Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — Investor Presentation (December 2020)
34 slides from Kura Oncology's investor presentation, Dec 7, 2020
Slide 1: Developing Precision Medicines for the Treatment of Cancer
DEVELOPING PRECISION MEDICINES FOR THE TREATMENT OF CANCER Corporate Presentation – December 2020 Exhibit 99.1
Slide 2: 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 tipifarnib and KO-539, plans regarding regulatory filings, our expectations re
Slide 3: Investment Highlights
*Cash, cash equivalents and short-term investments as of September 30, 2020 Targeted Oncology Advancing two wholly owned, targeted oncology drug candidates using a precision medicine approach; fast-to-market strategy Proprietary Pipeline Tipifarnib: Farnesyl transferase inhibitor Registration-direct
Slide 4: Kura Leadership Team and Board of Directors
Proven oncology drug development and commercialization expertise Kura Leadership Team and Board of Directors Leadership Team Troy Wilson, Ph.D., J.D. President & Chief Executive Officer James Basta, J.D. Chief Legal Officer Stephen Dale, M.D. Chief Medical Officer Kirsten Flowers Chief Commercial Of
Slide 5: Advancing Targeted Oncology Drug Candidates Using a Precision Medicine Approach
Advancing Targeted Oncology Drug Candidates Using a Precision Medicine Approach Targeting KMT2A(MLL)-r and NPM1-Mutant AML Orphan Drug Designation Opportunity to address large patient population with high unmet need in relapsed/refractory AML Publications support potential to drive robust and persis
Slide 6: Tipifarnib in HRAS Mutant Solid Tumors
TIPIFARNIB IN HRAS MUTANT SOLID TUMORS
Slide 7: Tipifarnib in HRAS Mutant Solid Tumors
Tipifarnib in HRAS Mutant Solid Tumors Unique MOA targets farnesylation, an essential modification required for activity of the HRAS mutant oncoprotein Phase 2 data demonstrates treatment response of ~ 50% ORR, ~ 6 months PFS and ~ 15 months OS in advanced recurrent and metastatic HRAS mutant HNSCC
Slide 8: Tipifarnib Inhibits Farnesylation – An Essential Modification Required for HRAS Activity
Cell membrane HRAS HRAS FTase HRAS FTase Tipifarnib HRAS (mutant) HRAS (wild-type) Tipifarnib inhibits farnesylation and signaling activity of the HRAS oncoprotein Farnesylation is essential for HRAS signal transduction activity HRAS mutations drive proliferation and resistance mechanisms in solid t
Slide 9: Tipifarnib Displays Robust, Selective Activity in HRAS Mutant HNSCC Models
Source: Kura internal data Tipifarnib Tipifarnib Vehicle Vehicle Change in tumor volume (%)* HRAS wild type HRAS-mutant * Capped at 200%. Actual values 208-597% MAPK signaling Cell cycle arrest Apoptosis Angiogenesis Squamous differentiation Antitumor activity in PDX models HRAS membrane displacemen
Slide 10: Durable Anti-Tumor Activity with Tipifarnib as a Monotherapy in HRAS Mutant HNSCC
Ho et al. AACR-NCI-EORTC 2019 #384 (preliminary data as of 10/17/19) Efficacy-evaluable patients with HRAS mutant variant allele frequency (VAF) ≥ 20% and serum albumin ≥ 3.5 g/dL, or HRAS VAF ≥ 35% One patient treated off-protocol through compassionate use RUN-HN: Phase 2 Trial in HRAS Mutant HNSCC
Slide 11: RUN-HN: Progression-Free Survival in HRAS Mutant HNSCC
Ho et al. ASCO 2020 #6504 (preliminary data as of 9/30/19) Efficacy-evaluable patients with HRAS mutant variant allele frequency (VAF) ≥ 20% and serum albumin ≥ 3.5 g/dL, or HRAS VAF ≥ 35% One patient treated off-protocol through compassionate use Progression-Free Survival with Tipifarnib and Last P
Slide 12: Overall Survival in Patients with HRAS Mutant HNSCC
