Corporate Overview. February Anat Cohen-Dayag, PhD President & CEO.

Transcription

1 Corporate Overview February 2019 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 or delay to progress to clinical trials or, if they progress to or enter clinical trials, failure to advance through clinical development or 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 20-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. Intellectual property, including patents, copyrights or trade secret displayed in this presentation, whether registered or unregistered, are the intellectual property rights of Compugen. Compugen's name and logo and other Compugen product names, slogans and logos referenced in this presentation are trademarks of Compugen Ltd. and/or its subsidiaries, registered in the U.S.A., EU member states and Israel. 2 2

3 FROM CODE TO CURE Our Vision Transforming patient lives by developing first-in-class therapeutics based on Compugen s computational target discovery platform 3 3

4 Hodgkin's lymphoma Melanoma Ipi/Nivo NSCLC (Sq+chemo) (1L) NSCLC (Non-Sq MSI-High CSCC NSCLC Mono (1L >50%) RCC Ipi/Nivo (1L) CRC MSI Melanoma Merkel Cell Bladder (1L) RCC (2L) NSCLC (2L) HCC H&N Cervical Cancer Gastric SCLC Endometrial MSS Mesothelioma Ovarian TNBC Breast Cancer CRC MSS Pancreatic Prostate Overall response Rate % SIGNIFICANT UNMET NEED: 70-80% OF PATIENTS NON- RESPONSIVE TO APPROVED CANCER IMMUNOTHERAPIES ~20-30% Average Response Rate In clinical testing PD-1 blockers approved indications Our value proposition and differentiated approach: New targets aimed towards non-responsive patient populations Mechanistic-driven first-in-class combinations Robust biomarker strategy to select patients based on pathway expression profile COMPUGEN IS TARGETING NOVEL PATHWAYS TO ADDRESS NON-RESPONSIVE PATIENT POPULATIONS 4 4

5 KEY INVESTMENT HIGHLIGHTS Innovative I/O Portfolio Strategic Collaborations Proven Computational Platform First-in-class Phase 1 drug candidates COM701, BAY Novel immune checkpoints and immunomodulatory targets Corporate partners: R&D collaborations: Johns Hopkins, Mount Sinai Established engine for novel drug programs Purpose-built algorithmic analyses Integrated I/O and drug development expertise 5 5

6 COMPUGEN S PIPELINE From Code to Cure PROGRAM IMMUNO-ONCOLOGY COM701 anti-pvrig antibody COM701 + Opdivo * anti-pvrig antibody + anti-pd-1 antibody PARTNER DISEASE DRUG DISCOVERY PRECLINICAL DEVELOPMENT PHASE 1 All comers; expansion to Lung, Breast, Ovarian, Endometrial Lung, Breast, Ovarian, Endometrial BAY anti-ildr2 antibody Undisclosed COM902 anti-tigit antibody IND planned for 2019 Bi-specific products U N D I S C L O S E D Multiple myeloid programs AUTOIMMUNE CGEN ILDR2-Fc * Collaboration is designed to address potential future combinations, including trials sponsored by Bristol-Myers Squibb to investigate combined inhibition of checkpoint mechanisms, such as PVRIG & TIGIT Compugen-owned program Partnered programs 6 6

7 INNOVATIVE IMMUNO-ONCOLOGY PORTFOLIO 7 7

8 COM701: FIRST-IN-CLASS DRUG OPPORTUNITY IN NON- RESPONSIVE TUMOR TYPES COM701: a high-affinity humanized IgG4 mab targeting PVRIG PVRIG novel immune checkpoint pathway discovered by Compugen s computational platform; part of the DNAM axis Clinical opportunities in tumor types with high unmet need, such as endometrial, ovarian, breast, lung and other solid tumors PVRIG is broadly expressed in both PD-L1 + and PD-L1 - tumors Rationale for combination strategy based on deep understanding of DNAM axis Dual and triple combination with TIGIT and PD-1 inhibitors Robust biomarker-driven strategy and rationale based on elevated expression of axis members Strong IP position 8 8

