Kura Pipeline

Tipifarnib – HRAS Mutant Tumors

Our lead drug candidate, tipifarnib, is an inhibitor of protein farnesylation, a key cell signaling process implicated in cancer initiation and development. Tipifarnib has been studied in more than 5,000 patients and has demonstrated anti-cancer activity in certain patient subsets and a well-established safety profile. Clinical and preclinical data suggest that in the right therapeutic context, tipifarnib has the potential to provide significant benefit to cancer patients with limited treatment options.

Farnesyl transferase inhibitors (FTIs) such as tipifarnib prevent protein farnesylation, a key cell signaling process implicated in cancer initiation and development. In certain tumors, mutations in HRAS or its upstream effectors cause it to be permanently on, resulting in persistent activation of downstream growth and proliferation signals that drive tumor cell growth. FTIs work to prevent the aberrant growth and proliferation of cells that are dependent on these signaling pathways by switching HRAS off. Tipifarnib has been shown to inhibit HRAS function. Specifically, by blocking HRAS farnesylation and subsequent membrane localization, tipifarnib inhibits oncogenic, HRAS-driven cellular transformation in vitro and in vivo.

We have observed encouraging signs of clinical activity of tipifarnib in patients with HRAS mutant head and neck squamous cell carcinomas (SCCHN). Although our data set is small, we believe that the activity we observed is meaningful because of the setting: HPV negative, relapsed/refractory head and neck squamous cell carcinoma. This patient population has an overall survival of approximately 6-8 months and few therapeutic options, and new therapies, including immunotherapy, typically show a response rate in the range of 10-20%.

We are focusing the second stage of our ongoing Phase 2 trial on evaluating the activity of tipifarnib in patients with HRAS mutant SCCHN.