GRI-0621 Improves FVC, Reduces Fibrotic Biomarkers in IPF

GRI-0621, an oral retinoic acid receptor beta/gamma (RARβ/γ)-selective agonist, produced a placebo-adjusted increase in forced vital capacity (FVC) and reduced markers of fibrotic remodeling in patients with idiopathic pulmonary fibrosis (IPF), according to phase 2a data presented at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain, held September 5 to 9.¹

IPF is driven by epithelial injury, immune dysregulation, and excess extracellular matrix, and approved antifibrotics slow disease decline but do not restore lung architecture, according to the study investigators.¹ GRI-0621-IPF-02 (NCT06331624) is a phase 2a, randomized, double-blind, placebo-controlled trial evaluating GRI-0621, a molecule from GRI Bio also known generically as tazarotene.¹

“The breadth of data being presented at ERS marks an important step forward for GRI-0621 and our understanding of its potential in IPF,” said Marc Hertz, PhD, chief executive officer of GRI Bio.² “We believe these findings provide a compelling foundation for the continued advancement of GRI-0621 and reinforce our conviction in its potential to meaningfully impact the treatment landscape for patients with IPF.”

GRI-0621 improves FVC in the GRI-0621-IPF-02 trial

GRI-0621-IPF-02 randomized 35 patients with IPF in a 2:1 ratio to oral GRI-0621 4.5 mg once daily (n = 23) or placebo (n = 12) for 12 weeks, with 80% of patients receiving background pirfenidone or nintedanib.¹ Endpoints included adverse events, RNA sequencing, serum collagen and injury biomarkers, flow cytometry immune phenotyping, and FVC.¹ Findings from the trial were presented across a late-breaking oral presentation and 3 posters covering lung function, translational biomarkers, and safety.²

Placebo-adjusted FVC change was +99 mL overall and +139 mL among patients also receiving background antifibrotic therapy.¹ The proportion of patients with no FVC decline rose to 39% with GRI-0621 versus 20% with placebo, while the proportion with a decline of 10% or more fell to 8% versus 20% with placebo.¹ A pre-specified per-protocol analysis showed a similar placebo-adjusted FVC benefit, surpassing the estimated 30 to 40 mL of natural-history decline expected over 12 weeks, according to the poster.¹

GRI-0621 reduces fibrotic biomarkers with favorable tolerability

Biomarker analyses showed GRI-0621 reduced type III and VI collagen formation while increasing collagen degradation, increased type IV collagen formation, and lowered neutrophil, macrophage, and pro-fibrotic T-helper 2 (Th2) cell activity relative to placebo.¹ Whole-blood RNA sequencing identified concordant transcriptional changes across curated anchor genes linked to fibrosis, epithelial injury, and tissue repair pathways, according to the poster.¹

GRI-0621 was well tolerated; the most common adverse events were mild dry lips (30%), dry skin (22%), and musculoskeletal symptoms (13%).¹ Patients treated with GRI-0621 reported less cough (0% versus 25% with placebo), dyspnea (4% versus 17%), and diarrhea (13% versus 33%), with no cases of weight loss compared with 17% among patients receiving placebo.¹ Investigators noted these tolerability findings held despite most patients continuing background pirfenidone or nintedanib, both of which carry their own gastrointestinal and dermatologic adverse effects.¹

Investigators said the convergent molecular, biomarker, immune, and functional signals support larger, adequately powered trials of GRI-0621 in IPF.¹ GRI-0621, known generically as tazarotene, received FDA orphan drug designation for IPF in June 2026, potentially providing a pathway to 7 years of US market exclusivity upon approval.³ The oral presentation and posters were delivered by investigators from University College London, University Hospitals Birmingham, Edinburgh, Cambridge, and other UK and international sites collaborating with GRI Bio.²

References

1. Parfrey H, Porter J, Saunders P, et al. Safety, translational biomarkers and lung function with the oral RARβ/γ-selective agonist GRI-0621 in idiopathic pulmonary fibrosis: a Phase 2a randomised, double-blind, placebo-controlled trial (GRI-0621-IPF-02). Abstract OA2380/63931. Presented at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.

2. GRI Bio, Inc. GRI Bio to present late-breaking Phase 2a GRI-0621 data highlighting lung function, anti-fibrotic biomarkers and favorable tolerability in IPF at ERS 2026. Published August 24, 2026. Accessed September 6, 2026. https://www.globenewswire.com/news-release/2026/08/24/3349779/0/en/gri-bio-to-present-late-breaking-phase-2a-gri-0621-data-highlighting-lung-function-anti-fibrotic-biomarkers-and-favorable-tolerability-in-ipf-at-ers-2026.html

3. GRI Bio, Inc. GRI Bio secures FDA orphan drug designation for GRI-0621 (tazarotene) in idiopathic pulmonary fibrosis. Published June 18, 2026. Accessed September 6, 2026. https://www.globenewswire.com/news-release/2026/06/18/3314182/0/en/gri-bio-secures-fda-orphan-drug-designation-for-gri-0621-tazarotene-in-idiopathic-pulmonary-fibrosis.html