9 Advanced Cancer patients COM701 ADDRESSES HIGH UNMET NEED IN MAJOR MARKET CANCER INITIAL INDICATIONS NSCLC 160,000 Leading cause of cancer death Large opportunity in PD-1 R/R population ( 2L) Chemo ORR of ~10% Ovarian 43,000 No approved PD-1 Significant unmet need in 3L Chemo ORR of 8-15% Breast 70,000 No approved PD-1 Limited benefit seen w/ PD-1 in HR+/Her2- Modest benefit seen w/ PD-1 mono in TNBC (~10% ORR) Significant unmet need in advanced patient populations Endometrial 25,000 No approved targeted therapies Significant unmet need in 2L MSS Chemo ORR of 10% Total 298,000 FUTURE EXPANSION OPPORTUNITIES IN ADDITIONAL INDICATIONS & EARLIER LINES OF THERAPY Source: Decision Resources 9 9

10 PVRIG IS A NOVEL CHECKPOINT IN THE TIGIT/DNAM AXIS: TWO PARALLEL INHIBITORY PATHWAYS T CELL / NK Cell Martinet & Smyth, 2015 (modified) 10 10

11 DNAM INTERSECTS WITH THE PD-1 PATHWAY AND IS REQUIRED FOR IN VIVO RESPONSE TO PD-1 INHIBITORS PD-1 inhibition blocks DNAM (CD226) dephosphorylation and inactivation DNAM KO or inhibition reverses anti-pd1 + anti-gitr tumor growth inhibition anti-dnam DNAM KO Wang et al., Science Immunology,

12 PVRIG PATHWAY: A SUGGESTED MECHANISM OF RESISTANCE IN PD-1 INHIBITOR NON-RESPONSIVE TUMORS COM701 Tumor/ APC PVRL2 DNAM PVR PVRIG TIGIT T Cell - PD-1 PD-L1 Tumor/ APC COM902 THE DNAM AXIS: POTENTIAL MOLECULAR INTERACTIONS OF PD-1 AND TIGIT/PVRIG PATHWAYS SUPPORT DRUG COMBINATION APPROACH 12 12

13 COM701 PHASE 1 CLINICAL STUDY INITIATED SEPT 2018 ClinicalTrials.gov Identifier: NCT Phase 1a Phase 1b Study objectives Arm A COM701 Monotherapy Dose escalation (Hybrid accelerated titration design with 3+3 design) All comers (progressed on SOC) COM701 Monotherapy Cohort Expansion (20 patients; progressed on SOC) NSCLC Ovarian Dual Combination (COM701 + Opdivo) Expansion (~20 patients/cohort) NSCLC Ovarian Safety & Tolerability PK/PD Clinical activity - COM701 monotherapy and in combination with Opdivo Breast Breast Endometrial Endometrial Arm B Biomarker strategy Dual combination (Escalating doses of COM701 with fixed dose of Opdivo) All comers Expression of DNAM axis members. Additional indications based on biomarker analysis

14 TARGET INDICATIONS EXPRESS HIGHER PVRL2 RELATIVE TO PVR SUGGESTING MONOTHERAPY POTENTIAL Monotherapy and Combination Potential PVRL2 PVRIG RNA (TCGA database) NSCLC #1 NSCLC #

15 PVRL2 IS COMMONLY EXPRESSED IN PD-L1 NEGATIVE TUMORS Opportunity to Treat PD-1 Inhibitor Relapsed/Refractory Tumors PVRL2 PD-L1 Endometrioid Cancer Lung Adenocarcinoma SITC, November 2017, Whelan, et al., poster presentation 15 15

16 COM701 INCREASES T CELL ACTIVATION Synergistic Effect in Combination With Other Checkpoint Inhibitors COM701 +/- anti-tigit COM701 +/- anti-pd1 Triple combination ASCO, June 2017, Ophir, et al., poster presentation 16 16

