Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — Investor Presentation (January 2019)
40 slides from Kura Oncology's investor presentation, Jan 7, 2019
Slide 1: Corporate Presentation January 2019
Corporate Presentation January 2019 Developing Precision Medicines for the Treatment of Cancer 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 tipifarnib, KO-947 and KO-539, plans regarding regu
Slide 3: Investment Highlights
* Includes cash, cash equivalents and short-term investments Investment Highlights Targeted Oncology Advance pipeline of targeted drug candidates for selected solid tumors and hematologic malignancies Utilize precision medicine approaches; Fast-to-market potential Proprietary Pipeline Tipifarnib: Po
Slide 4: Advancing Pipeline of Targeted Drug Candidates
* Tipifarnib previously studied in > 5,000 patients in > 70 studies with a manageable safety profile as a single agent Note: Chemical structures of KO-947 and KO-539 not published Advancing Pipeline of Targeted Drug Candidates Tipifarnib KO-947 KO-539 Therapeutic Target Farnesyl transferase ERK kina
Slide 5: Biomarker Strategies May Unlock Clinical Activity and Commercial Value
Biomarker Strategies May Unlock Clinical Activity and Commercial Value Targeted Therapy Analytical Technologies Selected Patient Population Potential Value Enrichment of clinical activity Higher probability of success Expedited development and regulatory path Strong commercial case (next-generation
Slide 6: Multiple Clinical Proof-of-Concepts Reinforce Precision Medicine Approach
HRAS Mutant HNSCC HRAS Mutant Allele Frequency Clinical benefit observed in high frequency HRAS mutant population Multiple Clinical Proof-of-Concepts Reinforce Precision Medicine Approach CXCL12+ High CXCL12 Levels Clinical benefit observed in high CXCL12 AITL / PTCL population AITL/PTCL
Slide 7: Product Candidate Pipeline
Note: Given current focus in HRAS mutant and CXCL12 pathway indications, Phase 2 study in MDS has been deprioritized and is not currently enrolling new patients Investigator-Sponsored Trials | HRAS Mutant Urothelial Carcinomas, Samsung Medical Center | HRAS Mutant Lung Squamous Cell Carcinomas (LSCC
Slide 8: Tipifarnib in HRAS Mutant Solid Tumors
01 Tipifarnib in HRAS Mutant Solid Tumors KO-539 (Menin-MLL Inhibitor) 04 02 03 KO-947 (ERK Inhibitor) Tipifarnib Using CXCL12 Pathway Biomarkers
Slide 9: Tipifarnib is a Potent Inhibitor of HRAS Mutant Tumors
Tipifarnib is a Potent Inhibitor of HRAS Mutant Tumors Tumor Volume (mm3) Cetuximab 1mg Q4D Tipifarnib 80mg/kg BID Vehicle (Tipifarnib) Vehicle (Cetuximab) LU1513 HRAS Q61K (LSCC Model) Tipifarnib 80mg/kg BID Methotrexate 10mg/kg BIW Cetuximab 1mg QW Vehicle HN2606 HRAS G13R (HNSCC Model) Tumor Volu
Slide 10: Phase 2 Study of Tipifarnib: HNSCC Patients
Ho et al. European Society for Medical Oncology 2018 Congress #1046O | Preliminary results as of 9/7/18 * Response confirmed on 10/15/18 Phase 2 Study of Tipifarnib: HNSCC Patients (n=17 on study + 1 patient treated off protocol) Partial Response (n=6, +1 uPR off protocol) Stable Disease (n=4) Progr
Slide 11: Phase 2 Study of Tipifarnib: Other SCC Patients
Ho et al. European Society for Medical Oncology 2018 Congress #1046O | Preliminary results as of 9/7/18 Phase 2 Study of Tipifarnib: Other SCC Patients (n=6) Partial Response (n=1) Stable Disease (n=1) Progressive Disease Non Evaluable (n=2) Pending 1st Response Assessment (n=2) Baseline tumor HRAS
Slide 12: Association of HRAS Mutant Allele Frequency with Clinical Benefit
SD Non Evaluable PD Pending 1st Response Assessment 100 90 80 70 60 50 40 30 20 10 0 HRAS mutant AF (%, NGS) Ho et al. European Society for Medical Oncology 2018 Congress #1046 | Study KO-TIP-001 patients with HN and non-HN SCC tumors with available HRAS mutant allele data (10/17/18); one additional
Slide 13: Tipifarnib Development Program in HRAS Mutant HNSCC
RUN-HN KO-TIP-001 Phase 2 Proof-of-Concept Study SEQ-HN KO-TIP-007 Non-Interventional Screening & Outcomes Cohort AIM-HN KO-TIP-007 Registration-Directed Trial HRAS mutant patients who are not eligible for participation in AIM-HN may be referred to RUN-HN AIM-HN: Global, multi-center registration di
Slide 14: AIM-HN: Trial Design
Global, registration-directed trial Targeting ~ 100 clinical sites worldwide Anticipate ~ two years to enroll Primary endpoint: ORR by IRR Statistical assumptions At least 59 subjects, 80% power, 15% ORR (null hypothesis) and 30% ORR (response rate of interest) Minimum tumor HRAS mutant allele frequ
Slide 15: Activity When AIM-HN Criteria Applied Retrospectively
Ho et al. European Society for Medical Oncology 2018 Congress #1046 | Study KO-TIP-001 patients with HN and non-HN SCC tumors with available HRAS mutant allele data (10/17/18); one additional HNSCC patient was treated off protocol | * Allele frequency obtained post-ESMO | Pending analysis: 1 HNSCC p
Slide 16: HRAS Mutant Cancers: Market Opportunity
2,900-4,700 patients* HRAS Mutant HNSCC 1L 2L HNSCC Represents Significant Unmet Need1 Populations Based on Annual U.S. Incidence ORR 36% PFS 5.6 months OS ~10 months ORR 13-16% PFS ~2 months OS 6-8 months 1N Engl J Med. 2008 Sep 11;359(11):1116-27 | Keytruda & Opdivo package inserts | J Clin Oncol.
