Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — Technical Presentation (December 2019)
21 slides from Kura Oncology's technical presentation, Dec 8, 2019
Slide 1: Proof of Concept for Tipifarnib in Relapsed or Refractory AITL and CXCL12+ PTCL
Proof of Concept for 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 E. Witzig1, Lubomir Sokol2, Francine M. Foss3, Won-Seog Kim4, Eric Jacobsen5, Maria de Fati
Slide 2: Tipifarnib is a Farnesyltransferase (FT) Inhibitor
Tipifarnib is a Farnesyltransferase (FT) Inhibitor • FT adds a 15 Carbon farnesyl group to proteins with CaaX motif • C = cysteine; A = aliphatic a.a. X= determines which enzyme does the prenylation • Tipifarnib is an oral FTI that has been tested in >5000 unselected patients with a variety of solid
Slide 3: ORR in all 93 patients with different types of lymphoma = 20%
Blood 2011 10.1182/blood-2011-02-334870 Blood 2011 10.1182/blood-2011-02-334904 ORR in all 93 patients with different types of lymphoma = 20% NCT00082888; LS038B Iowa/Mayo SPORE trial 61st ASH Annual Meeting & Exposition, Abstract 468 4
Slide 4: Development Path
Development Path • Studies in unselected patients with NHL, AML and solid tumors were not felt to be promising enough for registration – Drug development of Tipi and other FTI was halted • Drug in licensed to Kura Oncology from Janssen • Samples from previous studies were re-evaluated for new biomar
Slide 5: Goals of this Presentation
Goals of this Presentation • To review data from this new ongoing phase 2 study (KO-TIP- 002) of single-agent tipifarnib in T-cell lymphoma – Single-agent tipifarnib at a dose of 300 mg po bid days 1-21 q28 days • Demonstrate how 3 biomarkers learned from unselected pts are being used prospectively
Slide 6: CXCL12 expression and its receptor CXCR4; CXCL5 expression and its receptor CXCR2
CXCL12 expression and its receptor CXCR4 CXCL5 expression and its receptor CXCR2 10.1016/j.ejpb.2017.07.003 10.1038/s41467-019-12108-6 61st ASH Annual Meeting & Exposition, Abstract 468 7
Slide 7: Tipifarnib is a CXCL12/CXCR4 Pathway Inhibitor
Tipifarnib is a CXCL12/CXCR4 Pathway Inhibitor • High CXCL12 expression defines poor prognosis in PTCL – 50% of AITL and 35% of PTCL-NOS have high CXCL12 expression – Trend for worse prognosis in AITL and PTCL-NOS patients with tumors with high CXCL12 expression1 • Tipifarnib is a CXCL12/CXCR4 pathw
Slide 8: Study Design of KO-TIP-002
Study Design of KO-TIP-0021 Protocol Stages 1 and 2 • Unselected R/R PTCL, including AITL and PTCL-NOS • Tipifarnib 600 - 900 mg orally (po) twice daily (bid) on days 1-7 and days 15-21 every 28 days AITL Cohort (N = up to 20) • R/R AITL, ≥ 1 prior therapy, measurable disease, ECOG 0-2 • Results2: P
Slide 9: 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: Variant CXCL12 3’UTR2 PTCL-NOS PTCL-NOS enrolled in S1/2 Total treated 11 6 Total efficacy evaluable 9 6 Overall Best Response Complete Response (CR) 1 - Partial Response (PR) 2 - Stable Disease (SD) 6 - Progressive Dise
Slide 10: Tumor Reduction in PTCL-NOS, wt CXCL12 3'UTR
Tumor Reduction in PTCL-NOS, wt CXCL12 3’UTR • 77 yo; PTCL-NOS Stage IV • CHOP x 5 with response then PROG biopsy-proven PTCL relapse in multiple skin nodules • Rapid PR after two cycles of tipifarnib Baseline End of Cycle 2 61st ASH Annual Meeting & Exposition, Abstract 468 11
Slide 11: Demographics: All AITL Patients
