Kura Oncology, Inc. · NASDAQ:KURA

Kura Oncology — 5th RAS-Targeted Drug Development Summit 2023

20 slides from Kura Oncology's conference presentation, September 2023

1. Slide 1: Farnesyl Transferase Inhibitors - Evolution from Targeting HRAS to Overcoming Adaptive Resistance

   Farnesyl Transferase Inhibitors- Evolution from Targeting HRAS to Overcoming Adaptive Resistance to Targeted Therapies Shivani Malik 5th RAS-Targeted Drug Development Summit September 26-28, 2023

2. Slide 2: Disclosures

   Disclosures -Employee of Kura Oncology, Inc. 2

3. Slide 3: FTIs and the RAS Family of Oncogenes

   FTIs and the RAS Family of Oncogenes • Tipifarnib-first-in-class FTI, originally developed to target KRAS • Upon farnesyl transferase inhibition, KRAS and NRAS become geranylgeranylated • HRAS is an obligate farnesylation target-it lacks the geranylgeranylation rescue pathway FTase- Farnesyl transfe

4. Slide 4: Tipifarnib Demonstrates Durable Anti-Tumor Activity in HRAS-Mutant HNSCC

   Tipifarnib Demonstrates Durable Anti-Tumor Activity in Patients with Recurrent or Metastatic HRAS-Mutant HNSCC Patients with high variant allele frequency (VAF, ≥20%) mHRAS HNSCC ORR 55% N=20 evaluable patients Median OS 95% CI (months) Lower Upper HNSCC with high VAF, including 15.4 7.0 46.4 Red, P

5. Slide 5: Can FTIs Be Clinically Effective in a Broader HNSCC Population?

   Can FTIs Be Clinically Effective in a Broader HNSCC Population? Comprehensive genomic profiling using Tempus XT HRAS-PIK3CA crosstalk in HNSCC - Tipifarnib blocks reveals HRAS- and/or PIK3CA-dependence in HNSCC hyperactivated growth factor signaling at multiple nodes, including HRAS and RHEB 5

6. Slide 6: Combined Tipifarnib and Alpelisib Inhibits mTOR Reactivation for the Entire Dosing Interval

   Combined Tipifarnib and Alpelisib Inhibits mTOR Reactivation for the Entire Dosing Interval Reference: Smith et al., 2023, Tipifarnib potentiates the antitumor effects of PIK3Kα inhibition in PIK3CA- and HRAS- dysregulated HNSCC 6 via convergent inhibition of mTOR activity. Cancer Res, CAN-23-0282

7. Slide 7: RHEB, An Obligately Farnesylated Protein, is a Key FTI Target

   RHEB, An Obligately Farnesylated Protein, is a Key FTI Target Tipifarnib blocks localization of RHEB depletion enhances mTOR inhibition when RHEB to the lysosomes combined with alpelisib in PIK3CA mutant HNSCC cells CAL33 – PIK3CA H1047R Reference: Smith et al., 2023, Tipifarnib potentiates the anti

8. Slide 8: Durable Clinical Response Observed in Patient with PIK3CA-dependent HNSCC

   Durable Clinical Response Observed in Patient with PIK3CA-dependent HNSCC • 35yo, male, nonsmoker, HPV16 positive • SCC of tonsil Stage III cT4N2M0; PD-L1 CPS = 60 • Prior Treatments • CDDP/rad for 1 mo (Nov-Dec2019), BOR UNK • Cemiplimab/ISA101b (Jun-Nov2021), BOR PD • PIK3CA R88Q mutation (44%) an

9. Slide 9: Mechanism-Based Combinations Needed to Fully Realize the Potential of KRAS G12C Inhibitors

   Mechanism-Based Combinations Needed to Fully Realize the Potential of Breakthrough KRAS G12C Inhibitors pERK inhibition by KRASG12C inhibitors hyperactivates RTK signaling leading to ERK-RSK and/or mTOR-S6 pathway activation 9

