Corvus Pharmaceuticals, Inc. · NASDAQ:CRVS
Corvus Pharmaceuticals — SITC 2019
18 slides from Corvus Pharmaceuticals's conference presentation, Nov 8, 2019
Slide 1: SITC 2019
SITC 2019 . Nov. 6-10 NATIONAL HARBOR, MARYLAND © SIC D soxiety for immunotherapy of Cancer
Slide 2: Immunobiology and Clinical Activity of CPI-006, an Anti-CD73 Antibody in a Phase 1/1b Trial
Immunobiology and Clinical Activity of CPI - 006, an Anti - CD73 Antibody with Immunomodulating Properties in a Phase 1/1b Trial in Advanced Cancers Luke JJ, Merchan J, Harshman LC, Marron T, Powderly J, Barve M, LoRusso P, Johnson M, Hotson A, Gittelman R, Munneke B, Buggy J, Willingham S, Piccione
Slide 3: Disclosures
Disclosures Jason J. Luke : University of Pittsburgh Medical Center, Pittsburgh The following relationships exist related to this presentation: • Data and Safety Monitoring Board: TTC Oncology • Scientific Advisory Board: 7 Hills, Actym , Alphamab Oncology, Mavu , Pyxis, Springbank , Tempest • Consu
Slide 4: CD73 pathway and CPI-006 mechanism
AMP Adenosine CD73 CD73 CD73 CD73 Activation Dendritic Macrophage B Cell MHC TCR Ligand? CPI - 006 mimics ligand (agonist) APCs A2AR CPI - 006 Ciforadenant T cell • CD73 is an ectoenzyme present on many tissues including subsets of T and B cells – Converts AMP to adenosine – Functions in lymphocyte
Slide 5: CPI-006 is an Anti-CD73 with Unique Properties
CPI - 006 is an Anti - CD73 with Unique Properties CPI - 006 induces B cell differentiation: isotype switching and immunoglobulin secretion in vitro • CPI - 006 activates B cells, resulting in morphological and surface marker changes consistent with B cell differentiation and isotype class switching
Slide 6: CPI-006 Clinical Trial Design
CPI - 006 - 001 Clinical Trial Design Design • Phase 1/1b dose escalation/dose expansion in disease specific cohorts • CPI - 006 every 3 weeks; fixed dose of ciforadenant Eligibility • Cancers progressed on 1 - 5 prior therapies • CD73 expression: required in expansion, not in dose escalation • Aden
Slide 7: Patient Characteristics
Patient Characteristics Total Patients N=40 CPI - 006 (N = 24) CPI - 006 + Ciforadenant (N=16) Age ( yrs ), median (range) 62 (46, 78) 67 (36, 86) Gender, male N (%) 18 (75) 12 (75) No. of prior therapies, median (range) 4 (1, 6) 4 (2, 7) Histologies N N Renal Cell Cancer 2 4 Non - small cell lung c
Slide 8: Adverse Events
Adverse Events Adverse Events N (%) CPI - 006 Monotherapy (N=24) CPI - 006 + Ciforadenant (N= 16) All Grades Grade 3 or 4 All Grades Grade 3 or 4 Patients with any TEAE 18 ( 75.0) 4 ( 16.7) 12 ( 75.0) 2 ( 12.5) Anemia 1 ( 4.2) 1 ( 4.2) 2 ( 12.5) 1 ( 6.3) Lymphopenia 2 ( 8.3) 1 ( 4.2) 0 ( 0.0) 0 ( 0.
Slide 9: Pharmacokinetics and Receptor Occupancy
Pharmacokinetics and Receptor Occupancy 1 m g / k g 3 m g / k g 6 m g / k g 1 2 m g / k g 1 8 m g / k g 2 4 m g / k g 0 50 100 150 Dose (mg/kg) B c e l l o c c u p a n c y a t e n d o f c y c l e B cell trough 2b • Sustained CD73 occupancy of peripheral blood at ≥ 6 mg/kg • Full tumor occupancy obse
Slide 10: Treatment Induces Rapid Changes in Blood B and T Cells
Treatment Induces Rapid Changes in Blood B and T Cells 10 • Changes in B cells (but not T cells) appear to be CD73 expression dependent • B cell numbers partially return by 21 days; T cells fully return p < 0.0001
Slide 11: Increase in Memory B Cells in Returning Lymphocytes
Increase in Memory B Cells in Returning Lymphocytes Pre - treatment 30 min (Reduced B cells) Day 21 (Returning B cells: Memory Phenotype) Increased % class - switch memory cells No change in % class - switch memory cells CD27 IgD • At 0.5 hours no change in proportion of naïve and memory B cells; re
Slide 12: Significant Expansion of New B and T cell Clones
Significant Expansion of New B and T cell Clones Differential Abundance Plots of B cell Clonal Expansion Cohort Number of Patients with B Cell Expansion Number of Patients with T Cell Expansion CPI - 006 monotherapy 5 of 7 2 of 4 CPI - 006 + ciforadenant 2 of 4 1 of 4 Total 7 of 11 3 of 8 10 -5 10 -
Slide 13: Response Assessments
Response Assessments • Response assessments in patients receiving ≥ 6 mg/kg dose
Slide 14: Tumor Reduction in a Prostate Cancer Patient
Tumor Reduction in a Prostate Cancer Patient CPI - 006 monotherapy 14 • Decrease in target lesion in patient receiving 6 mg/kg monotherapy, treatment ongoing through 19 cycles Pre - treatment Post cycle 2 • 72 year old man with widely metastatic prostate cancer; previous therapies include leuprolide
Slide 15: Responding Pulmonary Metastases in RCC Patient
Responding Pulmonary Metastases in RCC Patient CPI - 006 6 mg/kg plus ciforadenant combination • 36 year old male presented in 2015 with renal mass and bone metastases • Failed TKI, nivo and nivo / ipi with increase pulmonary mets • Regression of multiple biopsy proven pulmonary metastases on CPI -
Slide 16: Model for CPI-006 Effects on B Cells
Model for CPI - 006 Effects on Cells CPI - 006 Memory B cell Naïve B cell Activated B cell Plasmablast Lymph node Blood IgD + CD19+ CD20+ CD27 - CD73+ IgD - CD19+ CD20+ CD27+ CD73+ CD19+ CD20+ CD25+ CD69+ CD83+ HLA - DR↑ CD73+ IgM,G secreted IgD - CD19+ CD20 - CD27+ CD38+ HLA - DR - CD73 -
Slide 17: Conclusions
Conclusions • CPI - 006 has novel immunomodulatory activities: • Induces differentiation of B cells, class switching, secretion of immunoglobulin (in vitro), and generation of memory B cells • Increases expression of CD69 and other markers consistent with increased antigen presentation by APCs • The
Slide 18: Acknowledgements
Acknowledgements • The patients and their families • Participating Centers and Investigators : Dana Farber Cancer Institute, Medical College of Wisconsin, Monash Health, Mount Sinai Icahn School of Medicine, University of California San Francisco Medical Center, University of Chicago, University of