Data presented at The Autoimmunity Conference hosted by the Federation of American Societies for Experimental Biology (FASEB)

GRI-0803 in development with an initial focus on the treatment of systemic lupus erythematosus (SLE)

Company expects to commence Phase 1a/b SLE study in 1H 2024 with topline results expected 2H 2024

LA JOLLA, CA, USA I August 07, 2023 I GRI Bio, Inc. (NASDAQ: GRI) (“GRI Bio” or the “Company”), a biotechnology company advancing an innovative pipeline of Natural Killer T (“NKT”) cell modulators for the treatment of inflammatory, fibrotic and autoimmune diseases, today announced the presentation of preclinical data from its GRI-0803 development program at The Autoimmunity Conference hosted by FASEB held July 30-August 3, 2023 in Southbridge, MA.

GRI-0803 is the Company’s novel activator of human type 2 NKT cells in development for the treatment of autoimmune disorders, with an initial focus on SLE, the most common form of lupus, is an autoimmune disease in which the immune system attacks its own tissue and organs.

As part of the conference, Albert Agro, PhD, Chief Medical Officer of GRI Bio presented preclinical data from its GRI-0803 asset in development in an abstract titled, “Type 2 NKT cells directed immune regulatory mechanism in lupus nephritis,” in the Novel Translational and Clinical Treatments for Autoimmune Disease session held on August 3, 2023.

Dr. Agro commented, “We remain highly encouraged by the animal model data that we observed in connection with GRI-0124 and the second-generation type 2 NKT cell agonist, GRI-0803. Oral administration of type 2 NKT cell agonists have been observed to inhibit animal models of lupus nephritis, proteinuria, and to significantly improve overall survival in these animal models.”

“Our growing body of data gives us further confidence in GRI Bio’s approach to play an important role in the treatment of SLE, especially given there have been only two drugs approved for this indication in more than 50 years. We are excited by GRI-0803’s potential and are working in earnest to complete our IND-enabling studies to position us to commence our Phase 1a/b study early next year,” added Dr. Agro.

Natural killer T (NKT) cells recognize lipid antigens presented by CD1d molecules and can be categorized into two subsets: type 1 or invariant (iNKT) and type 2 NKT cells. Type 2 NKT cells recognize lipids such as sulfatide or lysophosphatidylcholine (LPC), and their activation results in cross-regulation of iNKT cells, tolerization of DC resulting in a net positive effect during inflammatory diseases. iNKT cells play a pathogenic role in a murine model of lupus in (NZB x NZW) F1 or BWF1 mice and are also activated in lupus patients as demonstrated by the increased release of the pro-inflammatory cytokine IFNɣ. Interestingly, anti-glycosphingolipid antibody responses have been found in lupus patients and sulfatide is enriched in kidney glomeruli.

The Company has investigated the role of type 2 NKT cells in the spontaneous development of lupus in BWF1 mice. Results from the studies found that both iNKT and type 2 NKT cells accumulate in kidney tissues with progression of disease in BWF1 mice. Type 2 NKT cell activation leads to a significant inhibition of nephritis in these mice. A clinically relevant structural analog of LPC, GRI-0124 also binds to CD1d, activates type 2 NKT cells and upon oral administration induces inhibition of proteinuria, anti-dsDNA antibodies as well as infiltration of CD4+/CD8+ T cells and B cells into kidney of BWF1 mice. These studies suggest a key role for a type 2 NKT cell-based immune regulatory mechanism in the control of lupus.

Based on the data demonstrated to date, GRI Bio plans to evaluate GRI-0803 in a hybrid designed Phase 1 program. Healthy volunteers (SAD trial) and patients with SLE (MAD trial) will be assessed to examine the safety and tolerability of GRI-0803. A number of biomarkers will be evaluated in the MAD to validate the role of NKT 2 cell activation in SLE. The Company is working to complete IND-enabling studies for GRI-0803 and file an IND in 2024.

About GRI Bio, Inc.

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 I invariant NKT (“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.