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

Transcription

1 FROM CODE TO CURE TM Corporate Overview November 217 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 forward-looking 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 Securities and Exchange Commission. 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 computational predictive discovery of novel targets 3

4 Overall Response Rate % MARKET OPPORTUNITY: 7-8% OF PATIENTS NON- RESPONSIVE TO APPROVED IMMUNOTHERAPIES ~2% Average Response Rate Gap to Bridge Approved indications In clinical testing TARGETING NEW IMMUNE CHECKPOINT PATHWAYS MAY ADDRESS NON-RESPONSIVE PATIENT POPULATION 4 4

5 KEY HIGHLIGHTS 1 Diversified pipeline of novel targets and therapeutic candidates Novel immune checkpoint targets including PVRIG, TIGIT and myeloid candidates Potential for PD-L1 non-responsive patients and/or for combination with existing therapies 2 3 Transitioning to a clinical stage company with lead asset PVRIG mab (COM71) IND expected towards end of Q1 218, Phase 1 open-label study to begin in 218 Synergy with both TIGIT and PD-1/L1 blockers Broadly applicable predictive discovery capabilities Continuous discovery of novel targets for internal development or collaborations Immune tolerance mechanism may represent next generation treatment for autoimmune diseases 4 World class scientific advisory team and collaboration partners Long term research collaborations with Johns Hopkins and Mount Sinai Development collaboration and license agreement with Bayer 5 5

6 COMPUGEN S PIPELINE PROGRAM From Code to Cure Target discovery Target validation mab discovery Screening/lead selection Cell line developmnt CMC/IND enabling IND Filing IMMUNO-ONCOLOGY COM71 / PVRIG end of Q1 218 CGEN-151T COM92 / TIGIT in 219 CGENXXXX / Myeloid Other programs AUTOIMMUNE CGEN Programs, from computer prediction to preclinical POC 6 6

7 BUILDING THE COMPUGEN IO PIPELINE: ADDING MULTIPLE MECHANISMS TO BROADLY ADDRESS CANCER TREATMENT COM71 Tumor/ APC PVRL2 DNAM PVR COM92 PVRIG TIGIT T Cell - PD-1 CGEN-XXXX PD-L1 Tumor/ APC ADDRESS VARIOUS IMMUNE SUPRESSIVE COMPONENT IN THE TME 7 7

8 APPLYING OUR PREDICTIVE APPROACH TO IMMUNE CHECKPOINT DISCOVERY CGEN novel targets A DISCOVERY ENGINE TO REPLENISH PIPELINE WITH NEW DRUG PROGRAMS 8 8

9 PVRIG BLOCKADE IS DIFFERENT FROM AND SYNERGISTIC WITH TIGIT BLOCKADE Separate inhibitory pathways Different temporal and spatial distribution of targets and ligands KEY FINDINGS PVRIG high T cell activation PVRIG is expressed in tumor microenvironment (CD8/TILs) Co-expressed in multiple tumor types with other checkpoints (TIGIT/PD-1) PVRIG ligand expressed in PD-L1 positive and negative tumors PVRIG-/- knockout mice have reduced tumor growth Potential monotherapy, dual and triple combination therapy with PD-1 and/or TIGIT blockers Martinet & Smyth, 215 (modified) 9 9 9

10 COM71: PVRIG CHECKPOINT INHIBITOR From Computer Prediction to Functional Activity in Preclinical Models COM71 is a high affinity humanized IgG4 mab targeting PVRIG PVRIG identified as a novel immune checkpoint by Compugen and plays a unique role in the validated TIGIT axis COM71 is synergistic with anti-tigit and PD-1 pathway blockers as a potential cancer immunotherapy treatment First-in-class opportunities as monotherapy and dual/triple combination therapies IND FILING EXPECTED TOWARDS THE END OF Q

11 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-PD-1 +/- ANTI-TIGIT 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-PD1 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 11 11

