Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — EHA 2023 Late-Breaking Presentation
14 slides from Kura Oncology's conference presentation, 2023
Slide 1: Activity, tolerability and resistance profile of the menin inhibitor ziftomenib in R/R NPM1-mutated AML
Activity, tolerability and resistance profile of the menin inhibitor ziftomenib in adults with relapsed or refractory NPM1-mutated AML Amir T. Fathi1, Eunice S. Wang2, Ghayas C. Issa3, Jessica K. Altman4, Pau Montesinos5, Stephane DeBotton6, Roland Walter7, Kristen Pettit8, Stephen Strickland9, Mrin
Slide 2: Disclosures
Disclosures Amir T. Fathi, MD • Consulting: Agios, Celgene/BMS, Astellas, Daiichi Sankyo, Takeda, Kura, Amgen, Pfizer, Seattle Genetics, AbbVie, and Genentech; Research support: Celgene/BMS and Agios 2
Slide 3: NPM1-Mutant AML is a Large Genetic Subset with a High Unmet Need
NPM1-Mutant AML is a Large Genetic Subset1 with a High Unmet Need NPM1-mutant AML ~30% ~6,000 new cases annually in the U.S.2 NPM1-m AML 5-year Overall Survival ~50%3 Adult patients with NPM1-mutant AML and select co-mutations and/or relapsed/refractory disease have a poor prognosis1 Median overall
Slide 4: Ziftomenib Targets the Menin-KMT2A Pathway, a Foundational Target in AML
Ziftomenib Targets the Menin-KMT2A Pathway, a Foundational Target in AML • NPM1-m and KMT2A-r drive overexpression of HOXA9/MEIS1 genes, critical for transformation to AML • KMT2A(MLL) sits upstream from major AML targets (i.e., FLT3, IDH1/2, DNMT3A) • KMT2A(MLL)-dependent genes contribute to therap
Slide 5: KOMET-001 Phase 1/2 Study of Ziftomenib in R/R AML
KOMET-001 Phase 1/2 Study of Ziftomenib in R/R AML Phase 1a Phase 1b Phase 1b Phase 2 Dose Escalation Validation Cohorts Expansion Registration-Enabling Completed Completed Completed (Ongoing) Ongoing Expansion of 600 mg QD 50 mg Cohort 1: 200 mg QD 100 mg 1000 mg 600 mg ~ ~ QD QD QD Cohort 2: 600 m
Slide 6: Baseline Patient Characteristics
Baseline Patient Characteristics Demographics 600 mg, n = 20 Disposition 600 mg, n = 20 Age, median (min, max), y 70.5 (22, 86) Patients in follow-up, n (%) 7 (35) Male, n (%) 6 (30) Reason for treatment discontinuation, n (%) ECOG PS 0, n (%) 3 (15) Adverse event (not study drug-related) 2 5 (25) P
Slide 7: Phase 1b Safety and Tolerability of Ziftomenib in R/R NPM1-m AML
Phase 1b Safety and Tolerability of Ziftomenib in R/R NPM1-m AML ≥ 20% Treatment-Emergent Adverse Events, n (%) NPM1-m, n = 20 ≥ 20% Treatment-Related Adverse Events, n (%) NPM1-m, n = 20 Patients with TEAEs (All Grades) 19 (95) Patients with TRAEs (All Grades) 12 (60) Diarrhea 9 (45) Nausea 4 (20)
Slide 8: Ziftomenib Demonstrates Encouraging Clinical Activity
Ziftomenib Demonstrates Encouraging Clinical Activity Mean Change in Platelets and ANC Best Overall Response n (%) for CRc up to C7D1 33% CR Complete remission rate (CR) 7 (35) co-FLT3m (N=6) CRc rate (CR+CRh+CRi) 8 (40) 50% CR co-IDHm Overall response rate (N=8) 9 (45) (CR+CRh+CRi+MLFS) CR 7 (35) C
Slide 9: Ziftomenib Monotherapy Drives Durable Responses
Ziftomenib Monotherapy Drives Durable Responses • Median DoR 8.2 months (95% CI: 1.0 to Not Evaluable) with a median follow up time of 8.8 months • Patient 1 remained on ziftomenib in CR (MRD-) into Cycle 36 • Patients 9 and 21 proceeded to HSCT • Patient 9 remains in complete response on ziftomenib
Slide 10: Ziftomenib Clears Measurable Residual Disease (MRD), Including Sub-Clones
Ziftomenib Clears Measurable Residual Disease (MRD), Including Sub-Clones Local MRD Analysis1 • 67% of patients (4 of 6) achieving CRc were MRD-negative2 Ongoing Central MRD Analysis, by NGS (Representative Patients)3 Subject 1: Prior Tx with NPM1 FLT3-TKD IDH1 Subject 2: Prior Tx with NPM1 FLT3-ITD
Slide 11: Ziftomenib Active Against Known Menin Gatekeeper Mutations
Ziftomenib Active Against Known Menin Gatekeeper Mutations • No major conformational changes observed in MeninT349M vs. wild-type (WT) protein • M327 and Y324 side chains adopt new conformations in MeninT349M but do not affect ziftomenib binding • Binding affinity of ziftomenib is reduced for MeninM
Slide 12: Ziftomenib Appears Less Susceptible to Mutations Associated with Resistance to Menin Inhibition
Ziftomenib Appears Less Susceptible to Observed Mutations Associated with Resistance to Menin Inhibition • Following reports of MEN1 resistance mutations with another menin inhibitor1, an analysis of KOMET-001 identified 1 of 29 subjects (3.4%) with the resistance mutation (MEN1-M327I) acquired whil
Slide 13: Conclusions
Conclusions • Ziftomenib demonstrates significant clinical activity with 45% ORR (35% CR rate) and lack of myelosuppression, with maintained count recovery in heavily pretreated R/R NPM1-m AML • Durable remissions with MRD clearance of foundational NPM1-m and other key co-mutations, including FLT3 I
Slide 14: Acknowledgements
Acknowledgements • The patients, their families, and caregivers • The study investigators and their study teams: • Centre Hospitalier Lyon-Sud • Hospital Universitario Virgen del • Northwestern University • CHU de Lille Rocío • Roswell Park • CHU de Nantes - Hôtel Dieu • Indiana University • UCLA •