Fibrosis is the final common pathway in virtually all forms of chronic organ failure. The cell and molecular biology of fibrosis is similar whether it occurs in kidney, liver, lung or elsewhere and whether its cause is viral, chemical, physical or inflammatory. Fibrosis results from the excessive activity of fibroblasts, in particular from an activated form called the myofibroblast. The biology of these cells is well understood and there is consensus among experts that pharmacological attenuation of myofibroblast activity ought to slow or perhaps even reverse disease progression, thereby preserving organ function and prolonging healthy life.

What's missing is the clinical proof — evidence that agents that target the myofibroblast have a meaningful clinical effect in humans. That's the challenge we're taking on at Stromedix.

STX-100
STX-100 is Stromedix’ first clinical candidate.  It is a humanized monoclonal antibody targeting integrin αvβ6 in-licensed from Biogen Idec. STX-100 exhibits significant anti-fibrotic activity in preclinical models of lung, kidney and liver disease. Stromedix intends to develop this novel molecule in multiple clinical indications and began Phase 1 clinical testing in early 2008.


Relevant Publications
Hahm et al. αvβ6 integrin regulates renal fibrosis and inflammation in alport mouse.  Am J Pathol. 2007; 170: 110-125.

Horan et al. Partial inhibition of integrin αvβ6 prevents pulmonary fibrosis without exacerbating inflammation. Am J Respir Crit Care Med. 2008; 177(1):56-65. Epub 2007 Oct 4

Puthawala et al. Inhibition of integrin αvβ6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis. Am J Respir Crit Care Med. 2008; 1;177(1):82-90. Epub 2007 Oct 4.

Wang et al. Role of αvβ6 integrin in acute biliary fibrosis. Hepatology. 2007; 46(5):1404-12.

Trevillian  et al. αvβ6 Integrin expression in diseased and transplanted kidneys. Kidney Int 2004; 66(4): 1423-1433.

Weinreb et al. Function-blocking integrin αvβ6 monoclonal antibodies. J. Biol. Chem. 2004; 279(17): 17875-17887.

Munger et al. The integrin αvβ6 binds and activates latent TGFß1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 1999; 96: 319-328.