LA JOLLA, Calif. — GRI Bio, Inc. (NASDAQ: GRI) (“GRI Bio” or the “Company”), a biotechnology company advancing an innovative pipeline of immune cell modulators for the treatment of inflammatory, fibrotic and autoimmune diseases, today announced positive topline data from the Phase 2a GRI-0621-IPF-02 clinical trial evaluating GRI-0621 for the treatment of Idiopathic Pulmonary Fibrosis (“IPF”). The study met its primary endpoint and secondary endpoints demonstrating that GRI-0621 was well tolerated over a 12-week treatment period, consistent with earlier studies evaluating over 1,700 subjects treated for up to a year. Subjects treated with GRI-0621 also displayed improvements in serum biomarkers of collagen turnover suggesting fibrosis resolution and induction of an alveolar basement membrane repair mechanism.
“Treatment of patients with IPF in the GRI-0621 Phase 2a trial was observed to be safe and well tolerated through the completion of the 12-week study,” said Toby Maher, MD, PhD, Professor of Clinical Medicine, Keck School of Medicine, USC Los Angeles. “Secondary endpoints related to the effect of GRI-0621 on biomarkers associated with disease progression provided evidence that GRI-0621 maintains a net anti-fibrotic effect compared to standard of care. Lastly, FVC improved in patients treated with GRI-0621, with more patients experiencing an increase at 12 weeks than with standard of care. We look forward to watching the clinical advancement of GRI-0621 as a potential treatment for patients with IPF.”
Study Met Its Primary Endpoint, Demonstrating a Safety Profile Differentiated From Existing Treatment Options
No safety or tolerability concerns were observed in the subjects enrolled at 12 weeks of treatment, with dry skin, dry lips, muscle and joint pain as the most common adverse events reported. There were no increases in cough (0% in the GRI-0621-treated arm compared to 25% in the placebo arm) or gastrointestinal disorders reported in the GRI-0621 arm compared to the placebo arm (diarrhea reported in 13% versus 33%, respectively). 80% of the subjects enrolled were taking background pirfenidone or nintedanib.
Study Met Secondary Endpoints Suggestive of Disease-Modifying Activity, Reversing Fibrosis and Inducing a Lung Repair Mechanism
Subjects treated with GRI-0621 also displayed improvements in serum biomarkers of collagen turnover, suggesting fibrosis resolution and induction of an alveolar basement membrane repair mechanism. PRO-C6, a biomarker of type VI collagen synthesis, was observed to decrease from baseline (-3%) in GRI-0621 treated subjects and increase (+12%) in subjects treated with placebo and standard of care. C6M, a biomarker of type VI collagen degradation, was observed to increase from baseline (+6%) in GRI-0621 treated subjects and decrease (-3%) in subjects treated with placebo and standard of care. The type VI collagen remodeling rate shifted from fibrogenic (+10%; continued worsening of fibrosis) in placebo-treated subjects to fibrolytic (-7%; resolution of fibrosis), suggestive of GRI-0621 inducing resolution of fibrosis in treated subjects compared to continued worsening of fibrosis in subjects treated with placebo and standard of care.
Destruction of the alveolar basement membrane is a hallmark of IPF, and type IV collagen synthesis, and repair of the basement membrane, is a crucial step in lung tissue repair. PRO-C4, a biomarker of type IV collagen synthesis, was observed to increase from baseline (+9%) in GRI-0621 treated subjects and decrease (-2%) in subjects treated with placebo and standard of care. C4Ma3, a biomarker of type IV collagen degradation, was observed to decrease in GRI-0621 treated subjects compared to subjects treated with placebo and standard of care (10% vs 24%, respectively). The type IV collagen remodeling rate shifted from fibrolytic (-16%; continued destruction of the basement membrane) in placebo-treated subjects to neutral (0%) in GRI-0621 treated subjects, suggestive of GRI-0621 inducing a lung tissue repair mechanism and repair of the alveolar basement membrane compared to placebo-treated subjects.