Overall Survival in Patients with HRAS Mutant HNSCC Median OS (months) 95% CI Lower Upper HNSCC with high VAF, including additional patient (N=18) 15.4 7.0 46.4 Ho et al. ASCO 2020 #6504 (preliminary exploratory data as of 9/30/19) Efficacy-evaluable patients with HRAS mutant variant allele frequenc
Slide 13: Registration Strategy in HRAS Mutant HNSCC
* Feedback from end-of-Phase 2 meeting with FDA 2018 AIM-HN: Registration-directed trial of tipifarnib in HRAS mutant HNSCC Recurrent or metastatic patients after one prior line of platinum therapy Now open in ~90 clinical sites in the U.S., Europe and Asia Amended trial to enroll all HRAS mutant HN
Slide 14: Tipifarnib Has the Potential to be the First Small Molecule Targeted Therapy for HNSCC Patients
Only ~1/3 of patients with advanced diagnosis survive 5 years4 SURVIVORS DO NOT SURVIVE 0 20 40 60 80 100 Outcomes with currently available therapies (including I-O therapy) are poor5 1 Bray et al. CA Cancer J Clin. 2018;68(6):394-424 2 Cramer et al. Nat Rev Clin Oncol. 2019 Nov;16(11):669-683 | ACS
Slide 15: Expansion Opportunities for Tipifarnib in HRAS and PI3Kα Dependent HNSCC
Expansion Opportunities for Tipifarnib in HRAS and pi3kα dependent HNSCC
Slide 16: HRAS Dependent Tumors Represent a Significant Subset of HNSCC
HRAS Dependent Tumors Represent a Significant Subset of HNSCC with Distinct Biology Several independent studies cluster HRAS mutant HNSCCs as part of a larger subset1 TCGA cohort shows overexpression of HRAS gene in 25-30% of HNSCC2 Average HRAS expression in HNSCC is 5-10x higher than in other tumo
Slide 17: HRAS is a Central Resistance Mechanism to Other Therapies in PDX Models
HRAS is a Central Resistance Mechanism to Other Therapies in PDX Models of HRAS Dependent HNSCC Tipifarnib displays additive or synergistic anti-tumor activity with a range of other drugs in HRAS-overexpressing patient-derived xenograft (PDX) models HRAS represents a key node at the center of HNSCC
Slide 18: 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 19: Combinations of Tipifarnib and PI3Kα Inhibitors Have Broad Therapeutic Potential in HNSCC
Combinations of Tipifarnib and PI3Kα inhibitors Have Broad Therapeutic Potential 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
Slide 20: Layered Patent Strategy Provides Patent Exclusivity to 2036
Patents cover combinations of tipifarnib with other agents (e.g., I/O) Additional patents possible with specific agents, doses, schedules, etc. Multiple issued U.S. patents covering biomarker-guided indications provide patent exclusivity to 2036 Additional patent applications pending in the U.S. and
Slide 21: KO-539: Menin Inhibitor in Acute Leukemias
KO-539: Menin Inhibitor in acute leukemias
Slide 22: KO-539: Menin Inhibitor
KO-539: Menin Inhibitor Potent, selective, reversible, oral inhibitor of menin-KMT2A(MLL) protein-protein interaction for treatment of AML Novel MOA targeting epigenetic dysregulation leading to differentiation block and anti-tumor activity in 35% or more of AML Preliminary data from KOMET-001 Phase
Slide 23: Targeting Menin-KMT2A(MLL) Interaction in Two Genetic Subsets of AML
Targeting Menin-KMT2A(MLL) Interaction Provides Potential Therapeutic Intervention into Two Genetic Subsets of AML Targeting the menin-KMT2A(MLL) interaction to reverse epigenetic dysregulation in MLL-rearranged AML A central role for menin-KMT2A(MLL) interaction in epigenetic dysregulation in NPM1-
Slide 24: KO-539 Produces Lasting Complete Remissions in an AML Model
Burrows et al. AACR-NCI-EORTC 2017 LB-A27 100% (10/10) of animals treated with single-agent KO-539 cleared their leukemia and became long-term survivors Tumor growth inhibition was durable – no leukemia was detectable in blood or bone marrow two months after cessation of dosing KO-539 was well toler
