Kura Oncology, Inc. · NASDAQ:KURA

Kura Oncology — RAS-Targeted Drug Development Summit 2025

21 slides from Kura Oncology's conference presentation, Sep 18, 2025

  1. Slide 1: Farnesyl transferase inhibition restores RAS inhibitor sensitivity in tumors exhibiting innate or adaptive resistance

    Farnesyl transferase inhibition restores RAS inhibitor sensitivity in tumors exhibiting innate or adaptive resistance Ali Smith Kura Oncology, Inc., San Diego, CA RAS-Targeted Drug Development Summit 16-18 September 2025

  2. Slide 2: Disclosure Information

    Disclosure Information Employee and stockholder of Kura Oncology, Inc. 2

  3. Slide 3: Potential utility of pan-RAS inhibitors in KRAS-mutant CRC

    Potential utility of pan-RAS inhibitors in KRAS-mutant CRC Factors limiting efficacy of mutant-selective • Approved G12C-selective KRAS inhibitors only KRAS inhibitors in colorectal cancer target ~3% of colorectal cancers (CRCs) • CRCs are less responsive to mutant-selective KRAS inhibitors than lun

  4. Slide 4: Potential utility of pan-RAS inhibitors in KRAS-mutant CRC

    Potential utility of pan-RAS inhibitors in KRAS-mutant CRC • Approved G12C-selective KRAS inhibitors only target ~3% of colorectal cancers (CRCs) • CRCs are less responsive to mutant-selective KRAS inhibitors than lung cancers due to higher basal receptor tyrosine kinase (RTK) activity1,2 and freque

  5. Slide 5: Farnesyl transferase inhibitors (FTIs) sensitize tumors to targeted therapies via RHEB-mTORC1

    Farnesyl transferase inhibitors (FTIs) sensitize tumors to targeted therapies via RHEB-mTORC1 Single-agent targeted therapy FTI-based combinations 2 3 1 1 Smith, AE. et al. Cancer Res 2023. 83(19):3252-63. 2 Patel, HV. Smith, AE. et al. bioRxiv 2024.12.20.629824. 5 3 Gasendo, JG. et al. Cancer Res 2

  6. Slide 6: Mechanistic rationale for combined FTI and pan-RASi in CRC

    Mechanistic rationale for combined FTI and pan-RASi in CRC Does RTK-mediated (re)activation of PI3K-AKT-mTORC1 still occur in the presence of pan-RASi? Can the next-generation FTI KO-2806 enhance the activity of pan-RAS inhibition in CRC? ? 6

  7. Slide 7: Persistent mTORC1 signaling remains a liability with pan-RAS inhibition and is targetable with the FTI KO-2806

    Persistent mTORC1 signaling remains a liability with pan-RAS inhibition and is targetable with the FTI KO-2806 ? 7

  8. Slide 8: Persistent mTORC1 signaling remains a liability with pan-RAS inhibition and is targetable with the FTI KO-2806

    Persistent mTORC1 signaling remains a liability with pan-RAS inhibition and is targetable with the FTI KO-2806 Does this translate to in vivo combination activity? ? 8

  9. Slide 9: Preclinical models of KRAS-mutant CRC are largely resistant to pan-RASi

    Preclinical models of KRAS-mutant CRC are largely resistant to pan-RASi 1000 DLD-1 CR3150 CO-04-0002 LoVo SW620 HCT116 CR1245 SW480 GP2D G13D G12V G12D G13D G12V G13D G12D G12V G12D 800 600 400 % Change in tumor volume 200 (relative to baseline) 100 50 0 -50 -100 RMC-6236 (25 mg/kg po qd) 9

  10. Slide 10: Preclinical models of KRAS-mutant CRC are largely resistant to pan-RASi

    Preclinical models of KRAS-mutant CRC are largely resistant to pan-RASi Consistent with preliminary clinical data 1000 DLD-1 CR3150 CO-04-0002 LoVo SW620 HCT116 CR1245 SW480 GP2D G13D G12V G12D G13D G12V G13D G12D G12V G12D 800 600 400 % Change in tumor volume 200 (relative to baseline) 100 50 Revol

  11. Slide 11: KO-2806 enhances antitumor activity of RMC-6236 in preclinical CRC xenograft models

    KO-2806 enhances antitumor activity of RMC-6236 in preclinical CRC xenograft models 1000 DLD-1 CR3150 CO-04-0002 LoVo SW620 HCT116 CR1245 SW480 GP2D G13D G12V G12D G13D G12V G13D G12D G12V G12D 800 600 400 % Change in tumor volume 200 (relative to baseline) 100 50 0 -50 -100 RMC-6236 (25 mg/kg po qd

  12. Slide 12: KO-2806 enhances antitumor activity of RMC-6236 in preclinical CRC xenograft models

    KO-2806 enhances antitumor activity of RMC-6236 in preclinical CRC xenograft models What is the mechanism underlying this enhancement? 1000 DLD-1 CR3150 CO-04-0002 LoVo SW620 HCT116 CR1245 SW480 GP2D G13D G12V G12D G13D G12V G13D G12D G12V G12D 800 600 400 % Change in tumor volume 200 (relative to b