Slide 17: Tipifarnib Using CXCL12 Pathway Biomarkers
KO-539 (Menin-MLL Inhibitor) 04 02 01 03 KO-947 (ERK Inhibitor) Tipifarnib Using CXCL12 Pathway Biomarkers Tipifarnib in HRAS Mutant Solid Tumors
Slide 18: Key Characteristics of CXCL12
1 Burger et al. 2007. Br J Haematol. 137:288-96 | 2 Epstein 2004. Nat Rev Cancer 4:901-9 | 3 Feig et al. 2013. Proc Natl Acad Sci U S A. 110:20212-7 Key characteristics of CXCL12 Expressed primarily by immune cells, endothelial cells and stromal fibroblasts that constitute the tumor microenvironment
Slide 19: Tipifarnib is a Potent Inhibitor of CXCL12 Secretion by Stromal Cells
Primary CD1 mouse model of bone marrow cultures secrete abundant CXCL12 (SDF1, stroma derived factor 1) that was decreased by tipifarnib Research on specific farnesylated targets ongoing Witzig et al. ASH 2018 #2937; Kura Oncology Tipifarnib is a Potent Inhibitor of CXCL12 Secretion by Stromal Cells
Slide 20: Tipifarnib Using CXCL12 Pathway Biomarkers: PTCL / AITL
KO-539 (Menin-MLL Inhibitor) 04 02a 01 03 KO-947 (ERK Inhibitor) Tipifarnib Using CXCL12 Pathway Biomarkers: PTCL / AITL Tipifarnib in HRAS Mutant Solid Tumors
Slide 21: PTCL: CXCL12-Expressing Lymphoma with a Significant Unmet Need
1 Beleodaq® package insert 2 Istodax® package insert 3 Folotyn® package insert 4 1,000 mg/m2 administered over 30 mins by IV infusion once daily on days 1-5 of a 21-day cycle 5 14 mg/m2 administered over a 4-hour period by IV on days 1, 8 and 15 of a 28-day cycle 6 30 mg/m2 administered over 3-5 min
Slide 22: Clinical Activity in Phase 2 Study of Tipifarnib
Witzig et al. ASH 2018 #2937 | Preliminary data as of 11/21/18 | Missing measurement data from 2 subjects with best response of PD SPD: Sum of the products of diameters Clinical Activity in Phase 2 Study of Tipifarnib Change in SPD (%) AITL CXCL12 High PTCL PD SD PR CR
Slide 23: Association of High CXCL12 with Clinical Benefit in AITL/PTCL
The High CXCL12/CXCR4 subset of PTCL patients experienced 50% ORR and 90% clinical benefit with tipifarnib after a median of 3 prior therapies High CXCL12/CXCR4 expression ratio had 90% sensitivity and 93% specificity to identify PTCL patients likely to benefit from tipifarnib Witzig et al. ASH 2018
Slide 24: High CXCL12 Defines Poor Prognosis with Standard of Care in PTCL
Witzig et al. ASH 2018 #2937 A trend for worse prognosis was observed in PTCL patients with high CXCL12/CXCR4 expression ratio when treated with standard of care therapy Increasing levels of CXCL12 resulted in significantly more negative prognosis for SOC (not shown) CXCL12 high subset of patients r
Slide 25: Tipifarnib Using CXCL12 Pathway Biomarkers: Other Hematologic Malignancies
KO-539 (Menin-MLL Inhibitor) 04 02b 01 03 KO-947 (ERK Inhibitor) Tipifarnib Using CXCL12 Pathway Biomarkers: Other Hematologic Malignancies Tipifarnib in HRAS Mutant Solid Tumors
Slide 26: Association of High CXCL12 with Activity in Elderly Unfit AML
1 Blood. 2008 Mar 1;111(5):2589-96 | Expression data generated using microarray | HI: Hematologic Improvement CXCL12/CXCR4 Expression Ratio 1.4 0.4 0.3 0.2 0.1 0 Association of High CXCL12 with Activity of Tipifarnib in Elderly Unfit AML CR HI/SD PD/NE 7 CRs in 11 elderly unfit AML patients with hig
Slide 27: Opportunities in Other CXCL12-Expressing Hematologic Indications
Witzig et al. Blood. 2011 Nov 3;118(18):4882-9 Opportunities in Other CXCL12-Expressing Hematologic Indications Responses previously observed in patients with other relapsed/refractory hematologic tumors (unselected population) in NCI-sponsored Phase 2 trial of tipifarnib Disease Type n CR, n (%) PR
Slide 28: Tipifarnib Using CXCL12 Pathway Biomarkers: Solid Tumors