12 TUMOR GROWTH REDUCTION AND INCREASED SURVIVAL * * * WITH PVRIG AND PD-1 PATHWAY BLOCKADE CT26 syngeneic model Tumor growth Survival T im e 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 m m P e rc e n t s u rv i D a y s * * * p =. 5 ; T G I= 5 6 % m Ig G 1 + rig G 2 b 1 5 * p =. 4 4 ; T F = 4 /1 * 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 m m D a y s * * * p =. 5 ; T G I= 5 6 % 12 D a y s D a y s 12 12

13 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 KNOCK OUT 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 13 13

14 SYNERGISTIC REDUCTION IN TUMOR GROWTH TIGIT KNOCKOUT PLUS PVRIG BLOCKADE Tumor growth; B16 model 3 WT + migg1 WT + α-mpvrig m m B16-Dbgp1 model * 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 * p <.5 ANOVA 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 14 + α-mpvrig 63% 53% 49% 14 14

15 BIOLOGIC RATIONALE DRIVES COM71 CLINICAL DEVELOPMENT STRATEGY Tumor/ APC PVRL2 PVR DNAM PVRIG TIGIT T Cell - PD-1 PD-L1 Tumor/ APC INTERACTIONS OF THE PD-1 AND TIGIT/PVRIG PATHWAYS SUPPORT DRUG COMBINATION APPROACH 15 15

16 COM71 CLINICAL DEVELOPMENT STRATEGY Goal is to significantly expand the number of patients responsive to PD-1 blockade Targeting refractory and relapsing patient populations Potential to treat multiple patient populations based on expression Opportunities in lung, ovary, breast, endometrial, kidney, head & neck First-in-class opportunities as monotherapy and in combinations Biomarker strategy: enrich for patients most likely to respond Select patients with tumors where PVRIG, TIGIT pathways may be dominant Refractory & Relapsing Patients PD-L1 high Responsive Tumors (NSCLC, RCC) COM71 + PD-1 ± COM92 Naïve & Refractory & Relapsing Patients PD-L1 low/neg Poorly Responsive Tumors (Ovarian, TNBC, HNSCC) COM71 ± COM92 Naïve Patients PD-L1 low/neg Non-Responsive Tumors (MSS CRC) COM71 ± COM

17 STAGE 1C STAGE 1B STAGE 1A COM71 PHASE 1 CLINICAL STUDY COM71 Phase 1 First-in-man 3-stage design Oncology 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 17 17

18 COM92 COMBINATION WITH COM71 TIGIT identified as a putative immune checkpoint by Compugen s predictive discovery platform in 29 (N. Stanietsky et al PNAS 29) Potential best-in-class anti-tigit antibody, COM92, has high (femtomolar) binding affinity Combination of COM71 and COM92 antibodies provides potential unique clinical differentiation In vitro effects of TIGIT/PVRIG blockade equal or exceed those seen with PD-1 combinations Process development and manufacturing agreement with Bayer to produce COM92 COM92 CMC ACTIVITIES ONGOING; IND EXPECTED IN

19 TAPPING INTO THE WORLD OF MYELOID TARGETS The Next Wave of Cancer Immunotherapies COM71 Tumor/ APC PVRL2 DNAM PVR COM92 PVRIG TIGIT T Cell - PD-1 CGEN-XXXX PD-L1 Tumor/ APC TARGETING MYELOID BIOLOGY OFFER COMPLEMENTARY THERAPEUTIC APPROACHES TO CHECKPOINT INHIBITORS 19 19

20 MYELOID TARGETS: MULTIPLE MOAs FOR EFFICACY AND ANTI-TUMOR IMMUNE RESPONSE Myeloid biology blockade offers potential for efficacy in Patients with strong immunosuppressive tumor micro-environment ( cold tumors ) Patients refractory to available checkpoint inhibitors A limited number of programs in development for known targets CD47, SIRPα, CD4, CSF1R Myeloid Antibody MoA Cell Depletion NK 2 2

21 ** ** MYELOID TARGET EXAMPLE #1: CGEN-1532 KNOCKOUT REDUCES TUMOR GROWTH AND SUGGESTS MONOTHERAPY APROACH CGEN-1532 CGEN-1532 * P<.5 ** P<.1 46% TGI KO vs. WT 49% TGI rigg2b vs. PDL-1 43% TGI WT+ PD-L1 vs. KO+ PD-L1 Ganguly and Pardoll, Johns Hopkins Univ. MC38 model 21 21