  13. Slide 13: Enhanced tumor growth inhibition by pan-RAS/KO-2806 combination correlates with deeper mTORC1 inhibition in vivo

    Enhanced tumor growth inhibition by pan-RAS/KO-2806 combination correlates with deeper mTORC1 inhibition in vivo GP2D 4000 KRASG12D CRC Vehicle 2000 KO-2806 (10 mg/kg po bid) Tumor volume (mm3) RMC-6236 (25 mg/kg po qd) 500 RMC-6236 + KO-2806 400 300 0.0041 200 100 0 0 10 20 30 Treatment days U F 13

  14. Slide 14: Enhanced tumor growth inhibition by pan-RAS/KO-2806 combination correlates with deeper mTORC1 inhibition in vivo

    Enhanced tumor growth inhibition by pan-RAS/KO-2806 combination correlates with deeper mTORC1 inhibition in vivo GP2D CO-04-0002 4000 KRASG12D CRC 3000 KRASG12D CRC Vehicle Vehicle 2000 KO-2806 (10 mg/kg po bid) KO-2806 (10 mg/kg po bid) Tumor volume (mm3) Tumor volume (mm3) RMC-6236 (25 mg/kg po qd

  15. Slide 15: Enhanced tumor growth inhibition by pan-RASi/KO-2806 combination correlates with deeper mTORC1 inhibition in vivo

    Enhanced tumor growth inhibition by pan-RASi/KO-2806 combination correlates with deeper mTORC1 inhibition in vivo GP2D CO-04-0002 4000 KRASG12D CRC 3000 KRASG12D CRC Vehicle Vehicle 2000 KO-2806 (10 mg/kg po bid) KO-2806 (10 mg/kg po bid) Tumor volume (mm3) Tumor volume (mm3) RMC-6236 (25 mg/kg po q

  16. Slide 16: Pan-RAS inhibition induces the activity of multiple HER-family receptors in vivo

    Pan-RAS inhibition induces the activity of multiple HER-family receptors in vivo GP2D CO-04-0002 4000 KRASG12D CRC 3000 KRASG12D CRC Vehicle Vehicle 2000 RMC-6236 (25 mg/kg po qd) RMC-6236 (25 mg/kg po qd) Tumor volume (mm3) Tumor volume (mm3) 500 2000 400 300 1000 200 100 0 0 0 10 20 30 0 10 20 30

  17. Slide 17: KO-2806/pan-RAS combination is superior to cetuximab/pan-RAS combination in GP2D CRC CDX model

    KO-2806/pan-RAS combination is superior to cetuximab/pan- RAS combination in GP2D CRC CDX model GP2D KRASG12D CRC 2000 Vehicle 1000 Cetuximab (0.25 mg/dose ip q3d) 1000 Tumor volume (mm3) RMC-6236 (10 mg/kg po qd) RMC-6236 + Cetuximab 500 KO-2806 (10 mg/kg po bid) RMC-6236 + KO-2806 0 0 10 20 30 Tre

  18. Slide 18: Potential benefit of KO-2806 in CRC tumors relapsing on pan- or mutant-selective RAS inhibitors

    Potential benefit of KO-2806 in CRC tumors relapsing on pan- or mutant-selective RAS inhibitors Is upfront co-administration required to enhance tumor growth inhibition? GP2D 4000 KRASG12D CRC Vehicle 2000 RMC-6236 (pan-RASi) Tumor volume (mm3) MRTX1133 (KRAS G12D-selective) 500 400 300 200 100 +KO-

  19. Slide 19: KO-2806 re-sensitizes CRC xenograft tumors relapsing on pan-RAS inhibitor; similar responses to upfront administration

    KO-2806 re-sensitizes CRC xenograft tumors relapsing on pan- RAS inhibitor; similar responses to upfront administration GP2D 2000 (KRASG12D CRC) 1000 Tumor volume (mm3) 500 400 +KO-2806 300 200 100 0 25 mg/kg RMC-6236 10 mg/kg KO-2806 19

  20. Slide 20: KO-2806 sensitizes CRC xenograft tumors relapsing on mutant-selective inhibitor to pan-RASi

    KO-2806 sensitizes CRC xenograft tumors relapsing on mutant-selective inhibitor to pan-RASi GP2D 3000 (KRASG12D CRC) 2000 1000 Tumor volume (mm3) 500 400 300 switch 200 100 0 10 mg/kg MRTX-1133 10 mg/kg KO-2806 20

  21. Slide 21: Conclusions

    Conclusions • Reactivation of mTORC1 signaling remains a liability of pan-RAS inhibitors that is targetable by KO-2806, enhancing antitumor effects in preclinical models of CRC • Basal EGFR activity is high in CRCs and pan-RASi induces additional HER-family receptors. As such, the combination of RMC

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