KO-539 (Menin-MLL Inhibitor) 04 02c 01 03 KO-947 (ERK Inhibitor) Tipifarnib Using CXCL12 Pathway Biomarkers: Solid Tumors Tipifarnib in HRAS Mutant Solid Tumors
Slide 29: Solid Tumors: Known Unmet Need in High CXCL12 Tumor Subsets
High CXCL12 expression consistently associated with reduced overall survival with standard of care in patients with pancreatic, esophagogastric and lung tumors1 1 Samarendra et al 2017. Br J Cancer 117, 124–135 Solid Tumors: Known Unmet Need in High CXCL12 Tumor Subsets
Slide 30: Potential CXCL12-Driven Tumor Indication in Pancreatic Cancer
2019 ASCO Gastrointestinal Cancers Symposium January 18, 2019 | San Francisco, CA Poster Session B: Cancers of the Pancreas, Small Bowel and Hepatobiliary Tract Abstract 275: Patient reported abdominal pain as a surrogate of the clinical benefit of tipifarnib in pancreatic cancer patients Authors: A
Slide 31: Cornerstone Proof-of-Concepts Support Expansion to Additional Indications
Cornerstone Proof-of-Concepts Support Expansion to Additional Indications Tipifarnib Farnesyl transferase (FT) inhibitor HRAS Mutant R/R HNSCC CXCL12+ R/R PTCL / AITL Other HRAS Mutant SCCs Earlier lines of therapy Other HRAS Mutant Solid Tumors Other CXCL12+ R/R B-cell Lymphomas Earlier lines of th
Slide 32: Biomarker Strategies Enlarge Patent Estate for Tipifarnib
U.S. patent 9,707,221 issued in July 2017 provides exclusivity for tipifarnib in HRAS mutant HNSCC indication to 2036 Corresponding patents beginning to issue in foreign countries U.S. patent 9,956,215 issued in May 2018 provides exclusivity for tipifarnib in certain CXCL12-expressing cancers to 203
Slide 33: KO-947 (ERK Inhibitor)
KO-539 (Menin-MLL Inhibitor) 04 03 01 02 Tipifarnib Using CXCL12 Pathway Biomarkers Tipifarnib in HRAS Mutant Solid Tumors KO-947 (ERK Inhibitor)
Slide 34: KO-947: Potent Inhibitor of ERK1/2
Summary Potent, selective small molecule inhibitor of ERK1/2 Demonstrates prolonged pathway modulation in preclinical tumor models Multiple tumors, including SCCs and KRAS mutant adenocarcinomas, identified as sensitive to KO-947 as monotherapy in preclinical models Mechanism-based and SOC combinati
Slide 35: KO-947 Demonstrates Robust Single-Agent Activity in Preclinical Studies
Burrows et al. AACR 2017 #5168/11 KO-947 Demonstrates Robust Single-Agent Activity in Preclinical Studies
Slide 36: KO-539 (Menin-MLL Inhibitor)
KO-947 (ERK Inhibitor) 03 04 01 02 Tipifarnib Using CXCL12 Pathway Biomarkers Tipifarnib in HRAS Mutant Solid Tumors KO-539 (Menin-MLL Inhibitor)
Slide 37: KO-539: Potent Inhibitor of Menin-MLL Interaction
Summary Potent, selective small molecule inhibitor of the menin-MLL interaction Robust antitumor activity observed in mixed lineage leukemias rearranged (MLL-r) as well as disseminated NPM1mut and DNMT3Amut AML PDX models Preliminary data suggests anti-leukemic activity by induction of myeloid diffe
Slide 38: KO-539 Produces Lasting Complete Remissions in AML Model
Last dose Vehicle KO-539 100 mg/kg QD Quizartinib 3 mg/kg QD Percent Survival Days of Therapy Burrows et al. AACR-NCI-EORTC 2017 LB-A27 CD45+ human AML blasts Overall survival Percent Circulating WBC Days of Therapy Tolerability Days of Therapy Bodyweight (g) KO-539 Produces Lasting Complete Remissi
Slide 39: Anticipated Milestones & Financial Highlights
* As of 3Q 2018 10-Q Anticipated Milestones & Financial Highlights Tipifarnib Farnesyl Transferase Inhibitor HRAS Mutant Indications CXCL12 Pathway Indications KO-539 Menin-MLL Inhibitor KO-947 ERK Inhibitor Phase 1 Status Milestones Program Initiation of registration-directed trial in HNSCC ü Addit
Slide 40: Developing Precision Medicines for the Treatment of Cancer
Corporate Presentation January 2019 Developing Precision Medicines for the Treatment of Cancer