FROM CODE TO CURE. Corporate Overview. January Anat Cohen-Dayag, PhD President & CEO.

Transcription

1 FROM CODE TO CURE TM Corporate Overview January 218 Anat Cohen-Dayag, PhD President & CEO 1

2 SAFE HARBOR STATEMENT This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of Forward-looking statements can be identified by the use of terminology such as will, may, expects, anticipates, believes, potential, plan, goal, estimate, likely, should, and intends, and describe opinions about possible future events. These forwardlooking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of Compugen to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Among these risks: Compugen s business model is substantially dependent on entering into collaboration agreements with third parties, and Compugen may not be successful in generating adequate revenues, or commercializing aspects of its business model. Compugen also may not meet expected milestones in its development pipeline. Moreover, the development and commercialization of therapeutic candidates involve many inherent risks, including failure to progress to clinical trials or, if they progress to or enter clinical trials, failure to receive regulatory approval. These and other factors, including the ability to finance the Company, are more fully discussed in the "Risk Factors" section of Compugen s most recent Annual Report on Form 2-F as filed with the Securities and Exchange Commission ( SEC ) as well as other documents that may be subsequently filed by Compugen from time to time with the SEC. In addition, any forward-looking statements represent Compugen s views only as of the date of this presentation and should not be relied upon as representing its views as of any subsequent date. Compugen does not assume any obligation to update any forward-looking statements unless required by law. Certain studies and data presented herein have been conducted for us by other entities as indicated where relevant. All intellectual property, including trade marks, trade names, slogan, logos, service marks, patents, copyrights or trade secret displayed in this presentation, including the name Compugen, are registered and unregistered intellectual property rights of Compugen. 2 2

3 FROM CODE TO CURE TM Our Vision Transforming patient lives by developing first-in-class therapeutics based on Compugen s foundational predictive target discovery and functional validation 3

4 KEY HIGHLIGHTS Diverse therapeutic pipeline based on original targets Immuno-oncology checkpoint programs: PVRIG, TIGIT, and myeloid candidates Next-generation immune tolerance induction autoimmune program Becoming a clinical stage company in 218 IND filing for COM71 (anti-pvrig mab) towards the end of Q1 Phase 1b study in COM71, monotherapy and combination therapy Proven target discovery capabilities and mab development expertise 4 programs, from computational discovery to preclinical POC Continuously generating original targets for earlier stage pipeline and collaborations World-class scientific advisory team and collaboration partners Immuno-oncology collaboration with Bayer Multi-year strategic collaborations with Johns Hopkins and Mount Sinai 4 4

5 COMPUGEN S PIPELINE From Code to Cure Target Discovery & Validation mab Discovery Preclinical Development Phase I IMMUNO-ONCOLOGY COM71 / PVRIG IND in Q1 218 CGEN-151T COM92 / TIGIT AUTOIMMUNE IND-enabling studies in 218; IND in 219 CGEN-151 IMMUNO-ONCOLOGY EARLY STAGE PIPELINE CGENXXXX / Myeloid Other programs 5 5

6 Overall Response Rate % MARKET OPPORTUNITY: 7-8% OF PATIENTS NON- RESPONSIVE TO APPROVED CANCER IMMUNOTHERAPIES ~2% Average Response Rate Gap to Bridge Approved indications In clinical testing TARGETING NEW PATHWAYS MAY ADDRESS NON-RESPONSIVE PATIENT POPULATIONS 6 6

7 ADDING MULTIPLE MECHANISMS TO BROADLY ADDRESS CANCER TREATMENT COM71 Tumor/ APC PVRL2 DNAM PVRIG + T Cell PD-1 PD-L1 Tumor/ APC PVR TIGIT 151T COM92 CGEN-XXXX 151T mab ADDRESSING MULTIPLE IMMUNE SUPRESSIVE COMPONENTS IN THE TME 7 7

8 LEADERSHIP TEAM MANAGEMENT TEAM BOARD OF DIRECTORS Paul Sekhri Chairman of the Board Anat Cohen-Dayag, PhD President & CEO, Director Anat Cohen-Dayag, PhD President and CEO Ari Krashin Chief Financial & Operating Officer Kirk Christoffersen SVP, Corporate & Business Development Yair Aharonowitz, PhD Director Ruth Arnon, PhD Director Zurit Levine, PhD VP, Research & Discovery John Hunter, PhD VP, Antibody R&D and Site Head Compugen USA, Inc. Yona Geffen, PhD VP, Research & Validation Martin S. Gerstel Director Dov Hershberg Director Arie Ovadia, PhD Director Tsipi Keren-Lehrer VP, Business Development Dorit Amitay VP, Human Resources Michal Preminger, PhD, MBA Director 8 8

