Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — Q3 2024 Earnings Presentation
49 slides from Kura Oncology's earnings presentation, Nov 7, 2024
Slide 1: Developing Precision Medicines for the Treatment of Cancer
DEVELOPING PRECISION MEDICINES FOR THE TREATMENT OF CANCER Corporate Presentation – November 2024
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, KO-2806 and tipifarnib, plans regarding
Slide 3: Investment Highlights
Investment Highlights Targeted Advancing a pipeline of novel investigational therapies, forging new scientific and clinical paths to Oncology give patients a better chance for long-term, durable remissions Menin Inhibitor Programs – Ziftomenib & Next Generation • Potential to address up to 50% of ac
Slide 4: Experienced Leadership Team and Board of Directors
Experienced Leadership Team and Board of Directors Leadership Team Troy Wilson, Ph.D., J.D. Teresa Bair, J.D. Stephen Dale, M.D. Kathy Ford Brian Powl President & Chief Legal Officer Chief Medical Officer Chief Operating Officer Chief Commercial Officer Chief Executive Officer Pete De Spain Mollie L
Slide 5: Drug Candidate Pipeline
Drug Candidate Pipeline PROGRAM CLINICAL TRIAL STUDY STARTUP DOSE-ESCALATION DOSE-VALIDATION REGISTRATION DIRECTED ANTICIPATED MILESTONE NPM1-mutant acute myeloid leukemia (AML) Topline data in early 2025 KOMET-001 KMT2A-rearranged acute Now dosing patients Monotherapy lymphoblastic leukemia (ALL) N
Slide 6: Ziftomenib: Menin-KMT2A/MLL Inhibitor
ZIFTOMENIB: MENIN-KMT2A/MLL INHIBITOR
Slide 7: Ziftomenib Demonstrates Potential to Become a Cornerstone of AML Therapy
Ziftomenib Demonstrates Potential to Become a Cornerstone of AML Therapy Targets foundational mutations in up to 50% of AML cases • Compelling clinical data support frontline opportunity • Good tolerability profile, enabling continuous administration in combination with SOC • Combinations appear to
Slide 8: 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, BCL2, IDH1/2, DNMT3A) • KMT2A(MLL)-dependent genes contribute to
Slide 9: KOMET-001 Phase 1/2 Study of Ziftomenib in Relapsed / Refractory AML
KOMET-001 Phase 1/2 Study of Ziftomenib in Relapsed / Refractory AML Phase 1a Phase 1b Phase 1b Phase 2 Dose Escalation Validation Cohorts Expansion Registration-Enabling Completed Completed Completed (Ongoing) Enrollment Completed Expansion of 600 mg QD 50 mg Cohort 1: 200 mg QD 100 mg 1000 mg 600
Slide 10: Ziftomenib Demonstrates Optimal Pharmaceutical Properties
Ziftomenib Demonstrates Optimal Pharmaceutical Properties Clinical data from KOMET-001 demonstrate: • Ziftomenib demonstrates a dose-dependent increase in exposure up to RP2D at 600 mg • Ziftomenib is not a clinically meaningful CYP3A4 substrate • No dose adjustment of ziftomenib needed when adminis
Slide 11: Ziftomenib Demonstrates Encouraging Safety Profile in Phase 1
Ziftomenib Demonstrates Encouraging Safety Profile in Phase 1 • Differentiation syndrome (DS) appears manageable in NPM1-m monotherapy patients with mitigation strategy • 20% rate of mild to moderate DS • Rates of DS in KMT2A-r monotherapy patients were 42.9% at 200 mg and 38.9% at 600 mg; potential
Slide 12: Ziftomenib Has Highly Differentiated Monotherapy Activity
Ziftomenib Has Highly Differentiated Monotherapy Activity Best Overall Response 600 mg Differentiated CR Rates vs. SOC in 40% of NPM1 NPM1-m Phase 1a + 1b (n=20) Heavily Pretreated Patients patients CR 7 (35.0) achieved a CR during CR/CRh 7 (35.0) MUTATION CR % mDOR MEDIAN PRIORS course of CRc 8 (40
Slide 13: Case Studies Highlight Meaningful Durability and Favorable Tolerability
Case Studies Highlight Meaningful Durability and Favorable Tolerability 44 yo female with NPM1-m, DNMT3A and IKZF1 AML 7 Prior Tx Baseline bone marrow blasts: 14% Durable CR for 36 cycles on ziftomenib in 8th line including 2 HSCTs ziftomenib at 200 mg • CRmrd- after Cycle 1 Response • CRmrd- throug