17 PVRIG ABLATION/INHIBITION REDUCES TUMOR GROWTH IN MOUSE CANCER MODELS PVRIG KO MICE (MC38) anti-pvrig + anti-pd1 (CT26) anti-pvrig + TIGIT KO (B16) WT KO WT + αpdl-1 KO + αpdl-1 Control IgG apdl-1 apdl-1+a-mpvrig Reduced tumor growth in KO mice Synergistic tumor growth inhibition with anti-pd1 PVRIG inhibition required for tumor growth inhibition in TIGIT KO mice Ganguly and Pardoll, Johns Hopkins Univ. MC38 model SITC, November 2016, Hunter, et al., oral presentation 17 17

18 COM902 ANTI-TIGIT PROGRAM DESIGNED TO MAXIMIZE COM701 CLINICAL POTENTIAL Potential best-in-class TIGIT antibody A high-affinity (femtomolar) mab In vitro activity comparable to or better than the top clinical TIGIT antibodies Preclinical data demonstrates parallel PVRIG and TIGIT inhibition enhances tumor growth inhibition Combination of COM902 & COM701 offers unique clinical differentiation in tumors that are non-responsive to approved checkpoint inhibitors IND filing planned for

19 MYELOID PROGRAMS OUR NEXT WAVE OF I/O PROGRAMS Multiple programs at various stages of research and development Myeloid Antibody MoA Cell Depletion NK

20 CGEN-15001: FIRST-IN-CLASS THERAPEUTICS INDUCING IMMUNE TOLERANCE IN AUTOIMMUNE DISEASES BAY /anti-ILDR2 mab CTLA4-lg (Orencia ) Fc fusion CGEN Fc fusion Compugen retained all rights to develop Fc fusions for autoimmune indications counterpart PRECLINICAL PROOF OF CONCEPT; INTENTION TO PARTNER 20 20

21 STRATEGIC COLLABORATIONS 21

22 CLINICAL COLLABORATION WITH BRISTOL-MYERS SQUIBB Clinical Trial Collaboration and Equity Investment, signed October 2018 Bristol-Myers Squibb to supply Opdivo for Compugen s Phase 1 dual combination arm of COM701 and Opdivo Framework for expansion to additional combination studies, such as PVRIG and TIGIT blockers Broad assessment of COM701 in patients non-responsive to immunotherapy Potential to accelerate clinical development timelines for COM701 Compugen retains ownership and commercial rights of COM701 Bristol-Myers Squibb has right-of-first negotiation during exclusivity period $12 million strategic investment, hold ~4% ownership in Compugen

23 DEVELOPMENT & COMMERCIALIZATION AGREEMENT WITH BAYER Collaboration and License Agreement, signed August 2013 BAY first-in-class therapeutic antibody program targeting ILDR2 ILDR2 a novel immune checkpoint discovered by Compugen computational platform Phase 1 first patient dosed September 2018 Preclinical data for BAY demonstrate unique mechanism of action with broad combination potential $Over $30M* in upfront and milestone payments to date Over $250M in potential future milestone payments Royalties on global net sales: mid-to-high single digit * CGEN15001T and CGEN

24 LICENSE AGREEMENT WITH ASTRAZENECA Signed March 2018 Development of bi-specific and multi-specific immunooncology antibody products Based on one pipeline program AstraZeneca has the right to create multiple products and is responsible for research, development and commercial activities Compugen retains full rights to all of its pipeline programs: As monotherapies and in combination with other products For the development of bi-specific and multi-specific programs, with the exception of the rights licensed to AstraZeneca $10M Upfront payment Up to $200M Milestone payments for first product Milestone payments on each additional products Tiered royalties on future products sales 24 24

