GRI Bio (NASDAQ:GRI) highlighted newly reported Phase 2A data for its lead idiopathic pulmonary fibrosis (IPF) program during a healthcare-focused Corporate Connect event, outlining safety results, biomarker trends, and early lung function signals that the company believes support continued development. President, CEO, and Director Marc Hertz also discussed a separate pipeline program aimed at autoimmune disease and outlined upcoming milestones.
Focus on immune modulators for inflammatory and fibrotic disease
Hertz described GRI Bio as a clinical-stage biopharmaceutical company developing immune modulators for inflammatory, fibrotic, and autoimmune diseases. He said the company is advancing two primary platform approaches:
- An oral retinoic acid receptor (RAR) beta-gamma agonist program, led by GRI-0621, aimed at addressing key drivers of fibrosis.
- NKT-cell modulator programs targeting a regulatory T-cell population the company calls dNKT cells, supported by a library of roughly 500 proprietary compounds.
IPF market context and Phase 2A study design
Hertz framed IPF as an orphan indication primarily affecting patients in their mid-60s, describing it as a progressive disease marked by lung scarring and fibrosis with a median survival of about three to five years. He said there is no cure other than lung transplantation, which he characterized as difficult to access.
He noted that two marketed drugs—nintedanib and pirfenidone—were standard of care at the time of the study, and that a third drug has since been approved. Hertz said these therapies can slow lung function decline but do not change the overall disease course or meaningfully impact survival, and he emphasized tolerability issues that can lead many patients to discontinue within the first year. Despite these limitations, he said the category generates more than $4 billion in annual sales.
GRI Bio’s Phase 2A IPF study enrolled 35 subjects randomized 2:1 between active and control arms, with a 12-week treatment period. Hertz said background therapy with nintedanib or pirfenidone was permitted as long as dosing remained stable, and that about 80% of participants were on one of those agents. He said the primary endpoints were safety and tolerability, with secondary endpoints focused on biomarkers and exploratory endpoints including lung function.
Safety, tolerability, and biomarker signals highlighted
Hertz said the study met its primary endpoints, with GRI-0621 “safe and well-tolerated.” He added that this profile was consistent with earlier studies of the molecule in more than 1,700 patients treated for up to one year. He also emphasized that the company did not observe overlapping gastrointestinal (GI) toxicities in patients taking standard-of-care therapies, which he said could position the drug for combination use.
On adverse events, Hertz said the GRI-0621 arm showed effects such as dry lips, dry skin, and muscle and joint pains, which he described as expected. He also said the company observed decreases in diarrhea and cough—two adverse events he associated with standard-of-care therapy—and said it was encouraging that those issues were not exacerbated.
Hertz said clinical chemistry findings showed no meaningful changes in the parameters presented, including liver aminotransferases, triglycerides, and cholesterol, and he noted a slight improvement in ALT that he said was consistent with prior studies.
Most of the reported efficacy-related readouts were biomarker-based. Hertz said the trial included extensive biomarker work, including flow cytometry, serum biomarkers of collagen turnover, and RNA sequencing for differential gene expression. He described a focus on collagen remodeling rates—balancing synthesis and degradation—to assess whether fibrosis is worsening or resolving. Using type 6 collagen as an example, he said the company saw decreased synthesis and increased degradation compared with standard of care, shifting remodeling rate signals toward a “fibrolytic response.” He said similar patterns were observed for type 1 and type 3 collagen, including an epitope associated with cross-linked type 3 collagen found in fibrotic tissue.
Hertz also discussed type 4 collagen, which he described as a major component of the alveolar basement membrane that is damaged in IPF. He said results suggested increased synthesis and decreased degradation of type 4 collagen compared to control, which he characterized as a signal consistent with rebuilding the basement membrane and initiating a lung repair mechanism.
From flow cytometry, Hertz said the company observed a shift from a pro-fibrotic to an anti-fibrotic immune environment, including reduced IL-4 in treated arms compared with control. He also cited gene expression signals that he said were consistent with basement membrane repair and epithelial cell repair, including AT2 epithelial cells transitioning to AT1 cells.
Exploratory lung function readouts and next steps
Hertz described the lung function data as exploratory, focusing on forced vital capacity (FVC) over the 12-week period. He said the GRI-0621 arm showed a higher proportion of subjects with preserved or increased FVC, and fewer subjects experiencing a decline of 10% or greater. Specifically, he said preservation/increase in FVC rose from 20% in the standard-of-care arm to 39% in the GRI-0621 arm, and that the proportion experiencing a decline of at least 10% dropped from 20% to about 8%.
In the question-and-answer session, Hertz cautioned that Phase 2A is an early “signal-seeking” study, but said the biomarker package suggested the potential not only to slow decline but to halt disease progression and possibly reverse aspects of disease biology. He reiterated that safety and tolerability could be important for combination approaches, and said the company has presented preclinical combination data previously.
On competitive positioning, Hertz said he believes differentiation could include an epithelial repair mechanism and a strong safety profile, while noting the early stage of the data.
He also said the company is open to partnerships, describing Phase 2B—potentially a pivotal study—as expensive and suggesting an ideal partner would bring complementary resources and expertise. He did not provide details on specific ongoing discussions.
Regarding milestones, Hertz said the company’s next steps for GRI-0621 include preparation for Phase 2B, including manufacturing and feasibility work. He also said the company plans to advance its dNKT-focused lead molecule, GRI-0803, through IND-enabling studies with the goal of opening an IND later this year, initially targeting systemic lupus erythematosus (SLE). Hertz noted that preclinical studies of dNKT or T-regulatory activators showed reductions in inflammation, restoration of kidney glomerular anatomy, reduced fibrosis, reductions in double-stranded anti-DNA antibodies, improved survival, and improvements in proteinuria-related endpoints.
About GRI Bio (NASDAQ:GRI)
GRI Bio, Inc, a clinical-stage biopharmaceutical company, focuses on treating inflammatory, fibrotic, and autoimmune diseases in the United States. Its product pipeline comprises GRI-0621, which is in phase II clinical development for the treatment of idiopathic pulmonary fibrosis; GRI-0803 which is in phase I trial for the treatment of systematic lupus erythematosus; GRI-0124, which is in pre-clinical development for the treatment of primary sclerosing cholangitis; and GRI-0729 in pre-clinical development.
