Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — Technical Presentation (2025)
17 slides from Kura Oncology's technical presentation, 2025
Slide 1: Farnesyl transferase inhibitor KO-2806 enhances the anti-tumor activity of cabozantinib in renal cell carcinoma
Farnesyl transferase inhibitor KO-2806 enhances the anti-tumor activity of cabozantinib in renal cell carcinoma Jovylyn G. Gasendo, Stacia Chan, Hetika Vora Patel, Alison Smith, Linda Kessler, Francis Burrows, and Shivani Malik Kura Oncology, Inc., San Diego, CA
Slide 2: Disclosure Information
Disclosure Information Jovylyn G. Gasendo I have the following relevant financial relationships to disclose: ▪ Employee and stockholder of Kura Oncology, Inc. ▪ Holds patents and/or patent applications with Kura Oncology, Inc.
Slide 3: Advanced and metastatic RCC treatment landscape
Advanced and metastatic RCC treatment landscape Powles, T. et al. Annals of Oncology 2024; 35(8): 692-706.
Slide 4: Clinical activity of cabozantinib in post-VEGFR TKI and post-ICI settings
Clinical activity of cabozantinib in post-VEGFR TKI and post-ICI settings ❖ Cabozantinib is a tyrosine kinase inhibitor (TKI) that targets VEGFR2, c-Met, AXL, RET, KIT, Flt1/3/4, and Tie2.1 ❖ Cabozantinib is used in 2L+ lines of therapy in RCC due to proven activity in patients with prior anti-VEGFR
Slide 5: Rationale for using a farnesyl transferase inhibitor as a combination partner in RCC
Rationale for using a farnesyl transferase inhibitor as a combination partner in RCC ❖ Hyperactivated mTORC1 pathway is often observed with advanced RCC and is associated with poor prognosis. Rapalogs, including everolimus and temsirolimus, have been approved in RCC. However, they have had limited s
Slide 6: Rationale for using a farnesyl transferase inhibitor as a combination partner in RCC
Rationale for using a farnesyl transferase inhibitor as a combination partner in RCC ❖ Hyperactivated mTORC1 pathway is often observed with advanced RCC and is associated with poor prognosis. Rapalogs, including everolimus and temsirolimus, have been approved in RCC. However, they have had limited s
Slide 7: Exposure of primary endothelial cells to cabozantinib reduces VEGFR-mediated signaling pathways
Exposure of primary endothelial cells to cabozantinib reduces VEGFR-mediated signaling pathways
Slide 8: mTORC1 signaling is robustly diminished in primary endothelial cells exposed to KO-2806 plus cabozantinib
mTORC1 signaling is robustly diminished in primary endothelial cells exposed to KO-2806 plus cabozantinib
Slide 9: KO-2806 blocks RHEB farnesylation
KO-2806 blocks RHEB farnesylation
Slide 10: KO-2806 enhances the anti-angiogenic activity of cabozantinib in RCC xenografts
KO-2806 enhances the anti-angiogenic activity of cabozantinib in RCC xenografts 10 8 p < 0.0001 % CD31-positive Vehicle Cabozantinib KO-2806 Combination 6 4 CD31 2 (endothelial cell) 0 4 3 % NG2-positive p = 0.0115 NG2 2 (pericyte) 1 0 KI-12-0073 RCC PDX, Day 14 n b 6 e tio 80 i l tin ic h na -2 an
Slide 11: KO-2806 potentiates the anti-tumor activity of cabozantinib in various TKI-naïve RCC preclinical models
KO-2806 potentiates the anti-tumor activity of cabozantinib in various TKI-naïve RCC preclinical models 500 % Change in tumor volume Cabozantinib 250 KO-2806 + cabozantinib 50 0 -50 -100 51 97 73 6 1 O 32 i ak 6- 03 00 00 -0 78 C 2- 2- 2- KI -1 -1 -1 KI KI KI VHL status VHL Wildtype Mutant
Slide 12: RCC tumors progressing on anti-VEGFR TKIs respond to the combination of KO-2806 and cabozantinib
RCC tumors progressing on anti-VEGFR TKIs respond to the combination of KO-2806 and cabozantinib Caki1 RCC 2000 Vehicle Tumor volume (mm3) Axitinib 1500 1000 500 switch 0 Axitinib Days after treatment Axitinib Cabozantinib Axitinib Cabozantinib + KO-2806 0 7 14 21 28 35 42 Days after treatment
Slide 13: RCC tumors progressing on anti-VEGFR TKIs respond to the combination of KO-2806 and cabozantinib
RCC tumors progressing on anti-VEGFR TKIs respond to the combination of KO-2806 and cabozantinib Caki1 RCC 2000 70 (Best response vs day 14) % Tumor volume change Tumor volume (mm3) 1500 35 1000 0 p < 0.001 -35 500 switch -70 0 Axitinib Days after treatment Cabozantinib KO-2806 Axitinib Cabozantinib
Slide 14: RCC tumors progressing on anti-VEGFR TKIs respond to the combination of KO-2806 and cabozantinib
RCC tumors progressing on anti-VEGFR TKIs respond to the combination of KO-2806 and cabozantinib Caki1 RCC 1200 40 (Best response vs day 14) Vehicle % Tumor volume change Tumor volume (mm3) 900 20 600 0 p = 0.0524 300 -20 switch 0 -40 Lenvatinib Days after treatment Cabozantinib KO-2806 Lenvatinib C
Slide 15: Addition of KO-2806 halts RCC tumor progression on cabozantinib
Addition of KO-2806 halts RCC tumor progression on cabozantinib Caki1 RCC 1000 60 (Best response vs day 14) Vehicle % Tumor volume change Tumor volume (mm3) 40 750 20 500 0 p < 0.05 -20 250 add KO-2806 -40 0 -60 Days after treatment Cabozantinib Cabozantinib KO-2806 Cabozantinib Cabozantinib + KO-28
Slide 16: Key takeaways
Key takeaways ❖ KO-2806 enhances the anti-angiogenic activity of cabozantinib in RCC tumor models. • Mechanistically, KO-2806 achieves this by blocking mTORC1 signaling in endothelial cells, where the kinase plays an important role in proliferation, survival, and angiogenesis. ❖ Combination of KO-28
Slide 17: Acknowledgements
Acknowledgements ❖ Translational Research team at Kura Oncology, Inc.