About Cathepsins & Cancer

Extracellular proteases are involved in important stages of cancer malignancy. Cysteine cathepsins, particularly cathepsin L, B and S, have been implicated in many of these processes.

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Pan cathepsin inhibitor: VBY-825

VBY-825 for Primary Biliary Cirrhosis and NASH

VBY-825 is a potent inhibitor of multiple cathepsins, including cathepsins S and B. We believe inhibition of cathepsin S will suppress the autoimmune attack on the bile ducts and inhibition of cathepsin B will reduce and potentially reverse fibrosis. In our preclinical testing using standard disease models, we found that VBY-825 reduced liver fibrosis and treated autoimmunity. VBY-825 acts against two essential pathways in PBC pathology. We believe this dual mode of action has the potential to be a breakthrough treatment for PBC. In addition to PBC, we believe VBY-825 could be an effective treatment for nonalcoholic steatohepatitis, or NASH since it is a potent cathepsin B inhibitor. We plan to initiate a Phase 1 clinical trial with VBY-825 in healthy volunteers in the second half of 2015.

Primary Biliary Cirrhosis Overview

Primary biliary cirrhosis, or PBC, is a chronic liver disease in which the small bile ducts of the liver are slowly destroyed by chronic autoimmune attack. Significant damage to the bile ducts is accompanied by liver fibrosis which can, in turn, advance to cirrhosis and liver failure. Approximately 100,000 people in the United States have PBC, which qualifies it as an orphan disease. According to EvaluatePharma, worldwide sales of drugs for the treatment of PBC are expected to be over $800 million by 2020. Long- term studies report that a significant portion of such patients with advancing disease progress to liver failure, transplant or death within five to ten years, despite receiving ursodiol, the standard-of-care therapy.

NASH Overview

NASH is a serious liver disease in which fat accumulation in the liver induces chronic inflammation, leading in later stages to progressive fibrosis that may result in cirrhosis and liver failure. Approximately eight million people in the United States suffer from NASH, for which there is no currently approved disease-modifying therapeutic. In the United States, at least 900,000 NASH patients have advanced liver fibrosis or cirrhosis due to the disease. NASH is the third leading cause of liver transplant in the United States and accounts for 10% of liver transplants.

Development Status

We have tested VBY-825 in standard preclinical models of liver fibrosis and autoimmune disease. The results of such testing demonstrated that VBY-825 reduces liver fibrosis and attenuates autoimmunity in mice. These findings are consistent with our hypotheses regarding the effect of the inhibition of multiple cathepsins, including cathepsins S and B. We have also advanced VBY-825 through initial toxicology and cardiovascular safety studies. We believe the data from these studies supports advancing VBY-825 into IND-enabling safety studies in the second half of 2015.