Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — ASH 2022
18 slides from Kura Oncology's conference presentation, November 2022
Slide 1: Update on a Phase 1/2 First-in-Human Study of Ziftomenib in R/R AML
Update on a Phase 1/2 First-in-Human Study of the Menin- KMT2A (MLL) Inhibitor Ziftomenib (KO-539) in Patients with Relapsed or Refractory Acute Myeloid Leukemia Harry P. Erba1, Amir Fathi2, Ghayas Issa3, Jessica Altman4, Pau Montesinos 5, Mrinal Patnaik6, James Foran7, Stephane DeBotton8, Maria Bae
Slide 2: NPM1-m and KMT2A(MLL)-r AML Represent a Significant Unmet Need
NPM1-m and KMT2A(MLL)-r AML Represent a Significant Unmet Need No FDA-Approved Targeted Therapies Exist Today NPM1-mutant AML KMT2A-rearranged AML ~30% ~6,000 new cases annually in U.S. 1 ~5-10% ~1,000-2,000 new cases annually in U.S. 1 AML AML Adult patients with NPM1-m and select co-mutations Adul
Slide 3: KOMET-001 Phase 1a Clinical Trial of Ziftomenib in R/R AML
KOMET-001 Phase 1a Clinical Trial of Ziftomenib in Patients with Relapsed or Refractory (R/R) AML Phase 1a Phase 1b Phase 1b Dose Escalation Validation Cohorts Expansion Cohort 1: 200 mg Expansion of 600 mg 50 mg 100 mg ~~ 1000 mg Cohort 2: 600 mg OBJECTIVES Dose escalation in all-comer patients Enr
Slide 4: Phase 1a Dose Escalation – Demographics
Phase 1a Dose Escalation – Demographics All Patients Demographics (N = 30) Median age - n (Min, Max) 65.5 (22, 85) Male – n (%) 17 (56.7) ECOG PS 1 – n (%) 19 (63.3) ECOG PS 2 – n (%) 6 (20.0) KMT2A-r – n (%) 10 (33.3) NPM1-m – n (%) 4 (13.3) Non KMT2A-r/NPM1-m – n (%) 16 (53.3) Median no. of prior
Slide 5: Phase 1a Dose Escalation – Safety
Phase 1a Dose Escalation – Safety ≥Gr3 TEAEs 50 mg 100 mg 200 mg 400 mg 600 mg 800 mg 1000 mg (All Causality) (N = 1) (N = 1) (N = 6) (N = 5) (N = 5) (N = 11) (N = 1) Preferred Term n (% ) n (% ) n (% ) n (% ) n (% ) n (% ) n (% ) Anemia 0 0 2 (33.3) 1 (20.0) 3 (60.0) 2 (18.2) 0 Pneumonia 1 (100.0)
Slide 6: Ziftomenib Demonstrates Encouraging Early Clinical Activity in the Phase 1a, All Comer Population
Ziftomenib Demonstrates Encouraging Early Clinical Activity in the Phase 1a, All Comer Population KMT2A-r NPM1-m SETD2, RUNX1 Other Genetic Subtypes 24-Oct-2022 Data Cut
Slide 7: KOMET-001 Phase 1b Clinical Trial of Ziftomenib in R/R AML
KOMET-001 Phase 1b Clinical Trial of Ziftomenib in Patients with Relapsed or Refractory (R/R) AML Phase 1a Phase 1b Phase 1b Dose Escalation Validation Cohorts Expansion Cohort 1: 200 mg Expansion of 600 mg 50 mg 100 mg ~~ 1000 mg Cohort 2: 600 mg OBJECTIVES Dose escalation in all-comer patients Enr
Slide 8: Phase 1b Baseline Characteristics, Demographics, and Disposition
Phase 1b Baseline Characteristics, Demographics, and Disposition 200 mg 600 mg 200 mg 600 mg Demographics Disposition (N = 17) (N = 36) (N = 17) n (% ) (N = 36) n (% ) Median age - n (Min, 49.0 54.5 Patients on Treatment 0 10 (27.8) Max) (30, 79) (18, 86) Patients in Follow-Up 1 (5.9) 17 (47.2) Male
Slide 9: 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 200 mg 600 mg (Regardless of Causal Assessment) 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) 2
Slide 10: Characterization of Differentiation Syndrome (DS) with Ziftomenib
Characterization of Differentiation Syndrome (DS) with Ziftomenib Any Grade and ≥G3 DS in P1a/b population † Ziftomenib Accumulates in Tissues in Mice 200 mg 600 mg N = 17, n (%) N = 36, n (%) 160000 NPM1-m (all grades) 0/4 (0) 4/20 (20.0) Concentration (ng/mL) or (ng/g) 140000 ≥ Gr3 0/4 (0) 1/20 (5
Slide 11: Ziftomenib Demonstrates Encouraging Antileukemic Activity at 600 mg
Ziftomenib Demonstrates Encouraging Antileukemic Activity at 600 mg Best Overall Response 200 mg 600 mg • 2 pts had concurrent IDH1/2 NPM1-m Phase 1a + 1b (n=6) (n=20) • 2 pts had both IDH1/2 and FLT3-ITD/TKD CR 1 (16.7) 6 (30.0) CR/CRh 1 (16.7) 6 (30.0) CRc 1 (16.7) 7 (35.0) Of IDH1/2 co-mutants (7
Slide 12: Decreasing Bone Marrow Blast Counts Consistently Reported
Decreasing Bone Marrow Blast Counts Consistently Reported 24-Oct-2022 Data Cut
Slide 13: Ziftomenib Causes Differentiation of NPM1-mutant Leukemia
Ziftomenib Causes Differentiation of NPM1-mutant Leukemia Baseline Bone Marrow Case Example: 61 yo male with NPM 1-m, FLT3- Cellular BM (40%) with ITD, and IDH2 AML 75% blasts consistent Baseline bone marrow blasts: 75% with relapsed AML 7+3, Midostaurin, HiDAC, Prior therapies gilteritinib Initiate
Slide 14: Clinical Benefit: An Example of a KMT2A-r Non-Responder
Clinical Benefit: An Example of a KMT2A-r Non-Responder Baseline After 2 cycles Case Example: 47 yo female with KM T2A-r, TERT, and BRAF AML Baseline bone marrow blasts: 52% ddAC + paclitaxel, CPX-35, SCT, Aza, Prior therapies FLAG Ida-ven, DLI, RT - gums Initiated ziftomenib at 200 mg Muscle and EM
Slide 15: Pharmacokinetic/Pharmacodynamic Analyses Support 600 mg Dosing
Pharmacokinetic/Pharmacodynamic Analyses Support 600 mg Dosing • Dose-dependent increases in exposure support 600 mg vs 200 mg dose MEIS1 C1D28 1 (relative to baseline) Log2 Fold Change 0 200 600 -1 -2 -3 Dose, mg • MEIS1 expression at C1D28 was 6-fold lower in patients dosed at 600 mg vs 200 mg – H
Slide 16: Ziftomenib 600 mg Demonstrates Optimal Clinical Benefit
Ziftomenib 600 mg Demonstrates Optimal Clinical Benefit KMT2A-r NPM1-m 24-Oct-2022 Data Cut
Slide 17: Acknowledgements
Acknowledgements • The patients, their families, and caregivers • The study investigators and their study teams • The study is sponsored by Kura Oncology, Inc.
Slide 18: Conclusions
Conclusions 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-target effect, manageable with mitigation