10. Slide 10: Next-Generation FTI

    Next-Generation FTI Tipifarnib KO-2806 Potency: Good Improved potency, Selectiv ity: Excellent pharmacokinetic and Dose: 600 mg physicochemical Frequency: BID properties • FTIs represent an attractive therapeutic and commercial opportunity in oncology with compelling options in combination with othe

11. Slide 11: Tumor Growth Inhibition in KRASG12C-Mutant NSCLC PDX & CDX Models

    Tumor Growth Inhibition in KRASG12C-Mutant NSCLC PDX & CDX Models LU2512 2000 NCI-H2122 3000 (KRASG12C) NSCLC PDX (KRASG12C) CDX Tumor Volume (mm3) Tumor Volume (mm3) 2500 1500 2000 1500 1000 1000 *** 500 500 *** *** 0 Vehicle 0 0 5 10 15 20 25 30 0 5 10 15 20 25 30 KO-2806 Treatment Days Adagrasib

12. Slide 12: KO-2806 Deepens Signaling Inhibition by Adagrasib: Inhibition of MAPK Signaling

    KO-2806 Deepens Signaling Inhibition by Adagrasib in KRASG12C- Mutant NSCLC Tumor Spheroids: Inhibition of MAPK Signaling HER3 MAPK inhibition Cell cycle arrest & apoptosis 12

13. Slide 13: KO-2806 Deepens Signaling Inhibition by Adagrasib: Strong Inhibition of mTOR Signaling

    KO-2806 Deepens Signaling Inhibition by Adagrasib in KRASG12C- Mutant NSCLC Tumor Spheroids: Strong Inhibition of mTOR Signaling HER3 mTOR inhibition Cell cycle arrest & apoptosis 13

14. Slide 14: KO-2806 Deepens Signaling Inhibition by Adagrasib: HER3 Inhibition

    KO-2806 Deepens Signaling Inhibition by Adagrasib in KRASG12C- Mutant NSCLC Tumor Spheroids: HER3 Inhibition RTK inhibition HER3 Cell cycle arrest & apoptosis 14

15. Slide 15: KO-2806 Deepens Signaling Inhibition by Adagrasib: Induction of Cell Cycle Arrest and Apoptosis

    KO-2806 Deepens Signaling Inhibition by Adagrasib in KRASG12C-Mutant NSCLC Tumor Spheroids: Induction of Cell Cycle Arrest and Apoptosis HER3 Cell cycle arrest & apoptosis 15

16. Slide 16: KO-2806-Adagrasib Combination Reduces mTOR and RSK Activation, Increases Apoptosis

    KO-2806-Adagrasib Combination Reduces mTOR and RSK Activation, Increases Apoptosis and Blocks Proliferation in vivo Ki67 115.5 ± 10.4 75.1 ± 22.3 Cleaved Caspase 3 3.7 ± 1.0 16.3 ± 4.6 16

17. Slide 17: KO-2806-Adagrasib Combination Increases the Depth of Response

    KO-2806-Adagrasib Combination Increases the Depth of Response Compared to Adagrasib Monotherapy Vehicle Response calls based on mRECIST KO-2806 PD-Progressive disease SD-Stable disease Adagrasib - 100mg/kg, QD Adagrasib PR-Partial response KO-2806+Adagrasib 17

18. Slide 18: KO-2806-Adagrasib Combination Increases the Duration of Response

    KO-2806-Adagrasib Combination Increases the Duration of Response Compared to Adagrasib Monotherapy Vehicle KO-2806 ***- p<0.001 Adagrasib KO-2806+Adagrasib 18

19. Slide 19: Summary

    Summary • FTIs have the promise to enhance antitumor activity of targeted therapies in solid tumors • FTIs in combination with KRASG12C inhibitors drive tumor regressions and durable responses in preclinical NSCLC models • First demonstration of a durable clinical response with combination of FTI ti

20. Slide 20: Acknowledgements

    Acknowledgements The patients and their families Kura Oncology Translational Research group Francis Burrows Patel H et al. The next generation farnesyltransferase inhibitor, KO-2806, blocks Hetika Vora Patel oncogenic signaling at multiple nodes to enhance the antitumor efficacy of KRASG12C inhibito

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