COMP and systemic sclerosis: The first trial of CAT-192, a recombinant human antibody that neutralizes TGF-β1, was not successful.42 However, a more recent study tested fresolimumab, a first-in-class human IgG4 κ monoclonal antibody capable of neutralizing all mammalian isoforms of TGF-β.29 There is a four-gene, pharmacodynamic biomarker of SSc skin disease, based on gene expression in a mid-forearm skin biopsy.29 Two of the four genes making up the biomarker, thrombospondin-1 (THBS1) and cartilage oligomeric protein (COMP), are highly regulated by TGF-β.