Q2 2017 Earnings Conference Call COM701 Preclinical Data August 2 - PowerPoint PPT Presentation

TM FROM CODE TO CURE Q2 2017 Earnings Conference Call COM701 Preclinical Data August 2 ,2017 www.cgen.com 1

COM701: LEAD CHECKPOINT INHIBITOR From computer prediction to functional activity in preclinical models • COM701 is a high affinity monoclonal antibody targeting PVRIG • PVRIG (CGEN-15029) identified as novel immune checkpoint by Compugen and plays a unique role in the validated TIGIT axis • COM701 is synergistic with anti-TIGIT and anti-PD-1/L1 as a potential cancer immunotherapy treatment • First-in-class opportunities as mono- and combination therapies IND FILING TARGETED FOR Q1 2018 2 1

IN VITRO ENHANCEMENT OF T-CELL ACTIVATION BY COM701 MONOTHERAPY AND COMBINATION EFFECTS Anti-TIGIT combination Anti-PD1 combination Triple combination T c e ll: C M V p p 6 5 s p e c ific C D 8 4 0 0 + 2 4 5 % 5 0 0 + 3 3 5 % 3 0 0 4 0 0 IFN  (p g /m L ) + 2 4 5 % IFN  (p g /m L ) + 9 8 % + 2 1 4 % 3 0 0 2 0 0 + 1 0 4 %   2 0 0 + 4 0 % 1 0 0 1 0 0 0 4 1 1 1 T - - - G 0 I D D D G g P P P I I h T + C O M 7 0 1 + T IG IT + + h Ig G 4 C O M 7 0 1 T IG IT + 1 T T 0 P D 1 I I 7 G G 0 M I I 7 T T M O + O C 1 C 0 7 M O C COM701 IN VITRO EFFECTS MATCH PD1 INHIBITOR 3 2

KNOWN INTERACTIONS OF THE PD-1 AND TIGIT/PVRIG PATHWAYS SUPPORT COMBINATION RATIONALE PVRIG PVRL2 T Cell - PDL1 PD1 Tumor/ - Tumor/ + DNAM APC APC - PVR TIGIT MULTI-PATHWAY BLOCKADE MAY BE REQUIRED IN CERTAIN PATIENT POPULATIONS 4 3

PVRIG KNOCKOUT REDUCES TUMOR GROWTH AND SUPPORTS MONOTHERAPY APPROACH Tumor growth in PVRIG-/- mice A B W ild -ty p e rIg G 2 b 4 0 0 0 5 0 0 0 5 0 0 0 PVRIG -/- W ild -ty p e WT T u m o r v o lu m e (m m 3 ) T u m o r v o lu m e (m m 3 ) 3 5 0 0 4 0 0 0 4 0 0 0 -/- 3 0 0 0 P V R IG 3 ) v o lu m e (m m 3 0 0 0 3 0 0 0 D e a d 2 5 0 0 2 0 0 0 2 0 0 0 2 0 0 0 * D e a d 1 5 0 0 D e a d 1 0 0 0 1 0 0 0 1 0 0 0 0 0 7 1 0 1 3 1 6 2 0 2 3 2 7 7 1 0 1 3 1 6 2 0 2 3 2 7 5 0 0 D a y s p o s t-tu m o r im p la n ta tio n D a y s p o s t-tu m o r im p la n ta tio n 0 0 5 1 0 1 5 2 0 2 5 3 0 D a y s Ganguly and Pardoll, Johns Hopkins Univ. MC38 model 5 4

