Compugen Ltd. · NASDAQ:CGEN
Compugen — SITC Targets for Cancer Immunotherapy: A Deep Dive Seminar Series (June 2021)
19 slides from Compugen's conference presentation, Jun 29, 2021
Slide 1: The TIGIT Pathway: PVRIG, a Novel Pathway Member
THE TIGIT PATHWAY PVRI G, a Nove l Pat hway M e mber Ta r g e t s f o r C a n c e r I m m u n o t h e r a p y : A D e e p D i v e E r a n O p h i r, V P R e s e a r c h & D r u g D i s c o ve r y June 2021
Slide 2: The DNAM-1 Axis
The DNAM-1 Axis • DNAM-1 axis plays an essential role in tumor immunology • PVRIG binds PVRL2 as a functional ligand (TIGIT has a low affinity for PVRL2) • DNAM-1 axis – two parallel dominant complementary inhibitory pathways (PVRIG & TIGIT/CD96?) • TIGIT and PVRIG deliver direct inhibitory signal i
Slide 3: DNAM-1 Intersects with the PD-1 Pathway and is Required for In-vivo Response to PD-1 Blockade
DNAM-1 Intersects with the PD -1 Pathway and is Required for In-vivo Response to PD -1 Blockade PD-1 inhibition blocks DNAM-1 DNAM-1 KO or inhibition reverses a-PD-1 tumor (CD226) dephosphorylation and growth inhibition inactivation Wang et al., Science Immunology, 2018 Weulersee et al. immunity 201
Slide 4: PVRIG, TIGIT and PD-1 as Players in the DNAM-1 Axis
P V R I G , T I G I T a n d P D - 1 a s P l aye rs i n t h e D N A M - 1 A x i s Alteber et al. Cancer Discov. 2021 4
Slide 5: Potential Intersection Between PVRIG/TIGIT and PD-1 Pathways Support Combination Approach
Potential Intersection Between PVRIG/TIGIT and PD -1 Pathways Support Combination Approach to Overcome Immunotherapy Resistance Alteber et al. Cancer Discov. 2021 Different tumor types may respond to different combinations depending on dominance of the pathways 5
Slide 6: Synergistic T Cell Activation With PVRIG, PD-1 and TIGIT Blockade
Synergistic T Cell Activation With PVRIG, PD-1 and TIGIT Blockade COM701 +/- anti-TIGIT COM701 +/- anti-PD-1 Triple combination Whelan, et al., Cancer Immunol Res. 2019 COM701 –PVRIG blocking antibody 6
Slide 7: Growing Evidence of T Stem-like Cells Importance in IO
G r o w i n g E v i d e n c e o f T s t e m - l i ke C e l l s I m p o r t a n c e i n I O Fraction of TCF7+ cells is a • Anti-PD-L1 expands a predictive of PD-1 response key population of PD-1- in melanoma positive Tscm which also express TIGIT • TIGIT and PD-1 co- blockade might enable optimal Tsc
Slide 8: PVRIG is Expressed by T Stem-like Cells
P V R I G i s E x p re s s e d b y T S te m - l i ke C e l l s NSCLC CD8+ Tscm cells CD8+ Tex cells PVRIG Expression (Log 2 FOI) PVRIG Expression (Log2 FOI) 32 32 PVRIG TIGIT PD1 16 16 RNA Expression 8 8 4 4 2 2 1 1 0.5 0.5 0.25 0.25 TSCM Exhausted TSCM Exhausted TSCM Exhausted l do ng l l do ng l n
Slide 9: PVRIG Uniquely Clusters with Early Memory Differentiation/Stem-like Genes
PVRIG Uniquely Clusters with Early Memory Differentiation/ S t e m - l i ke G e n e s PCA Analysis of CD8+ T cell genes, NSCLC Unsupervised correlation analysis of scRNA, CRC Cytotoxic Naïve TRM Exhausted Early Memory GSE99254_NSCLC Dataset internally analyzed GSE108989_CRC Dataset internally analyz
Slide 10: PVR and PVRL2 are Expressed in Inflamed and Non-Inflamed Tumors
P V R a n d P V R L 2 a r e E x p r e s s e d i n I n f l a m e d a n d N o n - I n f l a m e d Tu m o r s PVR/PVRL2 on tumor cells induced by: PVR/PVRL2 on Tumor 1. Genotoxic stress (DNA damage, oxidative stress) Cells are not 2. Tumorigenesis (loss of contact inhibition/increased invasiveness) Mod
Slide 11: PVRL2 Has A Dominant Expression on Dendritic Cells
PVRL2 Has A Dominant Expression on Dendritic Cells DC Population in SCC/BCC GSE123814 Dataset internally analyzed PVRIG blockade may enhance interaction and activation of Tscm by DCs in PD-L1low non-inflamed indications 11
Slide 12: PVRL2 and PVRIG Expression in Tertiary Lymphoid Structures
P V R L 2 a n d P V R I G E x p r e s s i o n i n Te r t i a r y Ly m p h o i d S t r u c t u r e s PVRL2 PVRL2 PVRIG PVRIG Tertiary lymphoid structures are Lymphoid Structures in the tumor bed in which local T cell activation occur • Predictive of PD1 response TNBC Sample, Internal Data Helmink et
Slide 13: COM701 Clinical Program
COM701 Clinical Program Phase 1 Arm A - Monotherapy Phase 1 Arm B – Dual Combination Dual Combination: Escalating doses of Monotherapy Monotherapy Cohort Expansion Dual combination Cohort Expansion COM701 with fixed dose of Opdivo® (Up to Dose Escalation (20 patients; progressed on SOC) (progressed
Slide 14: COM701 Monotherapy and Nivolumab Combination Therapy: Swimmer Plot
COM701 Monotherapy and Nivolumab Combination Therapy: SWIMMER PLOT ASCO, June 2021, Vaena et al., Oral presentation 14 Preliminary anti-tumor activity also in patients with PVRL2+PDL1low tumors
Slide 15: Confirmed Partial Response in Patient with Primary Peritoneal PD-L1 Negative Cancer
Confirmed Partial Response in Patient with Primary Peritoneal P D - L 1 N e g a t i v e C a n c e r Tr e a t e d w i t h C O M 7 0 1 M o n o t h e r a p y PVRL2 PDL1 ASCO, June 2021, Vaena et al., Oral presentation PR in patient with non-inflamed TME demonstrating immune activation in peripheral blo
Slide 16: Summary
Summary • PVRIG is a novel checkpoint in the DNAM-1 axis, co-expressed with PD-1 and TIGIT in Tscm and exhausted T cells but uniquely clusters with early memory differentiation/ stem-like genes • PVRIG blockade show synergistic activity with TIGIT and PD-1 blockade in pre-clinical studies • PVRL2 an
Slide 17: Safe Harbor Statement
S a fe H a r b o r S tate m e nt This presentation contains “forward-looking statements” within the meaning of the the Securities Act of 1933 and the Securities Exchange Act of 1934, as amended, and the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking s
Slide 18: Our Vision
Our Vision Transforming patient lives by developing first- in-class therapeutics based on Compugen’s computational target discovery platform From Code to Cure® 18
Slide 19: Thank you.
Thank you.
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