Kura Oncology hosted an analyst and investor event showcasing compelling preclinical data for its next-generation farnesyl transferase inhibitor (FTI) KO-2806, also known as darlifarnib, demonstrating its potential to overcome drug resistance when combined with major classes of targeted cancer therapies. The San Diego-based clinical-stage biopharmaceutical company presented findings that could transform treatment approaches across diverse tumor types.
Addressing Critical Resistance Mechanisms
The preclinical data illustrates how KO-2806 can enhance the anti-tumor activity of PI3Kα inhibitors, KRAS inhibitors, and antiangiogenic tyrosine kinase inhibitors (TKIs) by targeting common resistance pathways. According to Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology, "Innovation in cancer therapy demands not just new drugs, but smarter combinations to confront resistance head-on."
Innate and adaptive resistance mechanisms significantly limit the long-term efficacy of monotherapy with these targeted agents, underscoring the critical need for combination approaches. Kura's research demonstrates that FTIs potently suppress mTOR signaling, a clinically validated target, driving enhanced anti-tumor activity when combined with these therapeutic classes.
Superior Next-Generation Design
KO-2806 represents Kura's optimized, next-generation FTI, specifically designed to provide superior potency, pharmacokinetics, and physicochemical properties compared to first-generation candidates. In a broad panel of genetically-defined, in vivo tumor models, the compound showed robust preclinical activity across multiple therapeutic combinations.
The preclinical results demonstrate class-wide applicability, with multiple agents from each targeted therapy class showing broad mechanistic overlap. This suggests KO-2806's potential extends across entire therapeutic classes rather than being limited to specific agents.
Re-Sensitization in Relapsed Disease
Particularly compelling data emerged from preclinical non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) models, where KO-2806 successfully re-sensitized tumors to both mutant-selective and pan-KRAS inhibitors. This re-sensitization restored responsiveness in models representing relapsed disease settings, addressing a critical unmet medical need.
Expansive Patient Population Potential
The commercial opportunity for KO-2806 combinations appears substantial. When combined with cabozantinib or other TKIs, KO-2806 could address critical treatment gaps in renal cell carcinoma (RCC) and neuroendocrine tumors (NET). Extending to KRAS- and PI3Kα-mutant cancers in NSCLC, CRC, breast cancer and beyond, KO-2806 has the potential to impact more than 200,000 incident patients in the U.S. annually.
Clinical Development Progress
Kura is currently conducting three Phase 1 trials with its FTI program. The company plans to present preliminary clinical data at the European Society of Medical Oncology (ESMO) Congress 2025 in October, marking the first clinical insights from KO-2806.
The ESMO presentations will include:
- KO-2806 in combination with cabozantinib in renal cell carcinoma from the FIT-001 phase 1 trial
- KO-2806 as monotherapy in advanced solid tumors
- Tipifarnib and alpelisib combination results in recurrent/metastatic head and neck squamous cell carcinoma from KURRENT-HN
Pioneering FTI Innovation
Kura has established itself as a pioneer in farnesyl transferase inhibition discovery and development. The company's research focuses on targeting mTOR to overcome drug resistance and amplify the impact of targeted oncology therapeutics when paired with an FTI.
A second analyst event is scheduled for October 18, 2025, where Kura will review the clinical data presented at ESMO Congress 2025, providing comprehensive insights into the clinical potential of their FTI program.
