Corvus Pharmaceuticals, Inc. · NASDAQ:CRVS
Corvus Pharmaceuticals — Technical Presentation (June 2019)
17 slides from Corvus Pharmaceuticals's technical presentation, Jun 3, 2019
Slide 1: Immunobiology, Preliminary Safety and Efficacy of CPI-006 in a Phase 1 Trial in Advanced Cancers
Immunobiology, Preliminary Safety and Efficacy of CPI - 006, an Anti - CD73 Antibody with Immune Modulating Activity, in a Phase 1 Trial in Advanced Cancers 1 Jason J. Luke*, John D. Powderly II, Jaime R. Merchan , Minal A. Barve , Andrew N. Hotson, Mehrdad Mobasher, Long Kwei, Gabriel Luciano, Jose
Slide 2: Background
Background Jason J. Luke, MD 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 • Adenosine in the tumor microenvironment is immunosuppressive • CD73 is an ectoenzyme present on many tissu
Slide 3: CPI-006 Blocks CD73 Enzymatic Activity
0 5 10 15 20 0 200 400 600 Day of Treatment T u m o r V o l u m e ( m m 3 ) PBS isotype CPI-006 p < 0.0001 0.1 1 10 100 1000 10000 0.0 0.2 0.4 0.6 0.8 1.0 mAb [nM] p h o s p h a t e ( a b s o r b a n c e 6 6 0 n m ) CPI-006 isotype 1mM APCP CPI - 006 Blocks CD73 Enzymatic Activity 3 Jason J. Luke, M
Slide 4: Immunomodulatory Activities of CPI-006 are Adenosine Independent
Immunomodulatory Activities of CPI - 006 are Adenosine Independent 4 • Healthy donor PBMC treated overnight • Flow cytometry analysis of surface markers on B cells (CD19 POS CD3 NEG ) Jason J. Luke, MD Activation Markers Antigen Presentation • Lymphocyte markers are consistent with activation of B c
Slide 5: Clinical Trial Design
Clinical Trial Design Design • Phase 1/1b open label, 3 + 3 dose escalation/dose expansion • CPI - 006 given as 1 hour IV infusion every 3 weeks; fixed dose of ciforadenant (100 mg po BID) for combo Eligibility • Advanced cancers progressed on 1 - 5 prior therapies • ECOG status 0 or 1 • CD73 expres
Slide 6: Patient Characteristics
Patient Characteristics 6 Jason J. Luke, MD Baseline Demographics Description CPI - 006 (N=12) CPI - 006 + ciforadenant (N=8) Age ( yrs ), median (range) 62 (46, 78) 64 (36, 86) Gender, male n (%) 10 (83) 8 (100) No. of prior therapies, median (range) 4 (1, 5) 4 (3, 7) Histologies N N Bladder Cancer
Slide 7: Adverse Events
Adverse Events 7 Jason J. Luke, MD Adverse Events N(%) CPI - 006 Monotherapy (N=12) CPI - 006 + Ciforadenant (N=8) All Grades Grade 3 or 4 All Grades Grade 3 or 4 Subjects with any TEAE 8 ( 66.7) 1 ( 8.3) 5 ( 62.5) 0 ( 0.0) Anemia 1 ( 8.3) 1 ( 8.3) 1 ( 12.5) 0 ( 0.0) Diarrhea 1 ( 8.3) 0 ( 0.0) 1 ( 1
Slide 8: Pharmacokinetics and Receptor Occupancy
Pharmacokinetics and Receptor Occupancy 8 Jason J. Luke, MD Serum Pharmacokinetics Peripheral CD8 Receptor Occupancy • Exposure increases and clearance decreases with increasing dose • CPI - 006 detectable for 21 days after a single dose of 6 mg/kg or higher • Total cell surface CD73 unchanged; CPI
Slide 9: Occupancy and Inhibition of CD73 in the Tumor
Occupancy and Inhibition of CD73 in the Tumor 9 Jason J. Luke, MD • Colorectal patient treated with 12 mg/kg CPI - 006 • Tumor biopsy of retroperitoneal lesion obtained at trough pre - dose 3 On - Treatment Bx Non - Competitive Anti - CD73 Competitive Anti - CD73 CD73 Enzyme Activity Positive Contro
Slide 10: Disease Control with Monotherapy and Combination
10 Jason J. Luke, MD • Higher doses appear to be providing longer term disease control with monotherapy • Combination appears to improve disease control Disease Assessment Cycle = 21 days Disease assessment every 3 - 4 cycles
Slide 11: Treatment Induces Rapid Changes in PBMCs
C D 4 C D 7 3 + C D 4 C D 7 3 - C D 8 C D 7 3 + C D 8 C D 7 3 - M o n o c y t e s 0.0 0.5 1.0 1.5 2.0 2.5 Cell Type F o l d C h a n g e i n C e l l F r e q u e n c y 20190509 SA combo dots T cells monos Treatment Induces Rapid Changes in PBMCs 11 Jason J. Luke, MD Changes in PBMCs at 0.5 Hour CD73 P
Slide 12: Changes in Blood B Cells Over Time
Changes in Blood B Cells Over Time 12 Jason J. Luke, MD Changes in CD73 POS B cells • CD73 POS B cells drop with each infusion and partially return reaching new steady state • Consistent with redistribution of B cells to lymphoid tissue • Increased expression of HLA - DR Changes in HLA - DR Expressi
Slide 13: Changes in CD73 POS B Cells & Tumor Reduction in a Prostate Cancer Patient
Changes in CD73 POS B Cells & Tumor Reduction in a Prostate Cancer Patient 13 • Decrease in target lesion in patient receiving 6 mg/kg monotherapy, treatment ongoing through 11 cycles Jason J. Luke, MD Changes in Circulating B Cells Pre - treatment Post cycle 2 • 72 year old man with widely metastat
Slide 14: Treatment Induces Cytokines Consistent with Immune Activation
Treatment Induces Cytokines Consistent with Immune Activation 14 Jason J. Luke, MD • Rapid induction of inflammatory cytokines • Subsequent induction of C - reactive protein and serum amyloid A • These findings are consistent with early inflammatory response Fold change in Serum Analytes N=3, 6mg/kg
Slide 15: Proposed Model for Immunomodulatory Activity
Proposed Model for CPI - 006 Immunomodulatory Activity 15 Jason J. Luke, MD AMP Adenosine CD73 B cell Activation Lymphoid tissue • Migration to and retention in lymph nodes. • Increased antigen presentation. CPI - 006 CD69 S1P1 BTK ERK B cell
Slide 16: Conclusions
Conclusions • CPI - 006 has novel immunomodulatory activity with dual mechanisms of action: – Affects B cell trafficking and increases expression of CD69 and other markers consistent with increased antigen presentation by APCs – Complete inhibition of CD73 enzyme activity without internalization • C
Slide 17: Acknowledgements
Acknowledgements • The patients and their families • Participating Centers : Carolina BioOncology Institute, University of Chicago, Medical College of Wisconsin, Roswell Park Cancer Institute, Yale University, Mount Sinai, Icahn School of Medicine, Dana Farber Cancer Institute, Mary Crowley Cancer C
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