TrialLineage Concept
Idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by irreversible scarring of lung tissue. It is the most common and severe form of idiopathic interstitial pneumonia, with a median survival of 3–5 years from diagnosis.
What is IPF?
IPF causes progressive replacement of normal lung tissue with dense scar tissue (fibrosis). The fibrosis occurs in the interstitium — the tissue surrounding the air sacs (alveoli) — reducing the lungs' ability to expand and exchange oxygen. Patients experience worsening breathlessness, chronic dry cough, and declining exercise capacity.
“Idiopathic” means no definitive external cause is identified. Risk factors include aging, cigarette smoking history, environmental exposures to dusts or fumes, and genetic predisposition. The disease primarily affects adults over 50.
Current understanding
IPF is now understood as a disease of aberrant wound healing rather than chronic inflammation. Repetitive microscopic injuries to the lung epithelium trigger fibroblast activation and excessive extracellular matrix deposition. The repair process fails to resolve, leading to progressive tissue remodeling.
Two approved antifibrotic therapies — pirfenidone and nintedanib — can slow the rate of decline in lung function but do not stop progression or reverse existing fibrosis. This has driven ongoing research into additional profibrotic signaling pathways, including lysophosphatidic acid (LPA) receptor signaling.
Connection to the IPF lineage
IPF is the disease target for the BMS-986278 trial. Understanding IPF as a disease of disordered fibroblast signaling — not inflammation — is what made targeting a specific profibrotic receptor (LPA1) a rational therapeutic strategy.