About Cathepsin S & Autoimmune Diseases

Cathepsin S plays a key role in the pathology of autoimmune disease and in the maintenance of neuropathic pain. Genetic and pharmacologic inhibition of cathepsin S results in amelioration of disease in pharmacology models.

Learn more

Cathepsin S inhibitor: VBY-036 for Neuropathic Pain and Crohn's Disease

VBY-036 for Treatment of Neuropathic Pain:

VBY-036, is a potent and selective cathepsin S inhibitor. Cathepsin S appears to be a key mediator of a process pivotal in developing neuropathic pain, and by inhibiting cathepsin S, VBY-036 should prevent or substantially reduce pain.

We have completed Phase 1 clinical trials of VBY-036 in 124 healthy volunteers, evaluating the safety and pharmacokinetics of the drug by oral administration. Biomarkers used in these trials confirmed robust inhibition of cathepsin S at a range of doses. In addition, VBY-036 was well tolerated at all doses we tested.

We believe VBY-036 or an alternative cathepsin S inhibitor compound has the potential to more effectively treat neuropathic pain without the side effects experienced with existing therapies, such as opioid drugs. We retain worldwide rights to VBY-036 in all indications. More than 15 million people in the United States and Europe suffer from chronic neuropathic pain. According to Datamonitor, in 2014, sales of neuropathic pain therapies are projected to exceed $2.4 billion in the United States.

Efficacy in Chemotherapy-Induced Peripheral Neuropathy Disease Model

We have assessed VBY-036 in a variety of well-accepted preclinical models of neuropathic and inflammatory pain. As set forth in the graphic below, VBY-036 was shown to be efficacious in a mouse model of chemotherapy-induced peripheral neuropathy, or CIPN, in which neuropathic pain was induced by repeated administration of the chemotherapy agent paclitaxel. When dosing of VBY-036 was stopped, some efficacy was maintained for at least ten days, and there was no rebound, or immediate increase, in pain. Instead, there was a slow return of pain that remained responsive to cathepsin S inhibition when dosing resumed.

Efficacy of VBY-036 in a model of CIPN

Efficacy of VBY-036 in a model of CIPN

VBY-036 for Treatment of Crohn’s Disease:

Cathepsin S also appears to be a critical enzyme in the modulation of the immune system and the development of autoimmune diseases. Of the autoimmune diseases, we have chosen to focus first on Crohn’s disease due to the elevated levels of cathepsin S observed in patients and the effectiveness of VBY-036 in a widely-used preclinical mouse model of Crohn’s disease.

We believe VBY-036 has the potential to treat Crohn’s disease in a more effective manner than current therapies and more convenient manner than current biological therapies. Crohn’s disease affects approximately 900,000 people in the United States and Europe. In 2013, Crohn’s disease therapies generated sales of more than $2.9 billion in the United States.

Example of Efficacy in a Crohn’s Disease Model

We have assessed VBY-036 in a preclinical model of inflammatory bowel disease, or IBD, which shares many of the clinical features of Crohn’s disease. In this disease model, we administered VBY-036 once daily to rodents with doses that achieved plasma concentrations high enough to sustain inhibition of cathepsin S. The mice receiving VBY-036 experienced reduced disease severity. In this model, as shown in the graphic below, VBY-036 reduced intestinal weight/length ratios, a standard parameter in Crohn’s disease models, to normal levels. The efficacy of VBY-036 was similar to that observed with sulfasalazine, a disease-modifying anti-inflammatory drug used clinically. The results of this study suggest that inhibition of cathepsin S with VBY-036 may provide therapeutic benefit in human Crohn’s disease.

VBY-036 reduction of colon weight/pre-flush length in a model of IBD

VBY-036 reduction of colon weight/pre-flush length in a model of IBD