Slide 14: Targeting the Menin-KMT2A Pathway has Potential to Benefit a Broader Subset of AML Patients
Targeting the Menin-KMT2A Pathway has Potential to Benefit a Broader Subset of AML Patients Ziftomenib has Demonstrated Evidence of Activity in Non-NPM1-m/Non-KMT2A-r Patients Off-Target Mutations: Best Change from • SETD2/RUNX1 patient achieved a Baseline in Bone Marrow Blasts – mITT Phase 1a CR at
Slide 15: 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
Slide 16: KOMET-007: Phase 1 Combination Trial of Ziftomenib in Patients with Newly Diagnosed or R/R AML
KOMET-007: Phase 1 Combination Trial of Ziftomenib in Patients with Newly Diagnosed or R/R AML Ziftomenib/cytarabine/daunorubicin (7+3) combination • Ziftomenib dosing begins on Cycle 1 Day 8 and is continuous thereafter • Cytarabine administered on Cycle 1 Day 1-7; administration of an additional c
Slide 17: KOMET-007: Phase 1 Combination Trial of Ziftomenib in Patients with Newly Diagnosed or R/R AML
KOMET-007: Phase 1 Combination Trial of Ziftomenib in Patients with Newly Diagnosed or R/R AML Ziftomenib/venetoclax/azacitidine combination • Ziftomenib dosing begins on Cycle 1 Day 8 and is continuous thereafter • Venetoclax administered per label in 28-day cycles with adjustments to cycle length
Slide 18: KOMET-007: Promising Safety and Tolerability Profile in Combination
KOMET-007: Promising Safety and Tolerability Profile in Combination Combinations mitigate risk of differentiation syndrome (DS) Grade ≥ 3 TEAEs (≥ 10%) n (%) Grade ≥ 3 Ziftomenib-Related AEs (All) n (%) Patients with Grade ≥ 3 TEAEs 18 (90) Patients with Grade ≥ 3 Ziftomenib-Related AEs 6 (30) Plate
Slide 19: 100% CR rate with Ziftomenib and 7+3 in 1L Patients with Adverse-Risk AML
100% CR rate with Ziftomenib and 7+3 in 1L Patients with Adverse-Risk AML* • Anticipated CR/CRi rate with 7+3 in all-comer 1L adverse risk patients: 32-33%1,2 1L Adverse-Risk Group CR Rate n=5 (n) Overall (NPM1-m + KMT2A-r) 100% (5) NPM1-m only (n=4) 100% (4) KMT2A-r only (n=1) 100% (1) • All patien
Slide 20: Ziftomenib + Ven/Aza with Pronounced Activity in Menin Inhibitor Naïve Patients
Ziftomenib + Ven/Aza with Pronounced Activity in Menin Inhibitor Naïve Patients • ~35-45% CR/CRi rate is expected in ven-naïve relapsed/refractory patients1 • Anticipated CR/CRi rate in KMT2A-r AML following two prior therapies <10%2 • 53% ORR in mITT population (n=15, including six menin experience
Slide 21: Ziftomenib + Ven/Aza Able to Drive Responses in Venetoclax Failures
Ziftomenib + Ven/Aza Able to Drive Responses in Venetoclax Failures • Expected response rates following ven/aza ~ 0-20%1-4 • Anticipated CR/CRi rate in KMT2A-r AML following two prior therapies < 10%5 Venetoclax Experienced Group ORR CR/CRi Rate CR/CRh Rate n=10 (n) (n) (n) Overall (NPM1-m + KMT2A-r
Slide 22: KOMET-008: Phase 1 Combination Trial of Ziftomenib in Patients with R/R AML
KOMET-008: Phase 1 Combination Trial of Ziftomenib in Patients with R/R AML Ziftomenib + gilteritinib combination • Phase 1a Dose Escalation • Arm A: Ziftomenib in combination with FLAG-IDA or LDAC or gilteritinib (illustrated above) in relapsed or refractory (R/R) NPM1-mutant AML • Arm B: Ziftomeni
Slide 23: Targeting Foundational Mutations has Transformed Deadly Hematologic Cancers into Chronic Diseases
Targeting Foundational Mutations has Transformed Deadly Hematologic Cancers into Chronic Diseases Multiple Myeloma • Until the 2000’s, there were few treatment options for multiple myeloma, and the median survival was 2–3 years • With the advent of immunomodulatory drugs (IMiDs) and proteasome inhib
Slide 24: Investigating Ziftomenib Across the AML Continuum in up to 50% of Patients
Investigating Ziftomenib Across the AML Continuum in up to 50% of Patients for Whom Menin-KMT2A Pathway is a Disease Driver 1L Treatable Relapsed / Refractory ~17K ~14K Prevalence of Ziftomenib Eligible Patients Post- IC or NIC Tx Targeted Tx if Non-Intensive FIT IC* or Transplant/ Transplant/ FLT3m