9 KEY STRATEGIC ADVISORS Industry Veterans, Renowned Oncologists and Immunologists SCIENTIFIC ADVISORY BOARD Drew Pardoll, MD, PhD Chairman of the SAB Antoni Ribas, MD, PhD STRATEGIC ADVISORS Elliott Sigal, MD, PhD Former CSO, EVP and Director Multi-year strategic collaboration Charles Drake, MD, PhD Iain McInnes, MD, PhD Steven Holtzman President and CEO, Decibel Therapeutics Former CBO and CEO Miriam Merad, MD, PhD Multi-year strategic collaboration Howard Soule, PhD Richard Haiduck Former CBO and CEO Life science companies 9 9

10 COM71: PVRIG CHECKPOINT INHIBITOR CONFIDENTIAL 1

11 COM71: FIRST-IN-CLASS PVRIG CHECKPOINT INHIBITOR COM71 is a high-affinity humanized IgG4 mab targeting PVRIG PVRIG was computationally identified and validated by Compugen as an immune checkpoint target Shown to play a unique role in a PVRIG/TIGIT axis First-in-class opportunities for monotherapy and combination therapy in multiple solid tumor indications Strong clinical rationale for dual and triple combination with TIGIT and PD-1 pathway blockers Clinical opportunities in endometrial, ovarian, breast, lung, kidney, colorectal, and head & neck cancers Based on expression of the TIGIT and PVRIG and their ligands Shown to be safe at high doses in GLP toxicity study IND FILING EXPECTED TOWARDS THE END OF Q

12 COMPUGEN DISCOVERED AND VALIDATED PVRIG TARGET PVRIG BLOCKADE IS DIFFERENT FROM AND SYNERGISTIC WITH TIGIT BLOCKADE Martinet & Smyth, 215 (modified) 12 12

13 BIOLOGIC RATIONALE FOR COM71 CLINICAL COMBINATIONS Tumor/ APC PVRL2 PVR DNAM PVRIG TIGIT T Cell - PD-1 PD-L1 Tumor/ APC MOLECULAR INTERATIONS OF PD-1 AND TIGIT/PVRIG PATHWAYS SUPPORT DRUG COMBINATION APPROACH 13 13

14 IF N (p g /m L ) IF N (p g /m L ) IF N (p g /m L ) IF N (p g /m L ) ENHANCED T CELL ACTIVATION BY COM71 ALONE AND IN COMBINATION WITH ANTI-TIGIT +/- ANTI-PD-1 Anti-TIGIT combination T a r g e t C e ll: P a n c T u m o r c e lls T c e ll: C M V p p 6 5 s p e c ific C D 8 T c e lls Anti-PD-1 combination T a r g e t c e ll: C o lo 2 5 T u m o r c e lls T c e ll: C M V p p 6 5 s p e c ific C D 8 T c e lls Triple combination % % % % % % % % % % + 8 % % 1 1 h Ig G 4 C O M 7 1 T IG IT C O M T IG IT P D -1 h Ig G 4 C O M 7 1 T IG IT C O M T IG IT P D -1 h Ig G 4 C O M T IG IT C O M P D -1 T IG IT + P D -1 C O M T IG IT + P D -1 COM71 IN VITRO EFFECTS MATCH PD-1 INHIBITOR ASCO, June , Ophir, et al., poster presentation 14

