GRI Bio Presents Positive Pre-Clinical Data Demonstrating GRI-0621 Resolves Inflammation and Fibrosis in Bleomycin-Induced Fibrosis and Reiterates Promising Preliminary Phase 2a Clinical Results
- Preclinical data shows GRI-0621 performs as well or better than approved drug nintedanib
- Interim Phase 2a results demonstrate safety and tolerability with no hyperlipidemia
- Early biomarker results suggest anti-fibrotic effects
- Independent Data Monitoring Committee recommends study continuation with no safety concerns
- None.
Insights
GRI-0621 shows promising pre-clinical and early clinical data for IPF treatment with dual anti-inflammatory and anti-fibrotic effects.
The pre-clinical data presented by GRI Bio at the ATS conference provides compelling evidence for GRI-0621's mechanism of action in pulmonary fibrosis. The compound targets iNKT cells after the inflammatory phase has completed, which represents a distinct approach compared to current therapies. What's particularly noteworthy is that GRI-0621 demonstrated effectiveness comparable or superior to nintedanib, one of only two FDA-approved medications for IPF.
The bleomycin-induced fibrosis model is the gold standard for pre-clinical evaluation of anti-fibrotic compounds, and GRI-0621 showed significant inhibition of several critical disease drivers: lung injury markers, fibroblast activation, myofibroblast differentiation, and extracellular matrix deposition. These are all essential targets in managing pulmonary fibrosis progression.
The interim clinical data, while limited to 2-week safety results in 12 patients, addresses a critical concern for this drug class – hyperlipidemia wasn't observed, which differentiates it from other RAR agonists. Moreover, the early biomarker data showing changes in PRO-C3 levels is particularly encouraging. PRO-C3 is a validated biomarker of active collagen formation and fibrotic activity, and its reduction suggests the compound is engaging its intended biological targets in patients.
IPF remains a devastating disease with median survival of just 3-5 years post-diagnosis. Current treatments only slow progression without addressing underlying pathology. GRI-0621's dual anti-inflammatory and anti-fibrotic properties could potentially offer more comprehensive disease management if confirmed in larger studies. The upcoming 6-week interim analysis in Q2 2025 and final results in Q3 2025 will be critical in determining whether these promising signals translate to clinically meaningful outcomes.
Data presented at the 2025 American Thoracic Society (ATS) International Conference
Pre-clinical and interim clinical results underscore GRI-0621’s potential to have both anti-inflammatory and anti-fibrotic effects in pulmonary fibrosis
Results from 6-week interim analysis (n=24) in ongoing Phase 2a study of GRI-0621 for the treatment of Idiopathic Pulmonary Fibrosis (IPF) anticipated in Q2 2025
LA JOLLA, CA, May 22, 2025 (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 presentation of positive preclinical data demonstrating its lead program GRI-0621 has anti-inflammatory and anti-fibrotic effects in pulmonary fibrosis.
The data was presented by Marc Hertz, PhD, Chief Executive Officer of GRI Bio in the poster titled, “Inactivation of iNKT Cells After the Inflammatory Phase Leads to Significant Inhibition of Fibroblast Activation and Fibrosis in a Model of Pulmonary Fibrosis,” as part of the D21 - IMMUNOLOGICAL INSIGHTS IN LUNG INFLAMMATION AND REPAIR session at the 2025 ATS International Conference held on Wednesday, May 21, 2025.
“We continue believe GRI-0621 is a promising potential treatment option for IPF, an indication where there remains significant unmet need. Our growing body of pre-clinical results continue to bolster our understanding of the role of iNKT cell activity in driving pulmonary fibrosis and further support our ongoing Phase 2a study examining the safety and tolerability of GRI-0621 and its effect on various biomarkers in IPF patients. We remain encouraged by the progress made in our Phase 2a biomarker study and look forward to reporting additional data this year,” commented Marc Hertz, PhD, Chief Executive Officer of GRI Bio.
The presented data highlights results from biochemical, qPCR and immunohistochemistry analyses, used to investigate whether iNKT cell inactivation during the fibrotic phase resolves lung injury, fibroblast activation, and fibrosis in the murine bleomycin model of pulmonary fibrosis.
Key Highlights
- In a therapeutic regimen of the bleomycin-induced fibrosis model, orally administered GRI-0621 after completion of the inflammatory phase (Day 7), significantly inhibits lung injury and several important fibrotic cellular and molecular drivers of lung disease, including fibroblast activation and fibrosis.
- GRI-0621 demonstrated to impact key innate and adaptive cell activity, cytokine production, myofibroblast activation, and ECM deposition and fibrosis.
- GRI-0621 inhibition of iNKT cell activity is therapeutic in treatment models of pulmonary fibrosis and performs as well or better than the approved drug nintedanib.
GRI Bio’s lead program, GRI-0621, is a small molecule RAR-βɣ dual agonist that inhibits the activity of human iNKT cells. GRI-0621 is currently being assessed in a 12-week, double-blind, randomized, placebo-controlled study in patients with IPF to assess the safety and tolerability of GRI-0621. In addition, the effect of GRI-0621 on a number of biomarkers both from the blood and bronchoalveolar lavage (BAL) will be evaluated. These include several biomarkers associated with disease progression, NKT cell and other immune cell numbers and activity, differential gene expression, as well as pulmonary function tests.
As previously announced, the pre-planned interim analysis for 2-week safety results from the ongoing Phase 2a biomarker study demonstrated GRI-0621 (4.5mg orally once daily) to be safe and well-tolerated in the first 12 patients evaluated per protocol. Hyperlipidemia, as assessed by LDL, HDL and triglyceride (TG) levels, was not seen in the 12 patients assessed at the 2-week visit. There were no meaningful changes in HDL, LDL or TG levels in patients receiving GRI-0621. The interim analysis committee recommended the study should continue as planned. The interim results show that GRI-0621’s receptor selectivity is consistent with the toxicity profile observed in earlier studies evaluating oral tazarotene in over 1,700 patients treated for up to 52 weeks.
Additionally, interim biomarker results from the first 12 subjects at 2 weeks were reviewed by the IDMC and determined that the change from baseline in PRO-C3 of GRI-0621-treated patients compared to placebo patients is suggestive of anti-fibrotic effect. Based on the available interim data reviewed, the IDMC has recommended the Phase 2a study evaluating GRI-0621 to continue as planned as there are no safety concerns seen to date.
Topline results from the Phase 2a biomarker study are expected in the third quarter of 2025.
For more information about the Phase 2a study, please visit clinicaltrials.gov and reference identifier NCT06331624.
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 Natural Killer T (“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 diverse NKT (“dNKT”) 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
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Investor Contact:
JTC Team, LLC
Jenene Thomas
(908) 824-0775
GRI@jtcir.com
FAQ
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