Slide 25: Ziftomenib: A Multi-Billion-Dollar Opportunity in AML and Beyond
Ziftomenib: A Multi-Billion-Dollar Opportunity in AML and Beyond Potential to Transform Outcomes Across the Continuum of Care • Initial approval would represent 30% of potential AML patients Relapsed / • KOMET-001 registration-directed study for FDA full approval Refractory • BTD granted in R/R NPM1
Slide 26: Ziftomenib in Gastrointestinal Stromal Tumors (GIST)
ZIFTOMENIB IN GASTROINTESTINAL STROMAL TUMORS (GIST)
Slide 27: GIST: A Unique Solid Tumor Opportunity for Ziftomenib
GIST: A Unique Solid Tumor Opportunity for Ziftomenib Advancing the treatment of TKI-resistant GIST Signaling pathways of KIT-mutated GIST1 • Ziftomenib-imatinib combination treatment showed robust antitumor activity in both imatinib-sensitive and imatinib- resistant GIST PDX models representing the
Slide 28: Ziftomenib-Imatinib Combination Displays Durable Antitumor Activity in First Line GIST PDX Model
Ziftomenib-Imatinib Combination Displays Durable Antitumor Activity in First Line GIST PDX Model The combination induces regressions in tumors that have relapsed following imatinib treatment • Imatinib monotherapy was tumoristatic, but the ziftomenib- imatinib combination induced deep regressions in
Slide 29: Ziftomenib and TKIs synergize in imatinib-resistant PDX models
Ziftomenib and TKIs synergize in imatinib-resistant PDX models Robust and durable responses seen in Ex13 GIST PDX model with combo GS11331, KIT Ex11 del and V654A vehicle • Both TKIs synergized with ziftomenib, 2500 dosing stopped ziftomenib inducing deep regressions in all animals, 2000 imatinib in
Slide 30: Ziftomenib and TKIs synergize in imatinib-resistant PDX models
Ziftomenib and TKIs synergize in imatinib-resistant PDX models Specific KIT mutation type does not seem to matter, with consistent imatinib- ziftomenib combo activity seen across different KIT mutant models Synthetic lethal activity in Imatinib resistant Ex17 GIST PDX models GS5106, KIT/K642E, Y822K
Slide 31: Opportunity for Menin Inhibitor in Diabetes
OPPORTUNITY FOR MENIN INHIBITOR IN DIABETES
Slide 32: Kura Menin Inhibitor Opportunity in Diabetes
Kura Menin Inhibitor Opportunity in Diabetes Unique combination of effects on both insulin deficiency and insulin resistance • Potential first-in-class regenerative medicine to restore β-cell mass • Prolonged activity observed for a month after dosing cessation • Selectivity for β-cells in islets of
Slide 33: Ziftomenib Reduces Blood Glucose and HbA1C Levels and Improves Insulin Sensitivity in ZDF Rat Model
Ziftomenib Reduces Blood4hGlucose and glucose fasting blood HbA1C Levels and Improves Insulin Sensitivity in ZDF Rat Model of Type 2 Diabetes 35 30 4h fasting blood glucose25 *** HOMA-IR BG (mM) 35 **** **** 500 20 **** Vehicle 30 400 Ziftomen 25 *** 15 **** Semaglu HOMA-IR BG (mM) **** **** 300 20
Slide 34: Ziftomenib Stimulates Insulin Production
Ziftomenib Stimulates Insulin Production Ziftomenib significantly increased serum insulin levels and serum c-peptide levels, indicating significant improvement to steady-state β-cell function 4h fasting Insulin c-peptide on Day27 HOMA-B 25 HOMA-B 5000 *** **** vehicl ns **** Vehicle 2500 c-peptide p
Slide 35: Ziftomenib Stimulates β-cell Proliferation in Human Pancreatic Islet Microtissues
Ziftomenib Stimulates -cell Proliferation with Minimal Effects on Non--cells in Human Pancreatic Islet Microtissues Ziftomenib stimulated the proliferation of -cells specifically in donor samples • Ziftomenib: 1x (nM) or 5x (nM) • Harmine: 10 µM (only used in STD, toxic under GTX) • Proliferating
Slide 36: KO-2806: Next-Gen Farnesyl Transferase Inhibitor
KO-2806: NEXT-GEN FARNESYL TRANSFERASE INHIBITOR
Slide 37: Therapeutic Applications of Farnesyl Transferase Inhibitors