25 COMPUTATIONAL DISCOVERY PLATFORM & NEXT WAVE OF NEW IMMUNO-ONCOLOGY PROGRAMS 25 25

26 Clinical hypothesis Refined datasets Output APPLYING OUR PREDICTIVE APPROACH TO TARGET DISCOVERY Expert integration of multi-omics data Analysis across multiple proprietary platforms RNASeq (Cancer/Normal) Immune cells Genomic Structure Differential Correlation Novel target Identification Transcriptome and proteome Clinical Samples Single Cell analysis Patient stratification Model Test Refine New therapy solutions Single cell Proteomics microarray Differential expression Survival analysis Integrated expert review Computational Immuno-oncology Drug development Clinical MORE THAN 80 PEER-REVIEWED PAPERS DEMONSTRATING COMPUTATIONAL DISCOVERY POWER 26 26

27 Clinical hypothesis Refined datasets Output APPLYING OUR PREDICTIVE APPROACH TO DISCOVER NOVEL IMMUNE CHECKPOINTS Expert integration of multi-omics data Analysis across multiple proprietary platforms Purpose-built Platform: Algorithmic identification of ICP genes with conserved structures RNASeq (Cancer/Normal) Immune cells Genomic Structure Differential Correlation Transcriptome and proteome Clinical Samples Single Cell analysis Patient stratification Model Test Refine TIGIT ILDR2 PVRIG Others Single cell microarray Differential expression Survival analysis Proteomics 27 27

28 PROVEN PREDICTIVE DISCOVERY ENGINE IS POWERING NEXT WAVE OF NEW I/O PROGRAMS Dendritic cell activation & antigen presentation TAM depletion/reprogramming PD-1 inhibitor resistance T & NK cell activation 28 28

29 FINANCIAL POSITION Cash Balance ~$46 million (December 31, 2018) No Debt Gross Cash Expenditures* 2019 annual forecast ~$27-29 million Market Capitalization ~$200 million (February 2019) NASDAQ (CGEN) TASE (CGEN.TA) SME-150, TA-Biomed, TA Global BlueTech, TA Tech-Elite * Includes one-time restructuring related costs; excludes cash receipts from any source 29 29

30 2018 ACCOMPLISHMENTS AND FUTURE VALUE DRIVERS 2018 Accomplishments Future Value Drivers COM701 IND filing and Phase 1 initiation BAY IND filing, Phase 1 initiation and milestone payment from Bayer Bristol-Myers Squibb COM701 clinical collaboration and equity investment AstraZeneca bispecific license agreement Validation of the computational platform 2 programs from computer prediction of a novel drug target to clinical development 2 preclinical programs COM701 Phase 1 study Initiation of Arm B (escalating doses of COM701 with fixed doses of Opdivo) in Q Completion of enrollment for the monotherapy and dual combination dose escalation arms in second half of 2019 COM902 IND filing Partnered products Continued BAY development AstraZeneca product development Advancement of next wave of I/O programs 30 30

31 KEY INVESTMENT HIGHLIGHTS Innovative I/O Portfolio Strategic Collaborations Proven Computational Platform First-in-class Phase 1 drug candidates COM701, BAY Novel immune checkpoints and immunomodulatory targets Corporate partners: R&D collaborations: Johns Hopkins, Mount Sinai Established engine for novel drug programs Purpose-built algorithmic analyses Integrated I/O and drug development expertise 31 31

32 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 Jean-Pierre Bizzari, MD Director Henry Adewoye, MD Chief Medical Officer John Hunter, PhD Chief Scientific Officer Zurit Levine, PhD SVP, Technology Innovation Gilead Halevy Director Kinneret Livnat Savitzky, PhD Director Arie Ovadia, PhD Director Riki Schwartz VP, Research and Discovery Dorit Amitay VP, Human Resources Sanford (Sandy) Zweifach Director 32 32

33 STRATEGIC ADVISORS Industry Veterans, Renowned Oncologists and Immunologists SCIENTIFIC ADVISORY BOARD BUSINESS ADVISORS Drew Pardoll, MD, PhD Chairman of the SAB Antoni Ribas, MD, PhD 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 33 33

34 FROM CODE TO CURE TM Thank you February 2019 Anat Cohen-Dayag, PhD President & CEO 34