15 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 ) 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 ) T u m o r v o lu m e (m m 3 ) TUMOR GROWTH REDUCTION IN PVRIG KNOCKOUT MICE ENHANCED IN COMBINATION WITH PD-1 PATHWAY BLOCKERS WT = wild type KO = knockout M C 3 8 W ild -ty p e v s 2 9 K O WT 5 M C 3 8 W ild -ty p e r Ig G 2 b PVRIG KO M C K O r Ig G 2 b W ild -ty p e r Ig G 2 b 2 9 K O r Ig G 2 b 4 3 D e a d 4 3 W ild -ty p e a n ti-p D L K O a n ti-p D L 1 2 D e a d 2 3 WT D a y s p o s t-tu m o r im p la n ta tio n 1 D e a d D a y s p o s t-tu m o r im p la n ta tio n 1 5 WT + anti-pd-l1 PVRIG KO PVRIG KO + anti-pd-l1 WT + anti-pd-l1 M C W ild -ty p e a n ti-p D L 1 PVRIG KO + anti-pd-l1 M C K O a n ti-p D L D a y s p o s t-tu m o r im p la n ta tio n D e a d 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 STIC, November , Hunter, et al., oral presentation 15

16 5 TUMOR GROWTH REDUCTION * AND * * INCREASED SURVIVAL WITH PVRIG AND PD-1 PATHWAY BLOCKADE T im e Tumor growth Survival V o lu m e m m 3 P e rc e n t s u rv iv a l V o lu m e P e rc e n t s u D a y s * * * p =. 5 ; T G I= 5 6 % 1 * p =. 4 4 ; T F = 4 / m Ig G 1 + rig G 2 b P D L -1 + rig G 2 b P D L m P V R IG T im e * * * * αpdl-1+rlgg2b αpdl-1+α-mpvrig m m D a y s D a y s m m D a y s * * * p =. 5 ; T G I= 5 6 % PVRIG/PVRL2 PATHWAY BIOLOGY IN MICE UNDERESTIMATED 16 COMPARED TO HUMANS, ANTICIPATING GREATER CT26 syngeneic THERAPEUTIC model EFFECT IN HUMANS STIC, November , Hunter, et al., oral presentation 16

17 SYNERGISTIC REDUCTION IN TUMOR GROWTH FROM TIGIT KNOCKOUT PLUS PVRIG BLOCKADE Tumor growth; B16 model 3 WT + migg1 WT + α-mpvrig m m B16-Dbgp1 model * * p <.5 ANOVA TIGIT KO + migg TIGIT KO + α-mpvrig 5 m m 3 m m D a y s m m 3 m m 3 3 D a y s D a y s D a y s D a y s W T + m Ig G 1 T IG IT K O + m Ig G 1 W T + -m P V R IG T IG IT K O + -m P V R IG TGI compared to WT + migg1 Day 11 Day 14 Day 18 WT+ α-mpvrig 17% 13% 8% TIGIT-KO + migg1 17% 17% 13% TIGIT-KO 17 + α-mpvrig 63% 53% 49% ASCO, June 217, Ophir, et al., poster presentation 17 17

18 BIOLOGIC RATIONALE DRIVES COM71 CLINICAL DEVELOPMENT STRATEGY Tumor/ APC PVRL2 PVR DNAM PVRIG TIGIT T Cell - PD-1 PD-L1 Tumor/ APC RECEPTOR/LIGAND EXPRESSION IN THE TME INFORMING PATIENT SELECTION BIOMARKER STRATEGY 18 18

19 COM71: BIOMARKER STRATEGY AND INITIAL DATA Goal is to select for patients most likely to respond to COM71, either alone or in combination Select patients with tumors in which PVRIG pathway may be dominant based on expression patterns Expression profiles of various axis components provide indication for a dominant role of the PVRIG/TIGIT axis multiple cancers PVRL2 is commonly upregulated in multiple tumor types Frequently expressed in PD-L1 negative tumors Expressed in PVR negative tumor and immune cell subpopulations in the TME PVRIG expressed on TILs and NK cells in the TME of multiple tumor types Majority of exhausted TILs in the tumor are PD-1, TIGIT and PVRIG positive 19 19

20 RELATIVE EXPRESSION OF PVRL2 VS PVR VARIES BY TUMOR TYPE TCGA RNA Analysis Higher PVR Higher PVRL2 HIGH PVRL2 EXPRESSION SUGGESTS PVRIG DOMINANCE; TUMOR CELLS FROM BREAST, OVARIAN, AND ENDOMETRIAL TUMORS ARE FREQUENTLY PDL1 NEG 2 Keystone, January 2 218, Ofir, et al., poster presentation 2

21 PVRL2 IS INDUCED IN THE TME AND EXPRESSED IN PD-L1 NEG TUMORS PVRL2 expression in PD-L1 - tumors Endometrioid Cancer Lung Adenocarcinoma SITC, November 217, Whelan, et al., poster presentation 21 21

