First Patient Dosed in Phase II Study of Tipifarnib

Kura Oncology, Inc. recently announced that the first patient has been dosed in the Phase II clinical trial of tipifarnib in patients with locally advanced tumors that carry HRAS mutations. Tipifarnib is an inhibitor of farnesylation, a key cell-signaling process implicated in cancer initiation and development.

“There are no approved treatments that target HRAS mutations specifically,” said Alan Ho, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center and a lead investigator on the Phase II trial. “We look forward to investigating whether tipifarnib can inhibit HRAS-mediated activation of the MAPK pathway to produce therapeutic responses.”

“Tipifarnib has previously demonstrated durable responses in subsets of patients with cancer,” added Antonio Gualberto, MD, PhD, Chief Medical Officer of Kura Oncology. “The selection of patients with tumors characterized by HRAS mutations represents a promising strategy to identify those patients most likely to benefit from tipifarnib.”

The HRAS protein is involved in regulating cell division in response to growth factor stimulation and other signals that instruct cells to grow or divide. HRAS is an early player in many signal transduction pathways and acts as a molecular on/off switch – once HRAS is turned on, it recruits and activates proteins necessary for the propagation of the signal. In certain tumors, mutations in the HRAS gene cause the HRAS protein to be permanently on, resulting in persistent activation of downstream growth and proliferation signals that drive tumor cell growth.

Farnesyl transferase inhibitors, such as tipifarnib prevent protein farnesylation, a key cell-signaling process implicated in cancer initiation and development. In preclinical studies, tipifarnib has been shown to block HRAS farnesylation and membrane localization, thereby inhibiting the growth and proliferation of HRAS mutant tumors. Collectively, cancers that have an HRAS mutation are estimated to have an annual incidence of approximately 8,000 patients in the US and, in general, patients with these cancers have poor prognosis and limited options for treatment.

The primary objective of the Phase II study will be to investigate the antitumor activity, in terms of objective response rate, of tipifarnib in patients with locally advanced, unresectable or metastatic, relapsed and/or refractory tumors that carry HRAS mutations. Secondary objectives include evaluation of progression-free survival, duration of response and safety. A total of 36 patients are planned to be enrolled into two non-randomized cohorts: malignant thyroid tumors with HRAS mutations; and non-hematological malignancies with HRAS mutations. Additional information about this clinical trial of tipifarnib is available at clinicaltrials.gov using identifier: NCT02383927.

Kura Oncology’s lead program, tipifarnib, is an inhibitor of farnesylation, a key cell- signaling process implicated in cancer initiation and development. In extensive clinical trials, tipifarnib has shown compelling and durable anti-cancer activity in certain patient subsets and a well-established safety profile. Preclinical and clinical data suggest that, in the right genetic context, tipifarnib has the potential to provide significant benefit to cancer patients with limited treatment options. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics, Kura Oncology will seek to identify patients most likely to benefit from tipifarnib. In addition to the Phase II clinical trial of tipifarnib in patients with tumors characterized by HRAS mutations, Kura Oncology intends to initiate a Phase II clinical trial in patients with peripheral T-cell lymphomas in the third quarter of 2015. Kura Oncology holds an exclusive license to develop and commercialize tipifarnib in the field of oncology, under an agreement with Janssen Pharmaceutica NV.

Kura Oncology is a clinical-stage biopharmaceutical company focused on the discovery and development of precision medicines for the treatment of solid tumors and blood cancers. Kura Oncology’s diverse pipeline consists of small molecules that target cancer-signaling pathways where there is a strong scientific and clinical rationale to improve outcomes by identifying those patients most likely to benefit from treatment. Kura Oncology’s approach to drug development is focused on rapidly translating novel science into life-saving medicines. For more information, visit www.kuraoncology.com.