Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — Investor Presentation (January 2023)
34 slides from Kura Oncology's investor presentation, Jan 9, 2023
Slide 1: Developing Precision Medicines for the Treatment of Cancer
DEVELOPING PRECISION MEDICINES FOR THE TREATMENT OF CANCER Corporate Presentation – January 2023 Exhibit 99.1
Slide 2: Forward-Looking Statements
FORWARD-LOOKING STATEMENTS This presentation contains forward-looking statements. Such statements include, but are not limited to, statements regarding our research, preclinical and clinical development activities, plans and projected timelines for ziftomenib, tipifarnib and KO-2806, plans regarding
Slide 3: Investment Highlights
INVESTMENT HIGHLIGHTS * Unaudited, preliminary cash, cash equivalents and short-term investments as of 12/31/22 Targeted Oncology Advancing a pipeline of novel therapies, forging new scientific and clinical paths to give patients a better chance for long-term durable remissions Proprietary Pipeline
Slide 4: Kura Leadership Team and Board of Directors
KURA LEADERSHIP TEAM AND BOARD OF DIRECTORS Leadership Team Board of Directors Troy Wilson, Ph.D., J.D. President & Chief Executive Officer Teresa Bair, J.D. Chief Legal Officer Troy Wilson, Ph.D., J.D. Chairman Helen Collins, M.D. Steven Stein, M.D. Thomas Malley Diane Parks Carol Schafer Mary Szel
Slide 5: Drug Candidate Pipeline
DRUG CANDIDATE PIPELINE PROGRAM CLINICAL TRIAL STUDY STARTUP PHASE 1 REGISTRATION DIRECTED ZIFTOMENIB Menin Inhibitor KOMET-001 Monotherapy KOMET-007/008 Combination with standards of care TIPIFARNIB Farnesyl Transferase Inhibitor (FTI) AIM-HN Monotherapy KURRENT-HN Combination with alpelisib KURREN
Slide 6: Ziftomenib: Menin-KMT2A/MLL Inhibitor in Acute Leukemias
ZIFTOMENIB: MENIN-KMT2A/MLL INHIBITOR IN ACUTE LEUKEMIAS
Slide 7: NPM1-Mutant and KMT2A-Rearranged AML Represent Areas of Significant Unmet Need
NPM1-MUTANT AND KMT2A-REARRANGED AML REPRESENT AREAS OF SIGNIFICANT UNMET NEED No FDA-Approved Targeted Therapies Exist Today 1 SEER statistics for AML in the US, accessed April 2020. 2 Döhner et al. Blood. 2017 Jan 26;129(4):424-447. 3 Angenendt L, et al. J Clin Oncol. 2019;37(29):2632-2642. 4. Ve
Slide 8: Ziftomenib Is a Potent and Selective Oral Inhibitor of the Menin-KMT2A/MLL Complex
ZIFTOMENIB IS A POTENT AND SELECTIVE ORAL INHIBITOR OF THE MENIN-KMT2A/MLL COMPLEX Kühn MW, et al. Cancer Discov. 2016;6(10):1166-1181 Thorsteinsdottir U, et al. Mol Cell Biol. 2001;21(1):224-234 Patel SS, et al. Curr Hematol Malig Rep. 2020;15(4):350-359 Brunetti L, et al. Cancer Cell. 2018;34(3):4
Slide 9: KOMET-001 Phase 1 Clinical Trial of Ziftomenib in R/R AML
KOMET-001 PHASE 1 CLINICAL TRIAL OF ZIFTOMENIB IN PATIENTS WITH RELAPSED OR REFRACTORY (R/R) AML PHASE 1A DOSE ESCALATION PHASE 1B VALIDATION COHORTS PHASE 1B EXPANSION 50 mg ~ ~ 100 mg 1000 mg Cohort 1: 200 mg Cohort 2: 600 mg OBJECTIVES Dose escalation in all-comer patients to establish maximum t
Slide 10: Ziftomenib Demonstrates Encouraging Safety Profile and Tolerability in Phase 1b
ZIFTOMENIB DEMONSTRATES ENCOURAGING SAFETY PROFILE AND TOLERABILITY IN PHASE 1B ≥Gr 3 TEAEs Occurring in >10% Participants (Regardless of Causal Assessment) 200 mg 600 mg NPM1-m (N = 4) (N = 20) 0 0 KMT2A-r (N = 13) (N = 16) Differentiation Syndrome 4 (30.8) 4 (25.0) Febrile Neutropenia 0 2 (12.5) E
Slide 11: Characterization of Differentiation Syndrome with Ziftomenib
CHARACTERIZATION OF DIFFERENTIATION SYNDROME WITH ZIFTOMENIB Erba et al. ASH 2022 #64 (preliminary data as of October 24, 2022) 1 Fianchi et al. Mediterr J Hematol Infect Dis. 2021; 13(1): e2021030; DOI: https://doi.org/10.4084/MJHID.2021.030 Any Grade and ≥ G3 DS in Phase 1a/b population 200 mg N =
