GRI Bio presents translational data on NKT cells in patients with IPF

GRI Bio announced the presentation of translational data at the 2023 Pittsburgh-Ireland International Lung Conference: Precision Medicine in Lung Diseases: From Cellular Mechanisms to Clinical Phenotypes held October 16-17, 2023 at the RCSI University of Medicine and Health Sciences in Dublin, Ireland. The abstract titled “Altered NKT cell populations in the airways of patients with IPF,” was presented in a poster presentation by collaborator Emily Calamita of Dr. Adam Byrne’s laboratory. IPF is a rare chronic progressive pulmonary disease with abnormal scarring of the lung blocking the movement of oxygen into the bloodstream. Natural killer T cells are a subset of innate-like T lymphocytes that recognize lipid antigens, by expressing the T-cell receptor Valpha24-Jalpha18 chain. Upon activation, NKT cells produce numerous cytokines, including those that have been shown to drive IPF pathogenesis. In animal models of lung fibrosis, NKT cells have been shown to drive IPF pathology. However, their role in human IPF remains unknown. For the translational study, surface and intracellular flow cytometry of cells isolated from bronchoalveolar lavage and blood of healthy donors and IPF patients was conducted to characterize their NKT cell compartment. Key Findings: In the BAL of IPF patients, a significant increase in the number of NKT cells was observed in comparison to healthy controls. Numbers of NKT cells correlated positively with the number of airway macrophages in IPF BAL. Increased expression of NKT-IFNgamma was also observed in the BAL of IPF patients relative to controls. The number of NKT cells positively correlated with the number of airway macrophages in IPF patients. However, the correlation with lung function parameters did not reach significance in this small study. GRI Bio’s lead program, GRI-0621 is a small molecule RAR-beta dual agonist that inhibits the activity of human type 1, iNKT cells. In preliminary trials to date1 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. GRI is developing and repurposing GRI-0621 as a once-daily oral capsule for the treatment of IPF with the potential to expand into additional fibrotic indications. The Company plans to leverage the 505(b)(2) regulatory pathway and to launch a Phase 2a biomarker study evaluating GRI-0621 for the treatment of IPF. The Company is on track to launch its Phase 2a biomarker study of GRI-0621 before year-end.