New IPF therapy modulates genes tied to inflammation and scarring
Phase 2a trial finds gene activity changes consistent with reduced lung injury
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New Phase 2a clinical trial data suggest that treatment with GRI-0621, an experimental oral therapy from GRI Bio, altered the activity of genes linked to inflammation and lung scarring (fibrosis) in adults with idiopathic pulmonary fibrosis (IPF).
The therapy was also associated with increased activity of genes involved in fibrosis resolution and lung tissue repair. Earlier data from the study (NCT06331624) showed that GRI-0621 was generally well tolerated when used alongside approved therapies and was observed to reduce lung injury and slow fibrosis progression, while helping preserve lung function over the study period.
“Across gene expression, [blood] biomarkers, immune profiles and lung function, we see a remarkably consistent picture emerge,” Marc Hertz, PhD, GRI Bio’s CEO, said in a company press release. “GRI-0621 appears to suppress ongoing injury, reduce fibrosis, and activate mechanisms associated with rebuilding damaged lung tissue.”
Understanding IPF and the limits of current treatments
IPF is a type of pulmonary fibrosis, marked by progressive lung scarring (fibrosis) that makes it harder for the lungs to take in oxygen. Common symptoms include shortness of breath, fatigue, and a dry, hacking cough.
A defining feature of IPF is the breakdown of the alveolar basement membrane — a thin layer of tissue that separates the alveoli, the tiny air sacs responsible for gas exchange, from the lung’s small blood vessels.
Two anti-fibrotic medications, Pirfenidone (sold as Esbriet and generics) and Ofev (nintedanib), are approved to slow lung function decline in people with IPF. However, they do not stop disease progression or reverse existing lung damage.
GRI-0621 is designed to reduce the activity of type 1 invariant natural killer T-cells (iNKT), immune cells thought to contribute to injury, inflammation, and fibrosis in IPF. The therapy works by activating retinoid acid receptors, which are known to play a role in dampening iNKT activity.
How researchers tested the experimental IPF therapy
The Phase 2a study enrolled 35 adults with IPF, ages 40 to 85, who were randomly assigned to receive 4.5 mg of GRI-0621 or a placebo once daily for 12 weeks (about three months). Most participants (80%) were also treated with pirfenidone or Ofev as standard of care.
Compared with placebo, treatment with GRI-0621 was associated with reduced activity of genes linked to lung injury and fibrotic tissue formation. Researchers also observed increased activity of genes involved in pathways related to fibrosis resolution and lung tissue repair.
These findings extend earlier trial data showing that GRI-0621 was generally well-tolerated and was associated with reductions in molecular markers linked to fibrosis and collagen production. The treatment was also associated with changes in T-cell receptor expression on iNKT cells. Lung function was assessed using forced vital capacity (FVC), with results suggesting preservation of lung function over the study period.
“The totality of data generated in this Phase 2a study suggests that GRI-0621 may represent a fundamentally different approach, with the potential to alter the trajectory of disease by promoting repair of damaged lung tissue,” Hertz said.
