VBY-825

Description: VBY-825 is a novel, potent and reversible cathepsin inhibitor with high activity against cathepsins B, L, S and V. VBY-825 had no effect on body weight or IgG2b level, frequency of softtissue tumors or intraosseous tumor area. VBY-825 decreased total andMOLA, consistent with inhibited resorption. There was also a trend of increased relative trabecular bone area. Serum TRACP 5b activity in theVBY-825 treated group did not differ from the respective vehicle group, whereas the number of osteoclasts at tumor-bone interface was increasedin VBY-825 treated animals. These findings suggest that VBY-825decreased osteoclast function and resorption activity without decreasingthe number of osteoclastsIn conclusion, VBY-825 had no effects on tumor growth but it inhibitedbone destruction in this mouse model of MM, which is consistent with itspotency on cathepsin S and K, which are known to be important inosteoclast-mediated bone resorption. VBY-825 is a promising candidatefor the treatment of tumor-associated bone disease.

References:

1. Identificationand pre-clinical testing of a reversible cathepsin protease inhibitorreveals anti-tumor efficacy in a pancreatic cancer model. Biochimie.2010 Nov; 92(11):1618-24.

2. Proceedings of the 105th Annual Meeting of the American Association forCancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014; 74(19 Suppl):Abstract nr 1803.doi:10.1158/1538-7445.AM2014-1803