PVRIG KNOCKOUT AND ANTI-PD-L1 COMBINES IN PRODUCING TUMOR GROWTH REDUCTION WT = wild type WT PVRIG KO KO = knockout 5 0 0 0 5 0 0 0 3 ) 3 ) T u m o r v o lu m e (m m T u m o r v o lu m e (m m 4 0 0 0 4 0 0 0 W ild -ty p e rIg G 2 b 4 5 0 0 0 2 9 K O rIg G 2 b 3 0 0 0 D e a d 3 0 0 0 W ild -ty p e a n ti-P D L 1 2 0 0 0 2 0 0 0 D e a d 0 2 9 K O a n ti-P D L 1 3 ) 1 0 0 0 T u m o r v o lu m e (m m D e a d 1 0 0 0 WT 0 0 3 0 0 0 7 1 0 1 3 1 6 2 0 2 3 2 7 7 1 0 1 3 1 6 2 0 2 3 2 7 D a y s p o s t-tu m o r im p la n ta tio n D a y s p o s t-tu m o r im p la n ta tio n WT + anti-PD-L1 WT + anti-PD-L1 PVRIG KO + anti-PD-L1 PVRIG KO W ild -ty p e a n ti-P D L 1 0 2 9 K O a n ti-P D L 1 1 5 0 0 5 0 0 0 5 0 0 0 3 ) PVRIG KO 3 ) T u m o r v o lu m e (m m T u m o r v o lu m e (m m 4 0 0 0 + anti-PD-L1 4 0 0 0 3 0 0 0 3 0 0 0 2 0 0 0 2 0 0 0 0 7 1 0 1 3 1 6 2 0 2 3 2 7 1 0 0 0 1 0 0 0 D e a d D a y s p o s t-tu m o r im p la n ta tio n 0 0 7 1 0 1 3 1 6 2 0 2 3 2 7 7 1 0 1 3 1 6 2 0 2 3 2 7 D a y s p o s t-tu m o r im p la n ta tio n D a y s p o s t-tu m o r im p la n ta tio n Ganguly and Pardoll, Johns Hopkins Univ. MC38 model 6 5

BLOCKING PVRIG IN COMBINATION WITH ANTI-PDL-1 REDUCES TUMOR GROWTH AND INCREASES OF SURVIVAL Tumor growth          Survival ***p = 0 .0 0 0 5 ; T G I= 5 6 %    *p = 0 .0 4 4 ; T F = 4 /1 0 CT26       P e rc e n t s u rv iv a l 1 0 0       syngeneic model 1 7 5 0 5 0 * 1 5 0 0 3 1 2 5 0 V o lu m e m m mIgG1+ rIgG2b 1 0 0 0 0 α PD-L1+rIgG2b 0 2 0 4 0 6 0 8 0 1 0 0 α PD-L1+AB 407 7 5 0 Tim e         5 0 0      P   P PD-L1+rlgG2b PD-L1+Ab 407  ** * 2 2 5 0 2 2 5 0 2 5 0 2 0 0 0 2 0 0 0 1 7 5 0 1 7 5 0 1 5 0 0 1 5 0 0 0 3 3 m m m m 1 2 5 0 1 2 5 0 0 5 1 0 1 5 2 0 2 5 1 0 0 0 1 0 0 0 7 5 0 7 5 0 5 0 0 5 0 0 D a y s 2 5 0 2 5 0 0 0 0 5 1 0 1 5 2 0 2 5 D a y s D a y s 0 1 0 2 0 7 7 6

TIGIT KNOCKOUT AND PVRIG BLOCKADE SYNERGIZE IN REDUCING TUMOR GROWTH WT + migG1 WT + aPVRIG Tumor growth; B16 model W T + m Ig G 1 W T + a P V R IG 3 0 0 0 3 0 0 0 3 ) 3 ) V olu m e (m m 2 0 0 0 V olu m e (m m 2 0 0 0 2 5 0 0 1 0 0 0 1 0 0 0 B16-Db- 3 ) 2 0 0 0 0 0 V o lu m e (m m gp100 0 3 6 9 1 2 1 5 1 8 0 3 6 9 1 2 1 5 1 8 D a y s D a y s 1 5 0 0 TIGIT KO + migG1 TIGIT KO + aPVRIG model T IG IT K O + m Ig G 1 T IG IT K O + a P V R IG 3 0 0 0 3 0 0 0 1 0 0 0 * 3 ) 3 ) 2 0 0 0 V olu m e (m m V olu m e (m m 2 0 0 0 5 0 0 1 0 0 0 1 0 0 0 0 0 5 1 0 1 5 2 0 0 0 0 3 6 9 1 2 1 5 1 8 0 3 6 9 1 2 1 5 1 8 D a y s D a y s D a y s W T + m Ig G 1 W T + a -m P V R IG TGI compared to WT + mIgG1 Day 11 Day 14 Day 18 T IG IT K O + m Ig G 1 T IG IT K O + a -m P V R IG WT+ aPVRIG 17% 13% 8% TIGIT-KO + mIgG1 17% 17% 13% * p < 0.05 ANOVA TIGIT-KO + aPVRIG 8 63% 53% 49% 8 7

COM701 CLINICAL DEVELOPMENT: PHASE 1 STUDY • Dose escalation in multiple tumor types to establish safety and look for signs of monotherapy efficacy • If positive, cohort expansion in target cancer indication(s) • Rapid progression to combination trials with PD1 inhibitors to assess efficacy; Rationale based on: • Pathway interactions • Preclinical in vitro and in vivo synergistic effects 9 8