Kura Oncology (KURA) investor relations material

Clinical trial updates and efficacy

• Darlifarnib plus cabozantinib achieved a 44% objective response rate and 94% disease control rate in heavily pretreated, cabozantinib-refractory clear cell renal cell carcinoma patients.

• Tumor shrinkage was observed in 75% of patients, with reductions between 32% and 47% among responders.

• Responses were durable, with some patients maintaining partial responses for nearly a year and treatment durations up to 56 weeks.

• The combination demonstrated a favorable and manageable safety profile, with most adverse events being manageable and not impacting quality of life.

• Activity was noted even in patients with stable disease on prior cabozantinib and across all darlifarnib dose levels.

Study design and patient characteristics

• FIT-001 is a first-in-human, multicenter, open-label phase 1a/b study evaluating darlifarnib alone and with cabozantinib in advanced solid tumors, including ccRCC.

• Patients had a median age of 67, all had prior IO-based therapy and cabozantinib, and most had exposure to other TKIs.

• The study evaluates darlifarnib at 3, 5, or 8 mg (7 days on/off) with cabozantinib at 60 or 40 mg daily.

• The study has advanced into Phase 1b dose expansion to determine the optimal biologically active dose and is enrolling cabozantinib-naive patients.

• Results were presented at the 2026 International Kidney Cancer Symposium: Europe.

Mechanistic rationale and combination strategy

• Darlifarnib is a next-generation farnesyl transferase inhibitor optimized for precision combinations, blocking Rheb and disrupting mTORC1 signaling.

• The combination targets complementary pathways: cabozantinib blocks VEGFR signaling, while darlifarnib inhibits mTORC1 via RHEB farnesylation.

• The approach is generalizable to other TKIs and targeted therapies, including KRAS and PI3K inhibitors.

• Preclinical studies show darlifarnib can block tumor growth and angiogenesis, with a more favorable safety profile than first-generation mTOR inhibitors.

• The strategy aims to establish a new standard for IO-refractory, second-line-plus ccRCC and may extend to other solid tumors.