Interestingly, the alveolar basement membrane repair mechanism is supported by differential gene expression data of AT1 cell re-epithelialization of the basement membrane. GRI-0621 was observed to significantly reduce DLK1 (-6.46 LogFC; FDR 0.0003), a gene involved in lung epithelial AT2 cell fate plasticity and regeneration of alveolar AT1 cells (Sawhney, et al. (2025) Nat Commun 16, 8924; Li, et al. (2025) Resp Res 26 188), another critical step in alveolar basement membrane repair, compared to subjects treated with placebo and standard.
Reductions in neutrophil and macrophage activity (immune cell biomarkers upregulated in IPF and associated with disease progression) and downregulation of genes associated with fibrosis, disease progression and mortality were also observed in patients treated with GRI-0621 compared to placebo-treated subjects.
“The positive Phase 2a results represent an important milestone for our IPF program and a compelling early signal of GRI-0621’s disease-modifying potential. IPF remains one of the most devastating respiratory diseases, with limited treatment options and a significant need for therapies that can do more than slow decline and address the underlying biology of the disease,” commented Marc Hertz, PhD, Chief Executive Officer of GRI Bio. “In addition to a favorable safety and tolerability profile, GRI-0621 demonstrated meaningful improvement in biomarkers suggesting fibrosis resolution and repair of the alveolar basement membrane. These results reinforce our belief in GRI-0621’s differentiated mechanism and support its potential to go beyond slowing disease progression by directly impacting core drivers of IPF. With this mechanistic proof-of-biology in hand, we are well-positioned to advance toward the next stage of development. We believe GRI-0621 could represent a truly meaningful advance in the IPF treatment landscape, with the potential to create significant value for patients and shareholders alike.”
Study Met Exploratory Endpoints Demonstrating Increased Forced Vital Capacity, With Twice as Many Subjects Observed to Have No Decline in FVC Compared to Standard of Care at 12 Weeks
Placebo-adjusted changes from baseline in FVC increased by 99 ml in the GRI-0621-treated arm and a 139 ml increase in the subset taking both GRI-0621 and standard of care compared to placebo plus standard of care. Spirometry is subject to large visit-to-visit variability and is dependent on the individual’s effort, often resulting in data outliers. To minimize the impact of outliers in the dataset, a post hoc data analysis was performed excluding the datapoints with the largest gain or loss in FVC over 12 weeks from both arms. The results of this analysis demonstrated an increase in placebo-adjusted change from baseline in FVC of 54 ml in the GRI-0621-treated arm and an increase of 81 ml in the subset taking both GRI-0621 and standard of care. Overall, 39% of GRI-0621 treated subjects experienced an increase in FVC at 12 weeks compared to 80% of subjects who experienced a decline in FVC at 12 weeks in the placebo-treated arm.
The Phase 2a, randomized, double-blind, multinational, multi-center, placebo-controlled, parallel-design, 2-arm study enrolled 35 subjects with IPF who were randomized in a 2:1 ratio for GRI-0621 4.5mg or a placebo. GRI-0621 dose of 4.5mg was compared with a dose of placebo following once daily oral administration for 12 weeks. Concurrently, a sub-study examined the number and activity of immune cells in bronchoalveolar lavage (“BAL”) fluid in 8 subjects (across various centers). The primary endpoint for the Phase 2a study was safety and tolerability of oral GRI-0621 as assessed by clinical labs, vital signs and adverse events after 12 weeks of treatment. Secondary endpoints were baseline changes in serum biomarkers collected at week 6 and week 12; an assessment of the pharmacokinetics (PK) of GRI-0621 at the week 12 visit of treatment (steady state); and a determination of the pharmacodynamic activity of oral GRI-0621 as measured by inhibition of immune cell activation in blood after 6 weeks and 12 weeks, and from BAL fluid after 12 weeks of treatment in the sub-study. Additional exploratory endpoints for the study included assessment of the effect of GRI-0621 on pulmonary function at baseline and after 6 weeks and 12 weeks of treatment and flow cytometry and differential gene expression at various time points. These 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.
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 RARβγ agonist shown to inhibit the activity of key immune cells, like 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. For more information visit https://gribio.com/ or follow the company on X.
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