Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — 24th Congress of the European Hematology Association (EHA) 2019
17 slides from Kura Oncology's conference presentation, 2019
Slide 1: Tipifarnib in Relapsed or Refractory AITL and CXCL12+ PTCL: Preliminary Results
Tipifarnib in Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma (AITL) and CXCL12+ Peripheral T-cell Lymphoma (PTCL): Preliminary Results from an Open-Label, Phase 2 Study Thomas Witzig1, Lubomir Sokol2, Won Seog Kim3, Francine Foss4, Eric Jacobsen5, Fatima de la Cruz Vicente6, Dolores Cabal
Slide 2: Disclosures
Disclosures • Consulting or Advisory Role – Celgene, Eisai, Mallinckrodt, miRagen, Seattle Genetics, Spectrum Pharmaceuticals, Verastem • Research Funding – Astex Pharmaceuticals, Daiichi Sankyo, Eisai, Kura Oncology, Kyowa Hakko Kirin, miRagen • Travel Support – Kura Oncology 24th Congress of the E
Slide 3: Tipifarnib is a CXCL12/CXCR4 Pathway Inhibitor
Tipifarnib is a CXCL12/CXCR4 Pathway Inhibitor • Key characteristics of CXCL12 – Expressed primarily by immune cells, endothelial cells and stromal fibroblasts that constitute the tumor microenvironment – CXCL12 and its receptors (CXCR4, CXCR7) are key factors linking cancer cells with the tumor mic
Slide 4: Study Design
Study Design1 Original Protocol: Stages 1 and 2 • R/R PTCL, ≥ 1 prior systemic therapy, measurable disease by Lugano Classification and/or mSWAT, ECOG 0-2 AITL Cohort (N=12) • Tipifarnib 600 - 900 mg orally (po) twice daily (bid) on days 1-7 • R/R AITL, ≥ 1 prior systemic therapy, measurable disease
Slide 5: Patient Demographics
Patient Demographics Stage 1/2 AITL Cohort wt CXCL12 3’UTR Cohort 1 Total Total Patients Treated, n (%) 19 (100) 2 16 (100) 15 (100) 50 (100) Total Evaluable for Efficacy 3, n (%) 18 (94.7) 2 11 (68.8) 12 (80.0) 41 (82.0) Histology AITL, n (%) 3 (15.8) 16 (100) 4 (26.7) 23 (46.0) PTCL-NOS, n (%) 14
Slide 6: Proof of Concept for Tipifarnib in wt CXCL12 3'UTR PTCL
Proof of Concept for Tipifarnib in wt CXCL12 3’UTR PTCL wt CXCL12 3’UTR Cohort: wt CXCL12 3’UTR Cohort: wt CXCL12 3’UTR Cohort: All pts AITL pts PTCL-NOS pts Total treated 15 4 11 Total efficacy evaluable 12 3 9 Overall Best Response Complete Response (CR) 3 2 1 Partial Response (PR) 2 - 2 Stable Di
Slide 7: Enrichment by wt CXCL12 3'UTR PTCL-NOS
Enrichment by wt CXCL12 3’UTR PTCL-NOS All PTCL-NOS All PTCL-NOS wt CXCL12 3’UTR1 Variant CXCL12 3’UTR2 Total treated 17 6 Total efficacy evaluable 15 6 Overall Best Response Complete Response (CR) 1 - Partial Response (PR) 2 - Stable Disease (SD) 10 - Progressive Disease (PD) 2 6 Not efficacy evalu
Slide 8: Tumor Reduction in PTCL-NOS, wt CXCL12 3'UTR
Tumor Reduction in PTCL-NOS, wt CXCL12 3’UTR • 77 yo male with PTCL-NOS Stage IV • CHOP x 5 with initial response then progression in skin • At baseline visit had multiple skin nodules biopsy proven relapsed PTCL • After two cycles of tipifarnib patient had near CR Baseline End of Cycle 2 24th Congr
Slide 9: Drivers of Tipifarnib's Activity in NOS
