GRI Bio Showcases GRI-0621’s Potential to Reduce Inflammation, Type 1 Cytokines & Reduce Hepatic Fibrosis in Idiopathic Pulmonary Fibrosis

GRI Bio, Inc. recently announced the presentation of positive preclinical data demonstrating its lead program GRI-0621 reduces important inflammatory and fibrotic drivers in Idiopathic Pulmonary Fibrosis (IPF).

The data were presented as part of an invited talk titled, A New Approach to Inflammatory Diseases, delivered by Marc Hertz PhD, Chief Executive Officer of GRI Bio, at the 8th Annual Antifibrotic Drug Development (AFDD) Summit, held November 19-21, 2024, in Boston, MA.

“We were pleased to participate at this prestigious event and engage with thought leaders in the field and present our novel approach for the treatment of inflammatory diseases. There remains a significant unmet need for therapeutic solutions that halt disease progression of fibrotic diseases such as IPF. Based on the growing body of positive data demonstrated by our lead program GRI-0621, we believe we have a validated and derisked clinical approach to address that need,” commented Marc Hertz, PhD, Chief Executive Officer of GRI Bio. “We believe GRI-0621 has the potential to provide meaningful benefit to IPF patients and we look forward to advancing it development and realizing its full value.”

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-β

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 (BAL) fluid from IPF patients and healthy controls to characterize NKT cells. A bleomycin (3.0 IU/Kg via the intratracheal route) 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-α1, osteopontin and TGF-β. There was an increase in IFN-_γ producing CD45+CD3+CD56+ NKT cells in IPF patients compared to controls. In a second cohort, we confirmed the iNKT phenotype using an anti-Vα24-Jα18 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-βɣ 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. For more information about the Phase 2a study, please visit clinicaltrials.gov and reference identifier NCT06331624.

GRI Bio is a clinical-stage biopharmaceutical company focused on fundamentally changing the way inflammatory, fibrotic and autoimmune diseases are treated. GRI Bio’s therapies are designed to target the activity of NKT cells, which are key regulators earlier in the inflammatory cascade, to interrupt disease progression and restore the immune system to homeostasis. NKT cells are innate-like T cells that share properties of both NK and T cells and are a functional link between the innate and adaptive immune responses. Type 1 invariant (iNKT) cells play a critical role in propagating the injury, inflammatory response, and fibrosis observed in inflammatory and fibrotic indications. GRI Bio’s lead program, GRI-0621, is an inhibitor of iNKT cell activity and is being developed as a novel oral therapeutic for the treatment of idiopathic pulmonary fibrosis, a serious disease with significant unmet need. The company is also developing a pipeline of novel type 2 NKT agonists for the treatment of systemic lupus erythematosus. Additionally, with a library of over 500 proprietary compounds, GRI Bio has the ability to fuel a growing pipeline.