22 COM71 CLINICAL DEVELOPMENT STRATEGY Goal is to target PD-1 pathway inhibitor refractory and relapsing patient populations Biomarker strategy to allow selection of tumors based on expression of pathway components Data support potential to treat multiple patient populations as monotherapy or combination therapy Opportunities in lung, ovary, breast, endometrial, kidney, and head & neck cancers Refractory & Relapsing Patients Naïve & Refractory & Relapsing Patients Anti-PD1 failures in approved indications (e.g. NSCLC, RCC) (COM71 + PD-1) ± COM92 PD1 refractory indications (e.g. Ovarian, TNBC, MSS CRC) (COM71) ± COM

23 STAGE 1C STAGE 1B STAGE 1A COM71 PHASE 1B CLINICAL STUDY TO BE INITIATED IN 218 Single agent, Simon 3x3 dose escalation Safety, tolerability, PK/PD, clinical activity All-comers trial; no pre-selection Progressed on SOC Maximum Tolerated Dose (MTD) COM71 in combination with anti-pd-1 Safety, tolerability, PK/PD, clinical activity Rolling delayed start, 1 level highest safe 1A dose Combined w/ fixed dose of anti-pd-1 Current PK data suggest every 3 week dosing Select expansion cohorts in specific indications 2-3 patients per cohort COM71 in combination with anti-pd-1 Monotherapy indications (pending 1a response) Safety, tolerability, PK/PD, clinical activity 23 23

24 ADDITIONAL IMMUNO-ONCOLOGY DEVELOPMENT PROGRAMS 24

25 COM92 ANTI-TIGIT MONOCLONAL ANTIBODY COM92 is a high-affinity (femtomolar) mab targeting TIGIT TIGIT identified as a putative immune checkpoint by Compugen s predictive target discovery platform in 29 (N. Stanietsky et al PNAS 29) Potential Best-in-Class In vitro activity comparable to or better than the top clinical TIGIT antibodies In vitro effects of TIGIT/PVRIG blockade equal or exceed those seen with PD-1 combinations Combination of COM71 and COM92 provides potential unique clinical differentiation IND-ENABLING ACTIVITIES IN 218; IND EXPECTED IN

26 I F N ( p g / m L ) IF N (p g /m L ) COM71 + COM92 POTENTLY ENHANCES TIL ACTIVATION Kidney CD3 TIL Endometrium CD3 TIL Ovarian CD3 TIL K i d n e y C D 3 + T I L EEnnd do om eet rt ri ui um CCD D TTI LI L O v a r ia n C D 3 + T IL I F N ( p g / m L ) % 6 8 % 5 % 8 3 % I F N ( p g / m L ) % 1 % 8 8 %% %% % % % % % 5 T c e l l s a l o n e h I g G 4 C O M 7 1 C O M 9 2 P e m b r o l i z u m a b C O M C O M 9 2 T c e l l s a l o n e T c e l l s a l o n e h I g G 4 h I g G 4 C O M 7 1 C O M 7 1 C O M 9 2 C O M 9 2 P e m b r o l i z u m a b P e m b r o l i z u m a b C O M C O M 9 2 C O M C O M 9 2 H 4 T c e lls a lo n e Is o ty p e C o n tr o l C O M 7 1 C O M 9 2 P e m b r o liz u m a b C O M C O M 9 2 SITC November 217, Whelan, et al., poster presentation; and Keystone, January 217, Ofir, et al., poster presentation 26 26

27 MYELOID TARGETS: MULTIPLE MOAs FOR EFFICACY AND ANTI-TUMOR IMMUNE RESPONSE Myeloid biology blockade offers potential for efficacy in Patients with strong immunosuppressive tumor microenvironment, or cold tumors Patients refractory to available checkpoint inhibitors Programs in development by various industry players CD47, SIRPα, CD4, CSF1R Myeloid Antibody MoA Cell Depletion NK 27 27

28 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 ) MYELOID TARGET EXAMPLE #1: CGEN-1532 KNOCKOUT REDUCES TUMOR GROWTH INDICATING ROLE IN TUMOR GROWTH REGULATION MC38 Wild-Type vs CGEN-1532 KO 4 W ild -ty p e 4 CGEN-1532 C G E N KO K O % TGI (p<.1) % TGI (p<.1) 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 CGEN-1532 KO Ganguly and Pardoll, Johns Hopkins Univ. MC38 model CRI, September 217, Levy, et al., poster presentation 28 28

