New trial data show oral therapy alters immune pathways in adults with IPF
Phase 2a findings suggest GRI-0621 is engaging its intended targets
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Treatment with the experimental oral therapy GRI-0621 modulated immune cell activity in adults with idiopathic pulmonary fibrosis (IPF) in an early Phase 2a clinical trial, according to new data announced by its developer, Gri Bio.
Data from the Phase 2a study (NCT06331624) broadly suggest that GRI-0621 is working as designed and may help reduce inflammation and fibrotic activity in the lungs.
“GRI-0621 continues to demonstrate a compelling profile, combining favorable safety and tolerability with a dual mechanism of action as both an immunomodulator and an anti-fibrotic agent,” Marc Hertz, PhD, Gri Bio’s CEO, said in a company press release.
Understanding how IPF affects the lungs
IPF is a chronic disorder marked by inflammation and fibrosis in the lungs. GRI-0621 is designed to block the activity of type 1 invariant natural killer T-cells, or iNKTs — a specific kind of immune cell thought to play a central role in IPF-related inflammation and fibrosis.
In IPF, these iNKTs are thought to become abnormally activated, helping drive disease progression. Chronic activation is associated with reduced levels of a protein called TCR on the cells’ surface. The new data show that after about three months of daily GRI-0621 treatment, iNKTs in treated patients expressed higher levels of TCR compared with levels at the start of the study or in participants who received a placebo on standard of care. These findings suggest that GRI-0621 is reducing iNKT activity as intended.
The data also showed that GRI-0621 treatment increased levels of interferon-gamma, a signaling molecule linked to anti-fibrotic activity. At the same time, levels of several signaling molecules associated with fibrosis were reduced following treatment.
These findings add to previously announced top-line results from the trial, which showed that GRI-0621 was generally well tolerated and that patients given the therapy tended to experience improvements in measures of lung function and collagen turnover, a marker of fibrosis.
“Our Phase 2a study was intentionally designed to assess a broad range of clinical, biomarker, and mechanistic endpoints,” Hertz said. “The immune cell data announced today are highly consistent with our earlier findings on collagen turnover, lung tissue repair, and improvements in pulmonary function, further strengthening the overall clinical proof-of-concept for GRI-0621.”
