GRI Bio presents preclinical data on GRI-0621 in IPF

GRI Bio (GRI) announced the presentation of preclinical data demonstrating its lead program GRI-0621 reduces important inflammatory and fibrotic drivers in Idiopathic Pulmonary Fibrosis. The data were presented as part of an invited talk titled, “A New Approach to Inflammatory Diseases,” delivered by Marc Hertz PhD, CEO of GRI Bio, at the 8th Annual Antifibrotic Drug Development Summit, held November 19-21, 2024, in Boston, MA. Key Highlights: Enhanced iNKT activity correlates with progression of fibrosis in MASH patients and key proinflammatory genes in BAL from IPF patients; iNKT cells are activated and accumulate in liver and lung in experimental fibrosis models; iNKT promote Type 1, Type 2 and Type 3 immune pathways involved in fibrosis; iNKT-deficient mice have reduced inflammatory damage and fibrosis; Daily oral administration of GRI-0621 in experimental animals; Inhibits key pro-inflammatory cytokines and inflammation; Decreases accumulation of neutrophils and activation of pro-fibrotic fibroblasts; Inhibits key fibrogenic cytokines including TGF-beta; Additionally, the Company presented a poster titled, “Involvement of Type 1 Invariant Natural Killer T Cells in Driving Lung Fibrosis,” outlining flow cytometry and quantitative PCR analysis in bronchoalveolar lavage fluid from IPF patients and healthy controls to characterize NKT cells. A bleomycin model was used with or without daily administration of nintedanib or a small molecule selective inhibitor of iNKT activity, GRI-0621, during the fibrotic phase to study the role of iNKT cells in pulmonary fibrosis in a treatment protocol. Results highlighted in the poster demonstrated that IPF patients had increased expression of pro-fibrotic molecules in BAL, including Collagen 1-alpha1, osteopontin and TGF-beta. There was an increase in IFN-gamma producing CD45+CD3+CD56+ NKT cells in IPF patients compared to controls. In a second cohort, we confirmed the iNKT phenotype using an anti-Valpha24-Jalpha18 TCR antibody. In the bleomycin model, GRI-0621 inhibition of iNKT cells improved a majority of inflammatory, fibrotic, and pathological features, including a reduction in lung injury, myofibroblast activity, collagen deposition, and fibrosis. GRI Bio’s lead program, GRI-0621, is a small molecule RAR-beta dual agonist that inhibits the activity of human iNKT cells. In preliminary trials to date and previous trials with the oral formulation, GRI-0621 has been shown to improve fibrosis in multiple disease models and improve liver function tests and other markers of inflammation and injury in patients. The Company is currently advancing the development of GRI-0621 in a Phase 2a, randomized, double-blind, multi-center, placebo-controlled, parallel-design, 2-arm study for the treatment of IPF. Interim data from the Phase 2a biomarker study is expected in the first quarter of 2025 and topline results are expected in the second quarter of 2025