Fibroinflammation

Fibrosis is usually described as the end stage of chronic inflammation — the scar left behind. That framing is misleading. Fibrosis is an active, inflammatory process, and the two are so tightly coupled that the term fibroinflammation better describes what is actually happening in the tissue.

The mechanism

Persistent immune activation — from injury, autoimmunity, metabolic stress, or infection — keeps macrophages in a pro-fibrotic state. These macrophages release TGF-β and PDGF, which activate fibroblasts and drive their transformation into myofibroblasts. Myofibroblasts deposit collagen, stiffen the tissue, and further amplify inflammation through mechanotransduction.

The result is a self-sustaining loop: inflammation drives fibrosis, and fibrosis drives more inflammation. Interrupting only one arm of the loop rarely reverses the disease.

Where it occurs

• Idiopathic pulmonary fibrosis — progressive scarring of the lung interstitium, with a median survival of 3–5 years from diagnosis.
• Nonalcoholic steatohepatitis (NASH/MASH) — inflammation and fibrosis of the liver, a leading cause of cirrhosis.
• Chronic kidney disease — tubulointerstitial fibrosis is the final common pathway of most progressive kidney disease.
• Systemic sclerosis — fibrosis of skin and internal organs driven by autoimmune vascular injury.

Our approach

We are developing a bispecific antibody that simultaneously blocks a pro-fibrotic cytokine and activates a pro-resolving receptor on macrophages. In preclinical models this dual action reduced established fibrosis rather than merely slowing progression — a bar that single-agent anti-fibrotics have generally failed to clear.