Corvus Pharmaceuticals, Inc. · NASDAQ:CRVS
Corvus Pharmaceuticals — Technical Presentation (2022)
15 slides from Corvus Pharmaceuticals's technical presentation, 2022
Slide 1: ITK Inhibitor Induces Dose-Dependent Th1 Skewing in Normal T Cells and is Active in Refractory T Cell Lymphomas
American Society of Hematology 2022, Poster 3993 ITK Inhibitor Induces Dose-Dependent Th1 Skewing in Normal T Cells and is Active in Refractory T Cell Lymphomas Ryan Wilcox, MD, PhD Section Head, Lymphoma & Myeloma Associate Professor, Department of Internal Medicine, Division of Hematology/Oncology
Slide 2: Introduction
Introduction • ITK (IL-2 inducible T cell kinase) is expressed in T cells with an important role in T cell receptor signaling and T helper cell differentiation. • Resting lymphocyte kinase (RLK) is a closely related kinase involved in the differentiation of naïve T cells into Th1 T cells • ITK-/- mi
Slide 3: ITK Plays Critical Roles in T Helper Cell Differentiation
ITK Plays Critical Roles in T Helper Cell Differentiation ITK involved in many diseases ITK blockade leads to increase in Th1 and CPI-818 is selective for ITK reduction in Th2, Th17 Closely related Tec Kinases CPI-818 K D* (nM) Th1 cells play a role in cancer cell and viral elimination ITK 2.5 BLK 4
Slide 4: Methods and Trial Design
Methods and Trial Design PHASE 1 CLINICAL TRIAL IN REFRACTORY IN VITRO AND PRECLINICAL STUDIES PERIPHERAL T CELL LYMPHOMAS • Serum cytokines measured using MSD • Eligibility: failed all standard prior therapies immunoassay format • Histologies: cutaneous T-cell lymphoma • Lymphocyte subsets enumerat
Slide 5: Treatment of Murine EL4 T Cell Lymphoma with CPI-818
Treatment of Murine EL4 T Cell Lymphoma with CPI-818 Tumor growth inhibition and increases in CD8+ T cell infiltration Mice with established EL4 tumors (CD4+) were treated with CPI-818 10, 30 mg/kg or vehicle daily for 7 days and tumor measurements/excision were made at Day 22 (3 days after dosing).
Slide 6: CPI-818 induces Th1 skewing in vitro in Normal PBMC
CPI-818 induces Th1 skewing in vitro in Normal PBMC Concentration dependent effects Th1 cells (ratio IFNg:IL-4) dose High concentrations block T cell response effect in vitro proliferation in vitro 15 100 3 Viability (cells/ml x 106) 90 Viability (%) 10 2 80 Th1 Cells 70 5 1 60 0 50 0 0.001 0.01 0.1
Slide 7: Phase I Trial Pharmacokinetic Analysis
Phase I Trial Pharmacokinetic Analysis Dose of 200mg achieves levels needed for Th1 skewing In vivo CPI-818 Plasma Concentration mM* Dose (mg) Cmax (Std Dev) Cmin (Std Dev) • PK studies indicate 200 mg dose provides optimum plasma 100 (N=4) 1.3 (1.0) 0.04 (0.1) concentration for Th1 skewing. 200 (N=
Slide 8: Effects of CPI-818 on In Vitro T Cell Cytokine Production
Effects of CPI-818 on In Vitro T Cell Cytokine Production CPI-818 inhibits Th2 cytokine production from normal CD4+ and Sezary cells 150 IL-4 IL-5 IL-13 IFNg % untreated control 100 FACS-sorted CD4+ T cells from healthy controls (n=3; top panel) 50 or from Sezary patients (n=2; bottom panel) were ac
Slide 9: Interim Phase 1 Trial Results
Interim Phase 1 Trial Results Patient characteristics and adverse event summary 100mg 200mg 400mg 600mg (N=4) (N=13) (N=10) (N=16) Age (yrs), median (range) 51 (29, 75) 59 (29, 81) 66.5 (36, 80) 63.5 (34, 84) Gender, male N (%) 3 (75) 4 (31) 6 (60) 8 (50) No. of prior therapies, median (range) 3.5 (
Slide 10: Anti-tumor Activity in Various Dosing Cohorts
Anti-tumor Activity in Various Dosing Cohorts 200 mg BID identified as optimal dose with ORR of 4/11 evaluable Data cut-off: September 2022 10
Slide 11: Anti-tumor Activity in Refractory Disease
Anti-tumor Activity in Refractory Disease Regression of large tumor masses observed • PTCL-NOS patient failed CHOEP, GDP, HDACi, and anti-PD1. • Large subcutaneous mass on abdomen. • Has PR 8+ months duration in all sites of disease (bone marrow, skin, lymph node, and spleen) on CPI-818. Screening D
Slide 12: Immunologic Effects in Treated Patient
Immunologic Effects in Treated Patient Optimum dose induces Th1 skewing and Th2 blockade Frequency of Th1 & Th17 CD4 cells in Blood Effects on Eosinophils and Serum IL-5 50 CXCR3+(CD183+)Th1 cells 20 100 % CD4+ T Cell in blood Absolute Count (x10^9/L) 40 CCR6+(CD196+)Th17 cells 17.18 IL-5 Conc (pg/m
Slide 13: Effects of CPI-818 on Differentiation of Th1 and CD8+ TEMRA Cells
Effects of CPI-818 on Differentiation of Th1 and CD8+ TEMRA Cells Percent Change in Th1 and CD8+ TEMRA Cells from Baseline Peripheral blood from four patients were collected at various timepoints and T cell subsets evaluated by flow cytometry. Plots show percent change from baseline for Th1 (CD3+/CD
Slide 14: Conclusions
Conclusions • CPI-818 is a selective ITK inhibitor that at optimal concentrations induces Th1 skewing and blockade of Th2 function and related cytokine production (e.g., IL-4, IL-5, IL-13, TARC). • In an ongoing international Phase 1 trial: – Durable objective responses seen (1 CR, 25 mo; 1 nodal CR
Slide 15: Acknowledgements
Acknowledgements • Participating Centers and Investigators: Seoul National University Hospital Hackensack University Asan Medical Center Medical Center United States University of Michigan Samsung Medical Ohio State University Pusan National Peking University South Korea Beijing Cancer Hospital Univ
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