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

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FROM CODE TO CURE

www.cgen.com

Q2 2017 Earnings Conference Call

August 2 ,2017

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COM701 Preclinical Data

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• 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

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COM701: LEAD CHECKPOINT INHIBITOR

From computer prediction to functional activity in preclinical models

IND FILING TARGETED FOR Q1 2018

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h Ig G 4 C O M 7 0 1 T IG IT C O M 7 0 1 + T IG IT P D

1 0 0 2 0 0 3 0 0 4 0 0

T c e ll: C M V p p 6 5 s p e c ific C D 8

IFN  (p g /m L )

+ 4 0 % + 9 8 % + 2 4 5 %

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IN VITRO ENHANCEMENT OF T-CELL ACTIVATION BY COM701 MONOTHERAPY AND COMBINATION EFFECTS

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Anti-TIGIT combination Anti-PD1 combination

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• 1

• 1

1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 IFN  (p g /m L ) + 2 4 5 % + 1 0 4 % + 2 1 4 % + 3 3 5 % 

Triple combination

COM701 IN VITRO EFFECTS MATCH PD1 INHIBITOR

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KNOWN INTERACTIONS OF THE PD-1 AND TIGIT/PVRIG PATHWAYS SUPPORT COMBINATION RATIONALE

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Tumor/ APC

• PVRIG

DNAM TIGIT PVRL2 PVR

• PD1

PDL1

Tumor/ APC

T Cell

MULTI-PATHWAY BLOCKADE MAY BE REQUIRED IN CERTAIN PATIENT POPULATIONS

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5

7 1 0 1 3 1 6 2 0 2 3 2 7 1 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 5 0 0 0

W ild -ty p e rIg G 2 b

D a y s p o s t-tu m o r im p la n ta tio n T u m o r v o lu m e (m m 3 )

WT

7 1 0 1 3 1 6 2 0 2 3 2 7 1 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 5 0 0 0

D a y s p o s t-tu m o r im p la n ta tio n T u m o r v o lu m e (m m 3 )

PVRIG-/-

*

5 1 0 1 5 2 0 2 5 3 0 5 0 0 1 0 0 0 1 5 0 0 2 0 0 0 2 5 0 0 3 0 0 0 3 5 0 0 4 0 0 0

D a y s v o lu m e (m m

3)

W ild -ty p e P V R IG

• /-

Ganguly and Pardoll, Johns Hopkins Univ. MC38 model

PVRIG KNOCKOUT REDUCES TUMOR GROWTH AND SUPPORTS MONOTHERAPY APPROACH

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Tumor growth in PVRIG-/- mice

A B

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PVRIG KNOCKOUT AND ANTI-PD-L1 COMBINES IN PRODUCING TUMOR GROWTH REDUCTION

Ganguly and Pardoll, Johns Hopkins Univ. MC38 model

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WT PVRIG KO PVRIG KO + anti-PD-L1 WT + anti-PD-L1

W ild -ty p e a n ti-P D L 1

0 2 9 K O a n ti-P D L 1

7 1 0 1 3 1 6 2 0 2 3 2 7 1 5 0 0 3 0 0 0 4 5 0 0 D a y s p o s t-tu m o r im p la n ta tio n T u m o r v o lu m e (m m

WT = wild type KO = knockout

WT WT + anti-PD-L1 PVRIG KO PVRIG KO + anti-PD-L1

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mIgG1+ rIgG2b αPD-L1+rIgG2b αPD-L1+AB 407

5 1 0 1 5 2 0 2 5 2 5 0 5 0 0 7 5 0 1 0 0 0 1 2 5 0 1 5 0 0 1 7 5 0

D a y s V o lu m e m m

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** *

2 0 4 0 6 0 8 0 1 0 0 5 0 1 0 0

Tim e

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BLOCKING PVRIG IN COMBINATION WITH ANTI-PDL-1 REDUCES TUMOR GROWTH AND INCREASES OF SURVIVAL

Tumor growth Survival

CT26 syngeneic model

*p = 0 .0 4 4 ; T F = 4 /1 0 ***p = 0 .0 0 0 5 ; T G I= 5 6 %

      

    

   



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    m m

     m m



P e rc e n t s u rv iv a l

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    P 

PD-L1+rlgG2b

    P 

PD-L1+Ab 407

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TIGIT KNOCKOUT AND PVRIG BLOCKADE SYNERGIZE IN REDUCING TUMOR GROWTH

Tumor growth; B16 model

B16-Db- gp100 model

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TGI compared to WT + mIgG1 Day 11 Day 14 Day 18 WT+ aPVRIG 17% 13% 8% TIGIT-KO + mIgG1 17% 17% 13% TIGIT-KO + aPVRIG 63% 53% 49% * p < 0.05 ANOVA

5 1 0 1 5 2 0 5 0 0 1 0 0 0 1 5 0 0 2 0 0 0 2 5 0 0

D a y s

V o lu m e (m m

3) W T + a -m P V R IG T IG IT K O + m Ig G 1 T IG IT K O + a -m P V R IG W T + m Ig G 1

*

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W T + m Ig G 1

W T + a P V R IG

T IG IT K O + m Ig G 1

T IG IT K O + a P V R IG

WT + migG1 TIGIT KO + migG1 TIGIT KO + aPVRIG WT + aPVRIG

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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

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