Demographics: All AITL Patients1 Total AITL Patients Treated1, n (%) 26 (100) AITL Patients Evaluable for Efficacy 2, n (%) 20 (100) Age, yrs Median 66.3 Min, Max 46, 87 Male, n (%) 17 (65) Female, n (%) 9 (35) Number of Prior Anti-Cancer Regimens Median 3 Min, Max 1, 7 Prior ASCT, n (%) 13 (50) Pre
Slide 12: Proof of Concept of Tipifarnib in AITL
Proof of Concept of Tipifarnib in AITL Total AITL pts treated 26 Efficacy evaluable 20 Overall Best Response Complete Response (CR) 5 Partial Response (PR) 5 Stable Disease (SD) 3 Progressive Disease (PD) 7 Not efficacy evaluable (NE)/Not yet evaluable 5/1 PPS1 mITT Overall Response Rate (CR + PR) 5
Slide 13: Durable Clinical Responses with Tipifarnib in AITL
Durable Clinical Responses with Tipifarnib in AITL Median Duration of Treatment (DOT) = 3.2 months (95% CI 1.7, 30.6) Median DOT for pts with SD/PR/CR = 7.4 months (95% CI 3.2, 30.6) Time on Treatment (months) Preliminary data as of 11 Nov 2019 CR PR SD PD NE 61st ASH Annual Meeting & Exposition, Ab
Slide 14: Significant Reduction in Tumor Burden with Tipifarnib Treatment
Significant Reduction in Tumor Burden with Tipifarnib Treatment ORR = 50% (PPS), 38 % (mITT) % Maximum Change in SPD Median Duration of Response = 6.6 months (95% CI 0.0, 28.8) Preliminary data as of 11 Nov 2019 Measurement data not available: 1 PD and 6 NE pts 61st ASH Annual Meeting & Exposition,
Slide 15: Using KIRs to Select Responders
Using KIRs to Select Responders 61st ASH Annual Meeting & Exposition, Abstract 468 16
Slide 16: Killer Cell Immunoglobulin-Like Receptor (KIR)
Killer Cell Immunoglobulin - Like Receptor (KIR) 3DS 2DS • KIRs = transmembrane glycoproteins expressed in NK/T cells • Control chemokine/cytokine release and angiogenesis. -P Src • KIR-DS receptors signal intracellularly through ITAM -P ITAM motifs and Src 3DL 2DL • KIR-DL receptors signal through
Slide 17: KIR Variants are associated with Low CXCL5
KIR Variants are associated with Low CXCL5 • Structure and function of KIRs were evaluated in patient tumor samples. • Expression of IL-18 and CXCL5 were significantly lower in AITL tumors carrying KIR3DL2 C336R/Q386E variants. • CXCL5 is potentially a mechanism of resistance to tipifarnib. • No eff
Slide 18: High Activity of Tipifarnib in AITL with KIR3DL2 C336R/Q386E Variants
High Activity of Tipifarnib in AITL with KIR3DL2 C336R/Q386E Variants Ten of 19 DNA sequenced tumors carried C336R/Q386E gene variants of KIR3DL2 and were highly sensitive to tipifarnib. KIR3DL2 C336R variant allele frequency (VAF) correlated with KIR3DL2 KIR3DL2 quality of response. C336R/386E^ Wil
Slide 19: Safety and tolerability of tipifarnib in AITL
Safety and tolerability of tipifarnib in AITL • TEAEs were consistent with the known safety profile of tipifarnib. Most frequently observed TEAEs (all grades, ≥ 10% pts) were hematological-related events (thrombocytopenia, neutropenia, anemia and leukopenia). Grade 3 or Higher Study Drug Related TEA
Slide 20: Conclusions
Conclusions • Tipifarnib is active in AITL pts; ORR = 50% (PPS), 38% (mITT) • Patients with high CXCL12 expression and KIR3DL2 gene variants provide a robust tool for the selection/stratification of AITL patients; ORR = 70% (PPS/mITT). • Side effects are similar to past experience and are primarily
Slide 21: Acknowledgements
Acknowledgements • Patients, their families and caregivers • Study Investigators and their study teams • Kura Oncology 61st ASH Annual Meeting & Exposition, Abstract 468 22
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