GRI Bio today announced the publication of an article that reviews data in both experimental models and in humans that suggest a key role of type 1 invariant NKT (iNKT) cell activation in the progression of inflammatory cascades leading to recruitment of neutrophils and activation of the inflammasome, macrophages, fibroblasts, and, ultimately, fibrosis.
In several murine models of chronic inflammation and fibrosis, as well as in humans, it has been shown that iNKT cells are selectively activated in the disease setting
Data supports GRI Bio’s leading NKT regulation technology which targets the inflammatory cascade earlier to modulate disease progression
Company advancing toward launch of Phase 2a biomarker study evaluating GRI-0621 for the treatment of IPF before year end 2023
LA JOLLA, CA, Oct. 05, 2023 (GLOBE NEWSWIRE) -- 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 publication of an article that reviews data in both experimental models and in humans that suggest a key role of type 1 invariant NKT (iNKT) cell activation in the progression of inflammatory cascades leading to recruitment of neutrophils and activation of the inflammasome, macrophages, fibroblasts, and, ultimately, fibrosis. The manuscript titled, “Type 1 invariant natural killer T cells in chronic inflammation and tissue fibrosis,” has been published in Frontiers in Immunology.1
Natural killer T (NKT) cells are innate-like T cells that share properties of both NK cells and T lymphocytes. NKT cells are pre-loaded with cytokine message and respond quickly in immune responses, but also help to maintain and propagate chronic long term immune responses. They interact with and influence the activity of other cell types and are a functional link between the innate and adaptive immune systems. iNKT are pro-inflammatory effector T cells that accumulate in many models of chronic fibrotic diseases such as idiopathic pulmonary fibrosis (IPF), lupus nephritis and NASH. Type 2 NKT cells are anti-inflammatory regulatory T cells that can reset unwanted immune responses that contribute to many autoimmune disorders such as systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. GRI has a robust portfolio of patented drug candidates that regulate NKT cells.
“There remains a significant unmet need with no existing therapeutic solutions that halt disease progression of fibrotic diseases such as IPF and NASH. This review provides valuable insight and is a step forward in attaining a better understanding of the cellular and molecular mechanisms involved in progressive fibrotic disease. I am encouraged by the emerging experimental evidence that iNKT cells play an important role in chronic inflammation and fibrosis. I look forward to the continued advancements toward a potential therapeutic and ultimately address this significant unmet need for a solution for chronic inflammation and tissue fibrosis,” commented Dr. Cormac McCarthy, Associate Professor of Medicine at University College Dublin, School of Medicine. and Consultant Respiratory Physician at St. Vincent’s University Hospital.
“We continue to establish a growing body of data highlighting the positive effect of targeting the immune response earlier in the inflammatory cascade to interrupt disease progression. Our belief in the potential of our NKT platform technology continues to build and we remain focused on leveraging its potential to develop novel biomarkers and therapeutic targets that differentiate stages of fibrosis progression,” commented Marc Hertz, PhD, Chief Executive Officer of GRI Bio. “Supported by this compelling emerging data in experimental models of fibrosis, our team continues to make solid progress in the advancement of our lead programs, GRI-0621 and GRI-0803. We believe GRI is poised to interrupt disease progression and importantly, provide benefit to patients.”
Emerging evidence suggests that iNKT-associated mechanisms contribute to type 1, type 2 and type 3 immune pathways mediating tissue fibrosis, including IPF. IPF is a rare chronic progressive pulmonary disease with abnormal scarring of the lung blocking the movement of oxygen into the bloodstream. Currently, no therapeutic solution exists that halt disease progression of IPF and a better understanding of the cellular and molecular mechanisms involved in progressive fibrotic disease is necessary for the development of new therapeutic interventions.
Key Highlights
- iNKT cells are involved in the regulation of all three, type 1, type 2 and type 3 cytokine associated fibrotic pathways. The cross regulation of iNKT cell subsets as well as mechanisms that dictate whether type 1, type 2, or type 3 immunity predominates during the progression of lung fibrosis in IPF are not clear. However, based on data from disease models, inhibition of iNKT cells, including NKT1, NKT2 and NKT17 subsets, is likely to inhibit type 1, 2 and 3 key cytokine pathways driving fibrosis in IPF.