Drivers of Tipifarnib’s Activity in wt CXCL12 3’UTR NOS High CXCL12 in subjects with wt CXCL12 3’UTR, Overall low CXCL5 expression in NOS Genetics Mechanism of Action Activity High CXCL12 in subjects with wt CXCL12 3’UTR CXCL12 3’UTR 100000 CXCL12 RNA Seq Counts Reference (wt) Variant Tipifarnib dow
Slide 10: Proof of Concept for Tipifarnib in AITL
Proof of Concept for Tipifarnib in AITL AITL Cohort All AITL 1 Total treated 16 23 Total efficacy evaluable 11 17 Overall Best Response Complete Response (CR) 3 5 Partial Response (PR) 2 4 Stable Disease (SD) 3 3 Progressive Disease (PD) 3 5 Not efficacy evaluable (NE) 5 6 PPS2 mITT PPS2 mITT Overal
Slide 11: AITL: Durable clinical responses and subsequent transplant
AITL: Tipifarnib treatment resulted in durable clinical responses and enabled subsequent transplant in patients achieving a CR Maximum Change in Tumor Burden Time on Treatment 40 20 % Change in SPD 0 -20 -40 Allo BMT Median 5.5 months (95% CI 3.7-30.6) -60 Allo BMT for AITL patients with SD/PR/CR -8
Slide 12: Tipifarnib is Active in High CXCL12 Expressing AITL and PTCL NOS Tumors
Tipifarnib is Active in High CXCL12 Expressing AITL and PTCL NOS Tumors sample HISTOL RESP CXCL12/CXCR4 6 AITL PR 7.42 Maximum Change in Tumor Burden 28 AITL CR 2.4 34 AITL PD/NE 1.5 36 NOS SD 1.3 40 17 NOS SD 0.85 Tipifarnib targets 32 AITL PD/NE 0.8 37 NOS SD 0.6 CXCL12 and is active in 20 1 AITL
Slide 13: High Activity of Tipifarnib in AITL with KIR3DL2 mutations
High Activity of Tipifarnib in AITL with KIR3DL2 mutations Best Response to Tipifarnib (N=16 AITL with sequenced tumors) • CXCL12 and CXCL5 drive, respectively, KIR3DL2 Mutant KIR3DL2 Wild Type sensitivity and resistance to tipifarnib. N 8 8 • AITL expresses high levels of CXCL12 and Overall Best Re
Slide 14: Drivers of Tipifarnib's Activity in AITL
Drivers of Tipifarnib’s Activity in AITL Overall high CXCL12 expression in AITL, Low CXCL5 expression in KIR3DL2 mutant AITL Genetics Mechanism of Action Activity High CXCL12 expression in AITL histology Tipifarnib downregulates CXCL12 secretion Histology 100000 CXCL12 RNA Seq Counts AITL DMSO Tipif
Slide 15: Safety and tolerability of tipifarnib in PTCL
Safety and tolerability of tipifarnib in PTCL • All patients (N = 48)1 had at least one treatment-emergent adverse event (TEAE); 42 (88%) had at least 1 study drug-related TEAE and 13 (27%) had at least 1 study drug-related SAE. One study drug related death (lung infection) has been reported. • TEAE
Slide 16: Conclusions
Conclusions • The AITL and wt CXCL12 3’UTR cohorts met pre-specified statistical hypotheses supporting proof-of-concept for tipifarnib in PTCL. • Tipifarnib is active in AITL pts and in PTCL-NOS pts with wt CXCL12 3’UTR – AITL: 53% ORR (all subjects, PPS) – PTCL-NOS with wt CXCL12 3’UTR: 20% ORR (al
Slide 17: Acknowledgements
Acknowledgements • Patients, their families and caregivers • Study Investigators and their study teams • Kura Oncology 24th Congress of the European Hematology Association, Abstract S869 17
Kura Oncology — 24th Congress of the European Hematology Association (EHA) 2019 on 6ix