GRI Bio Shares Promising Preclinical Data on NKT Cell Modulators for SLE Treatment

GRI Bio, Inc., a biotechnology firm listed on NASDAQ, recently showcased promising preclinical data regarding their novel NKT cell modulators for treating inflammatory, fibrotic, and autoimmune diseases. Vipin Kumar Chaturvedi, PhD, the Chief Scientific Officer of GRI Bio, presented the data at the 14th International Congress on Autoimmunity in Ljubljana, Slovenia, covering their work on type 2 NKT activating molecules, specifically GRI-0803 and GRI-0124.

GRI-0803, the company's second developmental asset, is a pioneering activator of human type 2 NKT cells. This activation inhibits type 1 invariant NKT (iNKT) cells through a dendritic cell-mediated process. In preclinical studies, GRI-0803 and GRI-0124 were shown to inhibit iNKT cells in both human and murine models. Oral administration of these molecules was found to inhibit lupus nephritis and significantly enhance overall survival rates. The company is advancing GRI-0803 specifically for systemic lupus erythematosus (SLE), an autoimmune disease where the immune system attacks its own tissues and organs.

Dr. Chaturvedi highlighted the significant unmet need for safe and effective SLE treatments, as current therapies are mainly immunosuppressive. He emphasized that the preclinical data for GRI-0803 and GRI-0124 suggest these molecules could intervene earlier in the inflammatory process, potentially halting disease progression. The company aims to validate bioanalytical methods, complete cGMP manufacturing, and finalize toxicology studies to file an IND for GRI-0803 by the third quarter of 2024, with topline data expected by the fourth quarter.

Key observations from the preclinical studies revealed that iNKT cells, which accumulate in SLE patients and NZBWF1 mice, exhibit an activated phenotype and show chronic activation. Type 2 NKT cells, which accumulate in the kidneys of NZBWF1 mice, remain responsive to stimulation and inhibit iNKT cell activity.

In detailed findings, the once-weekly administration of GRI-0124 demonstrated multiple beneficial effects. It inhibited pro-inflammatory cytokines and signaling pathways, decreased pDC accumulation and MHC class II expression, and inhibited various immune cells, including CD4+, CD8+ T cells, and B cells, while showing a favorable balance between T1B and T2B cells. Additionally, GRI-0124 reduced renal cellular infiltration and fibrosis, inhibited proteinuria, and improved overall survival rates.

GRI-0803, which shares a chemical backbone with type 2 GRI-0124 and has a molecular weight of less than 400g/mol, showed favorable solubility and excellent bioavailability upon oral administration. It has demonstrated a favorable pharmacokinetic profile with no cardiovascular toxicology issues, genotoxicity, or adverse interactions within the CYP450 pathway.

GRI Bio is a clinical-stage biopharmaceutical company pioneering treatments for inflammatory, fibrotic, and autoimmune diseases by targeting NKT cells, crucial regulators in the inflammatory cascade. The company's lead program, GRI-0621, is an inhibitor of iNKT cell activity, being developed as an oral treatment for idiopathic pulmonary fibrosis. Additionally, the company is working on a lineup of novel type 2 NKT agonists for systemic lupus erythematosus and maintains a library of over 500 proprietary compounds to support its growing pipeline.