22 Donor 2 Donor 1 MYELOID TARGET EXAMPLE #2: INHIBITS T CELL ACTIVATION SIMILAR TO PD-L1 CHO-S acd3 (OKT3) TCR Target #2 Counterpart + - T cells Target 2 Target 2 n=8 donors; p<.5 for CD4 & CD8 proliferation, IFN, TNFa and IL

23 MYELOID TARGET EXAMPLE #2: OPPORTUNITY TO TREAT PD-1 INHIBITOR RESISTANT PATIENT POPULATION Target 2 + Target 2 + Target 2 - Target 2 - % Samples 23 23

24 CANCER IMMUNOTHERAPY COLLABORATION WITH BAYER Collaboration and License Agreement, signed August 213 CGEN-151T - NOVEL IMMUNE CHECKPOINT From computer prediction to functional activity in preclinical models 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 24 for CGEN151T and CGEN

25 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 25 25

26 CGEN-151 DIFFERENTIATION AND VALUE PROPOSITION Addressing widely anticipated next step therapeutic revolution in autoimmunity Tolerance induction and restoration of immunologic homeostasis in immune diseases First-in-class therapeutic agent of a novel inhibitory checkpoint pathway Clinical and commercial opportunities in multiple autoimmune diseases 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 26 26

27 Number of Donor Tregs (x1 6 ) C lin ic a l S c o re CGEN-151: ROBUST EFFICACY IN MULTIPLE ANIMAL MODELS Short Term Treatment Consistently Leads to Durable Effect EAE: Multiple Sclerosis 3.5 Rx CIA: Rheumatoid Arthritis 6 P B S 5 C G E N E n b re l 4 NOD: Type 1 Diabetes Rx A rth ritis D a y Miller and Podojil, Northwestern Univ. Williams and McNamee, Univ. of Oxford, UK Miller and Podojil, Northwestern Univ. HY Mismatch: Bone Marrow Transplantation Number of Regulatory T cells in Spleen Miller and Podojil, Northwestern Univ. INTENTION TO PARTNER CGEN-151, TO FOCUS RESOURCES ON DEVELOPING IMMUNO-ONCOLOGY PRODUCTS 27 27

28 COMPUGEN: FOUR INTERNAL PROGRAM AREAS COM71 Anti-PVRIG mab drug candidate for cancer immunotherapy First-in-class advantage Novel checkpoint in TIGIT pathway Patent issued through Cancer Moonshot program Synergy with both -PD-1 and -TIGIT Myeloid Targets Complementary portfolio to T cell checkpoint programs for cancer immunotherapy Enhanced anti-tumor response through inhibition of immunosuppressive myeloid activity Multiple programs in progress COM92 Anti-TIGIT mab drug candidate for cancer immunotherapy Potential best-in-class mab with high (femtomolar) affinity Synergizes with COM71 and PD-1 pathways blockers CGEN-151 Fc fusion protein drug candidate for autoimmune diseases Unique immune tolerance mechanism Broadly applicable in RA, MS, T1D Durable response following short-term treatment in preclinical models 28 28

29 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 29 29

30 LEADERSHIP TEAM MANAGEMENT TEAM BOARD OF DIRECTORS Paul Sekhri Chairman of the Board Anat Cohen-Dayag, PhD President & CEO Ari Krashin Chief Financial & Operating Officer Kirk A. Christoffersen Senior VP - Corporate & Business Development Anat Cohen-Dayag, PhD President & CEO, Director 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 Joshua Shemer, MD Director 3 3

31 FINANCIAL POSITION Cash Balance Gross Cash Expenditures* Market Capitalization ~$153 million (October 217) $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) NBI (Nasdaq Biotech Index) TASE (CGEN.TA) TA-9, TA-125, TA-Biomed, TA Global BlueTech, TA Tech-Elite 31 31

32 FROM CODE TO CURE TM Corporate Overview November 217 Anat Cohen-Dayag, PhD President & CEO 32