Therapeutic Applications of Farnesyl Transferase Inhibitors • Dysregulated RAS-MAPK and PI3Ka/AKT/mTOR signaling are key drivers of various cancers. Targeted cancer therapies such as alpelisib and adagrasib slow tumor progression by inhibiting individual elements in this complex signaling pathway •
Slide 38: KO-2806 Potentiates the Antitumor Activity of Cabozantinib in ccRCC Models
KO-2806 Potentiates the Antitumor Activity of Cabozantinib in ccRCC Models The anti-angiogenic activity of cabozantinib is enhanced by addition of KO-2806 786-O CDX KI-12-0073 PDX Angiogenic markers in 786-O CDX tumors 1000 1200 Tumor volume (mm3) Tumor volume (mm3) 800 800 600 400 400 9.07 ± 0.11 8
Slide 39: Combination of KO-2806 Enhances the Antitumor Efficacy of a KRASG12C Inhibitor in NSCLC
Combination of KO-2806 Enhances the Antitumor Efficacy of a KRASG12C Inhibitor in NSCLC Combination of KO-2806 with adagrasib causes tumor regressions through suppression of mTOR signaling in KRASG12C NSCLC xenografts NCI-H2122 2500 (KRASG12C NSCLC) Vehicle Adagrasib KO-2806 Combo Vehicle 2000 p-ERK
Slide 40: Combination of KO-2806 Enhances the Depth and Duration of Response Compared to Adagrasib Alone
Combination of KO-2806 Enhances the Depth and Duration of Response Compared to Adagrasib Alone NCI-H2030 (KRASG12C NSCLC) 3000 stop dosing 100 Vehicle KO-2806 Adagrasib Combination 2500 mSD (6/8) mSD (7/8) mSD (0/8) (best response on treatment) Change in tumor volume (%) Tumor volume (mm3) mPR (0/8)
Slide 41: Tumors Progressing on Adagrasib are Re-Sensitized by the Addition of KO-2806
Tumors Progressing on the KRASG12C Inhibitor, Adagrasib, are Re- Sensitized by the Addition of KO-2806 Tumor regressions in the KO-2806 add-in group were comparable to the upfront combination of KO-2806 with adagrasib NCI-H2122 1000 (KRASG12C NSCLC) Change in tumor volume (%) 800 Tumor volume (mm3)
Slide 42: FIT-001 Phase 1 First-in-Human Clinical Trial of KO-2806 in Patients with Advanced Solid Tumors
FIT-001 Phase 1 First-in-Human Clinical Trial of KO-2806 in Patients with Advanced Solid Tumors PART 1A (MONOTHERAPY) PART 1A (COMBINATIONS) PART 1B (COMBINATIONS) DOSE ESCALATION DOSE ESCALATION DOSE EXPANSION OBJECTIVES Primary • Evaluate the safety and tolerability of KO-2806 (dose escalation) •
Slide 43: Tipifarnib: Farnesyl Transferase Inhibitor
TIPIFARNIB: FARNESYL TRANSFERASE INHIBITOR
Slide 44: Tipifarnib Shows Clinical Benefit in HRAS mutant HNSCC
Tipifarnib Shows Clinical Benefit in HRAS mutant HNSCC 1L 2L 3L+ Patients with High VAF in mITT (N=50) ORR by IRF: 7/24 ORR by IRF: 3/20 Investigator Independent 29% [0.13, 0.51] 15% [0.03, 0.38] Assessment Review Facility Best Overall Response, n (%) Confirmed CR 1 (2) 1 (2) Confirmed PR 14 (28) 9
Slide 45: KURRENT-HN: Phase 1/2 Combination Trial of Tipifarnib and Alpelisib in Patients with HNSCC
KURRENT-HN: PHASE 1/2 Combination Trial of Tipifarnib and Alpelisib in Patients with HNSCC Phase 1 clinical trial of tipifarnib and alpelisib in patients with recurrent/metastatic PIK3CA-amplified and/or PIK3CA-mutated HNSCC • Clinical collaboration to evaluate tipifarnib in combination with alpelis
Slide 46: 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
Slide 47: FTI Franchise Development Strategy
FTI Franchise Development Strategy Building on a strong KO-2806 in ccRCC and foundation with tipifarnib, KO- KRASG12C- 2806 and future FTIs are Tipifarnib in Mutant NSCLC (FIT-001) PIK3CA-dep positioned for near-term value HNSCC inflections, and could support (KURRENT-HN) Next-generation FTI to mult
Slide 48: Forecasted Milestones & Financial Highlights
Forecasted Milestones & Financial Highlights ESTIMATED TIME OF PROGRAM MILESTONE ACHIEVEMENT Present updated data from KOMET-007 trial in combination with ven/aza and 7+3 ASH 2024 Report topline results from KOMET-001 registration-directed trial in NPM1-mutant R/R AML Early 2025 ZIFTOMENIB Present p
Slide 49: Developing Precision Medicines for the Treatment of Cancer
DEVELOPING PRECISION MEDICINES FOR THE TREATMENT OF CANCER Corporate Presentation – November 2024