29 Donor 2 Donor 1 MYELOID TARGET EXAMPLE #2: INHIBITS T CELL ACTIVATION SIMILAR TO PD-L1 n=8 donors; p<.5 for IFN, TNFa CHO-S acd3 (OKT3) TCR Target #2 Counterpart + - T cells Similar data obtained by measuring T cell proliferation inhibition 29 29

30 MYELOID TARGET EXAMPLE #2: OPPORTUNITY TO TREAT PD-1 INHIBITOR RESISTANT PATIENT POPULATIONS 3 3

31 CANCER IMMUNOTHERAPY COLLABORATION WITH BAYER Collaboration and License Agreement, signed August 213 CGEN-151T NOVEL IMMUNE CHECKPOINT Preclinical development on track Pivotal (GLP) toxicity studies ongoing GMP clinical trial material production ongoing $1M* upfront payment $15M Preclinical milestone payments to date Over $25M in potential milestone payments Royalties on global net sales: mid-to-high single digit * Received for CGEN151T and CGEN

32 AUTOIMMUNE PROGRAM CONFIDENTIAL 32

33 CGEN-151: FIRST-IN-CLASS THERAPEUTICS INDUCING TOLERANCE IN AUTOIMMUNE DISEASES CTLA4-lg (Orencia ) Fc fusion CGEN-151T mab CGEN-151 Fc fusion Compugen retained all rights to develop Fc fusions for autoimmune indications counterpart IMMUNE TOLERANCE MECHANISM REPRESENTS NEXT GENERATION TREATMENT FOR AUTOIMMUNE DISEASES 33 32

34 CGEN-151 DIFFERENTIATION AND VALUE PROPOSITION Addressing widely anticipated next step therapeutic revolution in autoimmunity Tolerance induction and restoration of immunologic homeostasis First-in-class therapeutic agent of a novel inhibitory checkpoint pathway Robust efficacy in multiple animal models, presenting clinical and commercial opportunities in multiple autoimmune diseases Short term treatment leads to durable effect Paradigm shift from standard of care Tolerance induction offers safety advantages vs. immune-suppression Potentially efficacious in patients with inadequate response to standard of care INTENTION TO PARTNER CGEN-151, TO FOCUS RESOURCES ON DEVELOPING IMMUNO-ONCOLOGY PRODUCTS 34 34

35 PREDICTIVE TARGET DISCOVERY & FUNCTIONAL VALIDATION CAPABILITIES CONFIDENTIAL 35

36 APPLYING OUR PREDICTIVE APPROACH TO TARGET DISCOVERY AND FUNCTIONAL VALIDATION Genome & Proteome Analysis Research reagents preparation Biological knowledge Model Test Refine Functional in vitro analysis Expression profiles Therapeutic Development Experimental & Disease Data Functional in vivo analysis (KO/surrogate mab) Computational Discovery Target Validation A DISCOVERY ENGINE TO REPLENISH PIPELINE WITH NEW DRUG PROGRAMS 36 36

37 FINANCIAL POSITION Cash Balance Gross Cash Expenditures* Market Capitalization ~$15 million (January 218) $38.5 million (September 3, 217) No Debt ~$8.5 million/quarter 217 quarterly forecast * Does not include cash receipts from any source. NASDAQ (CGEN) TASE (CGEN.TA) SME-15, TA-Biomed, TA Global BlueTech, TA Tech-Elite 37 37

38 CURRENT AND UPCOMING ANTICIPATED MILESTONES Becoming a clinical stage company in 218 COM71 (anti-pvrig mab) - IND filing anticipated towards the end of Q1 218 Phase 1b study monotherapy and combination with PD-1 pathway blockade CGEN-151T mab (Bayer) - currently in IND-enabling studies Advancing preclinical pipeline COM92 (anti-tigit mab) - IND-enabling studies in 218; IND expected in 219 Various myeloid programs progressing towards preclinical development Multiple programs progressing through validation 38 38

39 FROM CODE TO CURE TM Thank you January 218 Anat Cohen-Dayag, PhD President & CEO 39