GRI Bio Reports Promising Preclinical Results for GRI-0621 in Treating IPF

Recent data indicate that Natural Killer T (NKT) cells are activated in the airways of Idiopathic Pulmonary Fibrosis (IPF) patients, and inhibiting iNKT cell activity can mitigate bleomycin-induced pulmonary fibrosis. GRI Bio, Inc., a biotechnology company focusing on NKT cell modulators to treat inflammatory, fibrotic, and autoimmune diseases, has shared promising preclinical data on its lead program, GRI-0621.

Presented at the 22nd International Colloquium on Lung and Airway Fibrosis, the study highlighted the reduction of significant inflammatory and fibrotic drivers in IPF. Vipin Kumar Chaturvedi, PhD, Chief Scientific Officer of GRI Bio, discussed the analysis of bronchoalveolar lavage (BAL) fluid from IPF patients and the effects of GRI-0621 in a pulmonary fibrosis treatment model.

Marc Hertz, PhD, CEO of GRI Bio, expressed confidence in their therapeutic targets, noting that the preclinical data provides valuable insights into the inhibition of iNKT cell activity in advanced stages of a preclinical IPF model. The company believes GRI-0621 could substantially benefit IPF patients and is focused on advancing towards interim data and topline results from their Phase 2a biomarker study in the coming quarters.

Key findings from the study include increased expression of pro-fibrotic factors like Collagen 1-α1, osteopontin, and TGF-β in IPF patients, detected through qPCR in whole BAL pellets. Researchers observed a rise in IFN-γ producing NKT cells in IPF patients compared to controls and confirmed the iNKT cell phenotype in a second cohort using an antibody against Vα24-Jα18 of the iNKT TCR. GRI-0621 treatment, administered during the fibrotic phase of the bleomycin model, improved numerous inflammatory, fibrotic, and pathological features, including reductions in lung injury, myofibroblast activity, collagen deposition, and fibrosis.

IPF is a rare, chronic, and progressive lung disease characterized by abnormal lung scarring, which impedes oxygen transfer to the bloodstream. This leads to breathlessness, significant quality of life decline, and an average untreated survival of 3.5 years post-diagnosis. Current IPF treatments are limited, with only two approved drugs that have notable side effects, limited compliance, and no impact on survival rates.

GRI Bio is actively advancing GRI-0621, a small molecule RAR-βɣ dual agonist candidate that inhibits human iNKT cell activity, through a Phase 2a, randomized, double-blind, multi-center, placebo-controlled, parallel-design, 2-arm study for treating IPF. Interim data from this study is anticipated in the fourth quarter of 2024, with topline results expected in the first quarter of 2025.

GRI Bio is dedicated to fundamentally changing the treatment approach for inflammatory, fibrotic, and autoimmune diseases. Their therapies target NKT cell activity, which are pivotal in the early stages of the inflammatory cascade, to halt disease progression and restore immune system balance. NKT cells, which share characteristics with both NK and T cells, act as a functional link between innate and adaptive immune responses. Type 1 invariant (iNKT) cells are crucial in promoting injury, inflammation, and fibrosis observed in these conditions. GRI Bio's lead program, GRI-0621, is being developed as a novel oral therapeutic for IPF, addressing a significant unmet medical need. The company is also progressing with a pipeline of novel type 2 NKT agonists for treating systemic lupus erythematosus, supported by a proprietary compound library of over 500 entries to fuel their expanding pipeline.