Biotechnology Company Announces Preclinical Data: Type 2 NKT Activating Molecules
GRI Bio Presents Positive Preclinical Data from Pipeline of NKT Cell Modulators in Development for the Treatment of Systemic Lupus Erythematosus (SLE).
As an investor it's important to stay updated with major news. Get real-time stock market alerts, news, and research by creating an account here.
GRI Bio, Inc. (NASDAQ: GRI) (“GRI Bio,” “we,” “our,” 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 encouraging preclinical data at the 14th International Congress on Autoimmunity held May 17-20, 2024, in Ljubljana, Slovenia (the Congress). Dr. Vipin Kumar Chaturvedi, Chief Scientific Officer of GRI Bio, unveiled the promising results from the Company’s preclinical studies on type 2 NKT activating molecules, GRI-0803 and GRI-0124.
The Innovative Approach of GRI-0803 and GRI-0124
GRI Bio’s second asset in development, GRI-0803, is a novel activator of human type 2 NKT cells. Activation of type 2 NKT cells leads to a dendritic cell-mediated inhibition of type 1 invariant NKT (iNKT) cells. In the Company’s preclinical studies, these type 2 NKT activating molecules, specifically GRI-0803 and GRI-0124, were observed to inhibit both murine and human iNKT cells effectively. Oral administration of these molecules showed a significant inhibitory effect on lupus nephritis and substantially improved overall survival in preclinical models. The Company is currently advancing the development of GRI-0803 for the treatment of systemic lupus erythematosus (SLE), an autoimmune disease wherein the immune system attacks its own tissues and organs.
Dr. Chaturvedi stated, “There remains a significant unmet need for safe and effective treatment options for SLE as current treatments are limited, consisting primarily of immunosuppressive therapies. Based on the data demonstrated by GRI-0803 and GRI-0124 to date, we believe these innovative small molecules leveraging NKT science have the potential to target earlier in the inflammatory cascade to interrupt disease progression. We remain encouraged by GRI-0803’s potential and are working in earnest to validate bioanalytical methods, complete cGMP manufacturing, and complete toxicology studies in order to file our IND for GRI-0803 in the second half of 2024.”
Key Highlights from GRI Preclinical Studies
The following key highlights were observed during the preclinical studies conducted by GRI Bio:
Accumulation and Activation of iNKT Cells:
Data demonstrate that iNKT cells accumulate in SLE patients and in NZBWF1 mice, exhibiting an activated phenotype. Their hyporesponsiveness to in vitro stimulation suggests chronic activation.
Type 2 NKT Cells in NZBWF1 Mice:
Type 2 NKT cells accumulate in NZBWF1 kidneys and remain responsive to in vitro restimulation.
Activation of type 2 NKT cells in NZBWF1 mice inhibits iNKT cell activity.
Once-Weekly Administration of GRI-0124:
Inhibited pro-inflammatory cytokines and signaling pathways in NZBWF1 mice.
Decreased plasmacytoid dendritic cell (pDC) accumulation and Major Histocompatibility Complex (MHC) class II expression.
Inhibited CD4+, CD8+ T cells, and B cells, with an increase in type 1 B cells (T1B) and a decrease in type 2 B cells (T2B).
Reduced renal cellular infiltration and fibrosis.
Inhibited proteinuria, anti-dsDNA immunoglobulin, and improved overall survival and proteinuria-free survival.
Advancements of GRI-0803:
GRI-0803 exhibits a chemistry backbone based on type 2 GRI-0124.
It has a molecular weight of less than 400 g/mol.
It boasts a favorable solubility profile and excellent bioavailability.
Its pharmacokinetic (PK) profile supports once-daily (q.d.) oral administration.
No cardiovascular toxicology issues have been observed, no genotoxicity, and no activation or inhibition within the cytochrome P450 (CYP450) pathway.
To date, no toxicology concerns have emerged.
Integrating NKT Cell Modulators into SLE Treatment
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the immune system attacking the body's tissues and organs. Traditional treatments for SLE involve immunosuppressive therapies, which often come with significant side effects and are not always effective in halting disease progression. GRI Bio's approach, targeting NKT cells, offers a novel mechanism that could potentially address the root cause of the disease rather than merely alleviating symptoms. NKT cells play a crucial role in the regulation of immune responses. Type 1 invariant NKT (iNKT) cells are known to promote inflammation, which is a critical factor in the pathogenesis of SLE. By contrast, type 2 NKT cells, when activated, can inhibit the activity of iNKT cells. This inhibition reduces the inflammatory response and has the potential to halt disease progression.
GRI-0803 and GRI-0124 are designed to activate type 2 NKT cells, thus offering a targeted approach to modulate the immune response in SLE. The preclinical data showing the accumulation of type 2 NKT cells in the kidneys of NZBWF1 mice and their responsiveness to stimulation underscores the therapeutic potential of these molecules. The success of GRI-0803 and GRI-0124 in preclinical studies paves the way for clinical trials. The upcoming steps include the validation of bioanalytical methods, completion of current Good Manufacturing Practice (cGMP) manufacturing, and comprehensive toxicology studies. Filing an Investigational New Drug (IND) application in the second half of 2024 will be a critical milestone for GRI Bio. If the clinical trials mirror the preclinical results, GRI-0803 and GRI-0124 could revolutionize the treatment landscape for SLE. These molecules could provide a safer, more effective alternative to existing therapies, addressing the unmet needs of patients who suffer from this debilitating disease.
The presentation of positive preclinical data by GRI Bio marks a significant step forward in the development of innovative treatments for systemic lupus erythematosus. The potential of GRI-0803 and GRI-0124 to modulate NKT cells and inhibit the inflammatory cascade represents a promising new direction in autoimmune disease therapy. With further validation and successful clinical trials, these molecules could offer hope to millions of patients worldwide suffering from SLE.
Disclaimer: The information provided in this article is based on preclinical data and ongoing research by GRI Bio, Inc. The efficacy and safety of GRI-0803 and GRI-0124 in humans have not yet been established, and they are currently not approved for the treatment of any condition. The forward-looking statements made herein are subject to risks and uncertainties that could cause actual results to differ materially. Readers are advised to consult with healthcare professionals and rely on official medical guidance for the treatment of systemic lupus erythematosus.