WNT1-inducible signaling pathway protein-1 (WISP1) is a secreted matricellular protein shown to have a relevant role in fibrosis progression, making the protein a compelling target for anti-fibrosis therapeutics. MTX-463 is a first-in-class human IgG1 antibody designed to neutralize the WISP1-mediated fibrotic signaling that spans several fibrotic indications, including those in the lung and liver. A Phase 2 study of MTX-463 in patients with Idiopathic Pulmonary Fibrosis (IPF) is now open and more information can be found at: wispertrial.com

Ephrin ligands (like EphrinB2) and Eph receptors mediate biological processes involved in tissue fibrosis including cell migration, myofibroblast activation, and tissue remodeling. A growing body of evidence has implicated EphrinB2 in the fibrosis of the skin, lungs, and heart. MTX-474 is a first-in-class human IgG1 antibody designed to neutralize the EphrinB2 signaling that causes the onset and progression of fibrosis. A Phase 1 clinical study was completed in 1H-2025 in Australia (NCT06535841) and a Phase 2 study of MTX-474 in patients with Systemic Sclerosis (SSc) is anticipated to initiate in 2H-2025.

SMOC2 is a secreted matricellular protein that promotes extracellular matrix assembly, cell adhesion and fibrosis. In human studies across fibrotic indications, SMOC2 expression levels correlate with fibrotic disease severity and/or outcomes. Mediar is conducting optimization of lead SMOC2 antibodies with plans to nominate a clinical candidate in 1H-2025. Initial indications of interest include fibrosing diseases of the kidney.