Slide 12: Ziftomenib Demonstrates Encouraging Antileukemic Activity at 600 mg
ZIFTOMENIB DEMONSTRATES ENCOURAGING ANTILEUKEMIC ACTIVITY AT 600 MG Erba et al. ASH 2022 #64 (preliminary data as of October 24, 2022) 1 MRD was assessed for 5/7 CRc patients; 3 of those 5 patients (60%) tested were MRD negative CRc includes CR, CRh, CRi, CRp ORR includes CR, CRh, CRi, CRp, MLFS Bes
Slide 13: Decreasing Bone Marrow Blast Counts Consistently Reported
DECREASING BONE MARROW BLAST COUNTS CONSISTENTLY REPORTED Erba et al. ASH 2022 #64 (preliminary data as of October 24, 2022)
Slide 14: Clinical Activity of Ziftomenib Optimal at 600 mg Oral, Daily Dosing
CLINICAL ACTIVITY OF ZIFTOMENIB OPTIMAL AT 600 MG ORAL, DAILY DOSING Preliminary data as of October 24, 2022
Slide 15: Ziftomenib Induces Rapid and Extensive Differentiation of NPM1-Mutant Leukemia
ZIFTOMENIB INDUCES RAPID AND EXTENSIVE DIFFERENTIATION OF NPM1-MUTANT LEUKEMIA Baseline Bone Marrow Cellular BM (40%) with 75% blasts consistent with relapsed AML Cycle 1 Day 28 ziftomenib Hypercellular BM (>95%) with striking granulocytic hyperplasia and <1% blasts 61 yo male with NPM1-m, FLT3-ITD,
Slide 16: Evidence of Clinical Benefit in Patients with NPM1-Mutant AML
EVIDENCE OF CLINICAL BENEFIT IN PATIENTS WITH NPM1-MUTANT AML Preliminary data as of October 24, 2022 22 yo male with NPM1-m AML Baseline bone marrow blasts: 90% Prior therapies Cytarabine + idarubicin (7+3) Initiated ziftomenib at 600 mg DS during Cycle 1 (Gr2; non-serious) Non-cardiac chest and bo
Slide 17: Evidence of Clinical Benefit: Example of a KMT2A-Rearranged Non-Responding Patient
EVIDENCE OF CLINICAL BENEFIT: EXAMPLE OF A KMT2A-REARRANGED NON-RESPONDING PATIENT 47 yo female with KMT2A-r, TERT and BRAF AML Baseline bone marrow blasts: 52% Prior therapies ddAC + paclitaxel, CPX-35, SCT, Aza, FLAG Ida-ven, DLI, RT - gums Initiated ziftomenib at 200 mg DS during C1 Muscle and EM
Slide 18: Summary: KOMET-001 Phase 1 Clinical Trial of Ziftomenib
SUMMARY: KOMET-001 PHASE 1 CLINICAL TRIAL OF ZIFTOMENIB Ziftomenib demonstrates an encouraging safety profile and tolerability Reported events most often consistent with features and manifestations of underlying disease No evidence of drug-induced QTc prolongation Differentiation syndrome, an on-tar
Slide 19: Ziftomenib Clinical Development Path
DEVELOPMENT APPROACH STUDY STARTUP PHASE 1 REGISTRATION DIRECTED TRIAL MONOTHERAPY (Relapsed/refractory) COMBINATION WITH VENETOCLAX + AZACYTIDINE (Relapsed/refractory, frontline) COMBINATION WITH CYTARABINE + DAUNORUBICIN (7+3) (Frontline) COMBINATION WITH GILTERITINIB (Relapsed/refractory) COMBINA
Slide 20: Farnesyl Transferase Inhibitor Programs
FARNESYL TRANSFERASE INHIBITOR PROGRAMS
Slide 21: Evolution in the Therapeutic Applications of Farnesyl Transferase Inhibitors
Direct Inhibition of Oncogenic Proteins Overcoming Drug Resistance Preventing Emergence of Resistance Monotherapy activity in mutant tumors Overcome drug resistance to PI3Ka inhibitor in HNSCC Prevent emergence of resistance to EGFR inhibitor in NSCLC EVOLUTION IN THE THERAPEUTIC APPLICATIONS OF FAR
Slide 22: Tipifarnib Demonstrates Durable Anti-Tumor Activity in HRAS-Mutant HNSCC
ORR 55% N=20 evaluable patients Red, PR; blue, SD; green, not evaluable for efficacy; diamond, patient initiated treatment at 600 mg twice a day; cross, patient withdrew consent; arrow in bar, start of response; arrow, active treatment. Numbers at the end of the bars represent VAF for each patient.
