Slide 1: DNAM-1 Axis Virtual Investor Event with Drew Pardoll
D NAM - 1 Axis Virtual Investor Event with D rew Pardoll 23 May 2023
Slide 2: 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 conduct of its clinical trials as well as significant increased expenditures; Compugen’s Securities Act of 1933 and the Securities Exchange Act of 1934, as amended, and the business mod
Slide 3: From Code to Cure: Compugen advances next generation cancer immunotherapies targeting the DNAM-1 axis
From Code to Cure : Compuge n advanc es the next generation of canc er immunotherapies targeting the D NAM - 1 ax is E r a n O p h i r, P h . D . , S V P R e s e a r c h a n d Drug Discovery
Slide 4: Focus on three novel antibody therapeutics
Fo c u s o n t h re e n ove l a nt i b o d y t h e ra p e u t i c s D i s c o v e r e d b y C o m p u g e n ’s p i o n e e r i n g c o m p u t a t i o n a l d i s c o v e r y e n g i n e COM701 COM902 COM503 Potential 1st in-class Potential best-in-class Novel antibody approach to anti-PVRIG antibod
Slide 5: DNAM-1 axis potential game changer in fight against cancer
D N A M - 1 ax i s p o te nt i a l ga m e c h a n ge r i n f i g ht a ga i n st c a n c e r Blocking PVRIG may be the missing piece when checkpoint inhibitors fail • PVRIG and TIGIT discovered by Compugen’s discovery platform • DNAM axis – two parallel and complementary inhibitory Anti- PD-1 pathway
Slide 6: PVRIG and TIGIT – complementary but distinct pathways
P V R I G a n d T I G I T – c o m p l e m e nta r y b u t d i st i n c t p at hway s PVRIG preferentially binds PVRL2 TIGIT preferentially binds PVR Differentially expressed in Differentially expressed on Differentially expressed in the tumor types immune cell types tumor microenvironment PVRL2 expr
Slide 7: Strong biological rationale for targeting PVRIG in cold tumors
S t ro n g b i o l o g i c a l rat i o n a l e fo r ta rget i n g P V R I G i n c o l d t u m o rs P V R I G + Ts c m i n t e r a c t i o n w i t h P V R L 2 + D e n d r i t i c C e l l s h y p o t h e s i s COM701 may sensitize cold tumors to PD-1 and TIGIT 7 Tscm: Early differentiated stem like me
Slide 8: COM701 mediated clinical benefit in relapsed or refractory patients not responding to immunotherapy
CO M 7 0 1 m e d i ate d c l i n i ca l b e n ef i t i n re l a ps e d o r ref ra c to r y p at i e nt s t y p i c a l l y n o t re s p o n d i n g to i m m u n o t h e ra p y • Monotherapy and in combination with anti -PD-1 ± anti-TIGIT • ICI refractory/experienced • Less inflamed tumors PATIENTS T
Slide 9: PROC patients treated with COM701 + nivolumab ± BMS-986207 – swimmer plots
P RO C p at i e nt s t re ate d w i t h CO M 7 0 1 + n i vo l u m a b ± BMS- 986207– s w i m m e r p l o t s Increase in response rate & duration suggest greater benefit with triplet Platinum-Resistant Standard of Care: Single agent chemo (ORR ~ 12%, mPFS ~3-4 months, mOS ~ 13 months, with significa
Slide 10: Clinical Vignette – COM701 + nivolumab partial response in nivolumab refractory PROC patient
C l i n i c a l V i g n ette – CO M 7 0 1 + n i vo l u m a b p a r t i a l re s p o n s e i n n i vo l u m a b ref ra c to r y P RO C p at i e nt Received 7 prior lines of therapy including progressed disease on nivolumab 53-year-old female with high grade serous Increased CD8+ T cell infiltration a
Slide 11: COM701 + nivolumab in MSS CRC cohort expansion
CO M 7 0 1 + n i vo l u m a b i n M S S C RC c o h o r t ex p a n s i o n Sw i m m e r p l o t MSS CRC Standard of Care 3L+: Regorafenib/Lonsurf (ORR ~ 1-2%, MPFS ~2 months, OS ~ 6-7months, with significant toxicity) 1,2 Investigator assessed responses 180 days 0.3/360 Q3WK Patient 3 C ESC 320+ 20/4
Slide 12: Extensive TME modulation in MSS CRC patients partially responding to COM701 + nivolumab
E x te n s i ve T M E m o d u l at i o n i n M S S C RC p at i e nt s p a r t i a l l y re s p o n d i n g to CO M 7 0 1 + n i vo l u m a b Increased CD8 infiltration and immune modulation Increased TCR clonality and clonal expansion Responder 1 Responder 1 Pre On Clone count 128 IFNg Most dominant
Slide 13: Compugen's immuno-oncology pipeline
C o m p u ge n ’s i m m u n o - o n c o l o g y p i p e l i n e Executing a unique combination approach PHASE PROGRAM INDICATION SPONSOR RECENT DEVELOPMENTS & (TARGET) Drug IND 2023 EXPECTED MILESTONES 1 POC 2 Discovery enabling Q1 2023 – First patient dosed COM701+ COM902 + Metastatic Microsatellit
Slide 14: Discussant
D isc ussant D r e w P a r d o l l , M . D . , P h . D . P r o f e s s o r o f O n c o l o g y, Johns Hopkins University and Chairman of Compugen's Scientific Advisory Board
Slide 15: Disclosures
Disclosures • Research support for PVRIG scientific research • Compugen SAB chair • No relevant IP • No personal equity in Compugen 15
Slide 16: Why block PVRIG together with TIGIT & PD-1?
Why block PVRIG together with TIGIT & PD-1? • PD-1 blockade foundational • PVRIG and TIGIT are parallel pathways so blocking only one leaves the other checkpoint intact • PVRIG and TIGIT are preferentially expressed on two populations of tumor-specific T cell that can give rise to activated effector
Slide 17: PVRIG PD1 TIGIT
Stem-memory PD1 2 key Teffector TIGIT T cell precursor PVRIG populations are Multi-checkpoint Activated Effector T cell restrained PD1 blockade Exhausted differently by key TIGIT T cell checkpoints PVRIG B16-F10 ID8-VEGF 17
Slide 18: Has TIGIT been a clinical failure? Does anti-TIGIT need to be Fc-active?
Has TIGIT been a clinical failure? Does anti-TIGIT need to be “Fc-active”? Answer: We don’t yet know Answer: Unclear but likely NOT • Roche trial – PFS curves not reported and OS has • Conflicting reports in mouse models – not read out. Furthermore, endpoint not necessarily Kuchroo/Anderson reported
Slide 19: Ovarian Cancer/MSS CRC great opportunities
Ovarian Cancer/MSS CRC great opportunities Ovarian Cancer MSS CRC • PD-1/TIGIT/PVRIG triple prioritizes potency • Some activity with PD-1/PVRIG doublet in a with 3 excellent mABs disease with an ORR to PD-1 blockade of <4% • Ovarian cancer has a decent lymphocyte • High unmet medical need so accrual