Slide 25: KOMET-001: Phase 1/2A First-in-Human Study of KO-539 in R/R AML
KOMET-001: Phase 1/2A First-in-Human Study of KO-539 in Patients with Relapsed or Refractory AML KOMET: Kura Oncology Menin-MLL Trial MLL/KMT2A-rearranged AML Cohort NPM1-mutant AML Cohort Determine recommended Phase 2 dose and/or MTD Safety and tolerability Pharmacokinetics Early evidence of antitu
Slide 26: Continuous Daily Dosing of KO-539 Has Been Well-Tolerated
Continuous Daily Dosing of KO-539 Has Been Well-Tolerated with a Manageable Safety Profile No dose discontinuations due to treatment-related adverse events (AEs) No evidence of QT prolongation or other clinically significant ECG changes Treatment-related AEs (N=12) Grade ≥ 3 (all) Grade 1,2 (≥ 10%)
Slide 27: KO-539 Demonstrates Encouraging Early Clinical Activity
KO-539 Demonstrates Encouraging Early Clinical Activity Wang et al. ASH 2020 #115 (preliminary data as of November 2, 2020) KOMET-001 (n=12) Dose Mutational Profile CYP3A Inhibitor # of Prior Regimens Clinical Activity 400 mg RUNX1, SRSF2, ASXL1, TET2, STAG2, BCOR, PTPN11 Yes 3 Decreased peripheral
Slide 28: Case Study – SETD2, RUNX1 Mutant AML
Case Study – Patient #2 2 prior lines of therapy KO-539 ~ 5 months C1D28 SD C3D28 CR, MRD+ C6D28 PR C8D28 PD Patient Characteristics Demographics 69-year-old male Mutational profile SETD2, RUNX1 Prior lines of therapies 2 (decitabine; CD33/CD3 bispecific antibody) KO-539 dose 100 mg, escalated to 20
Slide 29: Case Study – NPM1, DNMT3A, KMT2D, FLT3-TKD Mutant AML
Case Study – Patient #3 7 prior lines of therapy KO-539 3 years and ~ 7 months C1D28 CR, MRD- C3D28 CR, MRD- Patient Characteristics Demographics 44-year-old female Mutational profile NPM1, DNMT3A, KMT2D, FLT3-TKD Prior lines of therapies 7 (incl. decitabine+venetoclax, gilteritinib, itacitinib, flu
Slide 30: Summary of Preliminary Data from KOMET-001
Summary of Preliminary Data from KOMET-001 KO-539 is a potent and selective inhibitor of the menin-KMT2A/MLL complex KO-539 has been well tolerated with a manageable safety profile to date Observed toxicities appear to be reversible and manageable No evidence of QTc prolongation KO-539 demonstrates
Slide 31: Multiple Expansion Opportunities in Acute Leukemias
Multiple Expansion Opportunities in Acute Leukemias Maximum Tolerated Dose and/or Recommended Phase 2 Dose Anticipated Q1 2021 Expansion Cohorts: 1) KMT2A(MLL)-r AML and 2) NPM1-mutant AML Potential 3rd AML Expansion Cohort: Other Genetics Pediatric Development Earlier Lines of Therapy in AML Combin
Slide 32: Relapsed/Refractory AML is a Challenging Disease Associated with Poor Outcomes
Relapsed/Refractory AML is a Challenging Disease Associated with Poor Outcomes Estimated 1,000-2,000 new cases in the U.S. per year7 (5-10% of AML) NCCN guidelines denote that MLL-r confers poor prognosis9 Estimated 6,000 new cases in the U.S. per year7 (~30% of AML) Known co-mutations confer worse
Slide 33: Investment Highlights
*Cash, cash equivalents and short-term investments as of September 30, 2020 Targeted Oncology Advancing two wholly owned, targeted oncology drug candidates using a precision medicine approach; fast-to-market strategy Proprietary Pipeline Tipifarnib: Farnesyl transferase inhibitor Registration-direct
Slide 34: Developing Precision Medicines for the Treatment of Cancer
DEVELOPING PRECISION MEDICINES FOR THE TREATMENT OF CANCER Corporate Presentation – December 2020
Kura Oncology — Investor Presentation (December 2020) on 6ix