinical proof-of-concept for GRI-0621.”

References

1. GRI Bio Announces Positive Topline Data from its Phase 2a Study in Idiopathic Pulmonary Fibrosis (“IPF”). News release. GRI Bio. December 10, 2025. https://gribio.com/gri-bio-announces-positive-topline-data-from-its-phase-2a-study-in-idiopathic-pulmonary-fibrosis-ipf/

2. GRI Bio Announces Additional Positive Data from Phase 2a Study in Idiopathic Pulmonary Fibrosis, Strengthening Clinical Proof-of-Concept for GRI-0621. News release. GRI Bio. January 8, 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/