Slide 23: AIM-HN: Registration-Directed Trial of Tipifarnib
Tipifarnib granted Breakthrough Therapy Designation for the treatment of patients with HRAS-mutant HNSCC based on data from RUN-HN study AIM-HN is a global, multi-center, registration-directed trial in patients with recurrent or metastatic HNSCC after one prior line of platinum therapy Evidence of m
Slide 24: Tipifarnib Has Potential to Overcome Resistance to PI3Kα Inhibitors in HNSCC
TIPIFARNIB HAS POTENTIAL TO OVERCOME RESISTANCE TO TREATMENT WITH PI3Kα INHIBITORS IN HNSCC The PI3K pathway is the most frequently activated pathway in HNSCC ~30% of tumors harbor PIK3CA mutation or amplification Feedback reactivation of PI3K –mTOR signaling drives innate resistance to PI3K inhibi
Slide 25: Combinations of Tipifarnib and PI3Kα Inhibitor Demonstrate Robust Activity in HNSCC PDX Models
COMBINATIONS OF TIPIFARNIB AND PI3Kα INHIBITOR DEMONSTRATE ROBUST ACTIVITY IN HNSCC PDX MODELS Malik et al. EORTC-NCI-AACR 2020 #159 Tipifarnib used at reduced dose to simulate potential lower doses in combination (80à60mg/kg BID) BYL-719 used at reduced dose to simulate potential lower doses in com
Slide 26: HRAS-MAPK and PI3K-mTOR Are Complementary Pathways in HNSCC
HRAS-MAPK and PI3K-mTOR are complementary pathways in HNSCC Overexpression of WT HRAS reported to induce resistance to PI3Kα inhibition HRAS is reported to preferentially activate PI3K (vs. KRAS; vs. MAPK) HRAS mutation/overexpression and PIK3CA mutations/amplifications account for up to 45% of HNSC
Slide 27: KURRENT-HN: Phase 1/2 Combination Trial of Tipifarnib and Alpelisib
Clinical collaboration to evaluate tipifarnib in combination with alpelisib for the treatment of patients with HNSCC whose tumors have HRAS overexpression and/or PIK3CA mutation and/or amplification Under the collaboration, Kura sponsors the trial and supplies tipifarnib and Novartis supplies alpeli
Slide 28: Durable Clinical Response Observed in Patient with PIK3Cα-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 PIK3Cα R88Q mutation (44%) and HRAS OE (3+ staining in 100% of tumor cells) by IHC from May 2021 biopsy DL1 tipifar
Slide 29: Tipifarnib Prevents Emergence of Resistance to Osimertinib In Vivo
Drug-tolerant cells (DTCs) arise within days of osimertinib exposure DTCs are characterized by Rho pathway activation RhoB, RhoE and LaminB are farnesylation-dependent proteins that are selectively upregulated in DTCs Genetic or pharmacologic inhibition of these targets kills DTCs and prevents the e
Slide 30: Tipifarnib Prevents Emergence of Resistance to Osimertinib In Vivo
Preclinical data generated through a collaboration with INSERM (the French National Institute of Health and Medical Research), suggest the potential to prevent emergence of resistance to EGFR inhibitor, osimertinib Figarol et al. AACR 2022 #7934 TIPIFARNIB PREVENTS EMERGENCE OF RESISTANCE TO OSIMERT
Slide 31: Tipifarnib Prevents Emergence of Resistance to Osimertinib In Vivo
TIPIFARNIB PREVENTS EMERGENCE OF RESISTANCE TO OSIMERTINIB IN VIVO Phase 1 clinical trial of tipifarnib and osimertinib in patients with treatment-naïve, locally advanced, or metastatic EGFR-Mutant NSCLC ORR = overall response rate; DOR – duration of response; PFS = progression-free survival
Slide 32: Next-Generation Farnesyl Transferase Inhibitor (FTI) KO-2806
NEXT-GENERATION FARNESYL TRANSFERASE INHIBITOR (FTI) KO-2806 nominated as development candidate for IND-enabling studies FTIs represent an attractive therapeutic target and commercial franchise in oncology with compelling opportunities in combination with other targeted therapies Goal is to develop
Slide 33: Forecasted Milestones & Financial Highlights
FORECASTED MILESTONES & FINANCIAL HIGHLIGHTS *Optimal biologically active dose **Unaudited, preliminary cash, cash equivalents and short-term investments as of 12/31/2022 PROGRAM MILESTONE ESTIMATED TIME OF ACHIEVEMENT ZIFTOMENIB (KO-539) Menin Inhibitor Dose first patient in Phase 2 registration-di
Slide 34: Developing Precision Medicines for the Treatment of Cancer
DEVELOPING PRECISION MEDICINES FOR THE TREATMENT OF CANCER Corporate Presentation – January 2023