- Consistent with the experimental data, iNKT cells are chronically activated and secrete significantly higher levels of proinflammatory cytokines in NASH, severe alcoholic hepatitis, lupus nephritis and accumulate in IPF patients in comparison to healthy volunteers.
- Neutrophil accumulation into fibrotic liver tissue is dependent on the activation of iNKT cells. This is due to the inhibition of the upregulation of several cytokines and chemokines, including MIP-1, MIP-2, IL-6, and osteopontin that are involved in the neutrophil infiltration into tissues following injury.
- Targeting an immune pathway that can facilitate a re-balancing of downstream pathways, and restoring immune homeostasis, may be crucial for an effective treatment strategy for fibrosis. As covered in this published NKT review manuscript, the blocking of an earlier upstream pathway, such as iNKT cell activation, may dampen all three key cytokine-associated pathways and ultimately may lead to the development of novel therapeutic strategies in IPF.
GRI Bio’s lead program, GRI-0621 is a small molecule RAR-βɣ dual agonist that inhibits the activity of human type 1, iNKT cells. In preliminary trials to date2 and previous trials with the oral formulation, GRI-0621 has been shown to improve fibrosis in multiple disease models and improve LFTs and other markers of inflammation and injury in patients. The Company remains on track to launch its Phase 2a biomarker study evaluating GRI-0621 for the treatment of IPF before year end 2023.
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.
Forward Looking Statements
This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “aim,” “should,” “will,” “would,” or the negative of these words or other similar expressions. These forward-looking statements are based on the Company’s current beliefs and expectations. Forward-looking statements include, but are not limited to, statements regarding: the Company’s expectations with respect to development and commercialization of the Company’s product candidates, the initiation or completion of clinical trials, the potential benefits and impact of the Company’s product candidates and the related timing of regulatory approvals, if any, evaluations and judgements regarding the Company’s intellectual property position, the ability of the Company to achieve the milestones presented and the timing of such milestones, any implication that the results or preliminary results of earlier or prior clinical trials will be representative or indicative of future clinical trials, estimates regarding the funding necessary to fund the Company’s planned operations and any estimate or implication as to potential market size or potential revenue. Actual results may differ from the forward-looking statements expressed by the Company in this press release and consequently, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including, without limitation: (1) the inability to maintain the listing of the Company’s common stock on Nasdaq; (2) changes in applicable laws or regulations; (3) the inability of the Company to raise financing in the future; (4) the success, cost and timing of the Company’s product development activities; (5) the inability of the Company to obtain and maintain regulatory clearance or approval for their products, and any related restrictions and limitations of any cleared or approved product; (6) the inability of the Company to identify, in-license or acquire additional technology; (7) the inability of the Company to compete with other companies currently marketing or engaged in the development of products and services that the Company is currently developing; (8) the size and growth potential of the markets for the Company’s products and services, and its ability to serve those markets, either alone or in partnership with others; (9) inaccuracy in the Company’s estimates regarding expenses, future revenue, capital requirements and needs for and the ability to obtain additional financing; (10) the Company’s ability to protect and enforce its intellectual property portfolio; and (10) other risks and uncertainties indicated from time to time in the Company’s filings with the U.S. Securities and Exchange Commission (the “SEC”), including the risks and uncertainties described in the “Risk Factors” section of the Company’s most recent Annual Report on Form 10-K filed with the SEC on and Quarterly Report on Form 10-Q filed with the SEC on May 15, 2023 and subsequently filed reports. Forward-looking statements contained in this announcement are made as of this date, and the Company undertakes no duty to update such information except as required under applicable law. This press release also contains estimates and other statistical data made by independent parties and by the Company relating to market size and growth and other data about its industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates.
Investor Contact:
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1 Front. Immunol., 25 September 2023, Sec. T Cell Biology, Volume 14 - 2023 | https://doi.org/10.3389/fimmu.2023.1260503
2 I. Maricic et al., Differential Activation of Hepatic Invariant NKT Cell Subsets Plays a Key Role in Progression of Nonalcoholic Steatohepatitis. J Immunol201, 3017-3035 (2018), Tazoral™ for the Treatment of Moderate to Very Severe Plaque Psoriasis Briefing Document, Allergan
(https://wayback.archive-it.org/7993/20170405104812/https://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4062B1_01_Allergan-Background.pdf)
