Corporate Overview - Compugen...This presentation contains “forward-looking statements” within...
Transcript of Corporate Overview - Compugen...This presentation contains “forward-looking statements” within...
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FROM CODE TO CURE
CorporateOverview
www.cgen.com
January 2019
Anat Cohen-Dayag, PhD
President & CEO
TM
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SAFE HARBOR STATEMENTThis presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of
1995. 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 or delay 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 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.
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, whether registered or unregistered intellectual property rights of Compugen.
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Transforming patient lives by
developing first-in-class therapeutics
based on Compugen’s computational
target discovery platform
Our Vision
FROM CODE TO CURE TM
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%SIGNIFICANT UNMET NEED: 70-80% OF PATIENTS NON-RESPONSIVE TO APPROVED CANCER IMMUNOTHERAPIES
~20-30% Average Response Rate
PD-1 blockers approved indications
In clinical testing
COMPUGEN IS TARGETING NOVEL PATHWAYS TO ADDRESS NON-RESPONSIVE PATIENT POPULATIONS
Our value proposition and differentiated approach:
• New targets aimed towards non-responsive patient populations
• Mechanistic-driven first-in-classcombinations
• Robust biomarker strategy to select patients based on pathway expression profile
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KEY INVESTMENT HIGHLIGHTS
Innovative I/O
Portfolio
• First-in-class Phase 1 drug candidates
• COM701, BAY 1905254
• Novel immune checkpoints and immunomodulatory targets
Proven
Computational
Platform
• Established engine for novel drug programs
• Purpose-built algorithmic analyses
• Integrated I/O and drug development expertise
Strategic
Collaborations
• Corporate partners:
• R&D collaborations:Johns Hopkins, Mount Sinai
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COMPUGEN’S PIPELINEFrom Code to Cure™
* 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
IMMUNO-ONCOLOGY
COM701
anti-PVRIG antibody
DISEASE DRUG DISCOVERY PRECLINICAL DEVELOPMENT PHASE 1 PROGRAM
COM701 + Opdivo® *
anti-PVRIG antibody + anti-PD-1 antibody
BAY 1905254
anti-ILDR2 antibody
COM902
anti-TIGIT antibody
Bi-specific products
Multiple myeloid programs
AUTOIMMUNE
CGEN-15001
ILDR2-Fc
P1 initiation planned for 2019
PARTNER
U N D I S C L O S E D
Compugen-owned program Partnered programs
All comers; expansion
to Lung, Breast,
Ovarian, Endometrial
Lung, Breast, Ovarian,
Endometrial
Undisclosed
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INNOVATIVE IMMUNO-ONCOLGY PORTFOLIO
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• 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
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COM701: FIRST-IN-CLASS DRUG OPPORTUNITY IN NON-RESPONSIVE TUMOR TYPES
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COM701 ADDRESSES HIGH UNMET NEED IN MAJOR MARKET CANCER INITIAL INDICATIONS
FUTURE EXPANSION OPPORTUNITIES IN ADDITIONAL INDICATIONS & EARLIER LINES OF THERAPY
• Leading cause of cancer death
• Large opportunity in PD-1 R/R population (≥2L)
• Chemo ORR of ~10%
• No approved PD-1• Significant unmet
need in ≥3L• Chemo ORR of 8-15%
• 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
• No approved targeted therapies
• Significant unmet need in ≥2L MSS
• Chemo ORR of 10%
NSCLCOvarian
BreastEndometrial Total
Source: Decision Resources
298,000
70,000
43,000
160,000
Ad
van
ced
Can
cer
pat
ien
ts 25,000
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PVRIG IS A NOVEL CHECKPOINT IN THE TIGIT/DNAMAXIS: TWO PARALLEL INHIBITORY PATHWAYS
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Martinet & Smyth, 2015 (modified)
T CELL / NK Cell
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DNAM INTERSECTS WITH THE PD-1 PATHWAY AND IS REQUIRED FOR IN VIVO RESPONSE TO PD-1 INHIBITORS
Wang et al., Science Immunology, 2018
DNAM KO
anti-DNAM
PD-1 inhibition blocks DNAM (CD226) dephosphorylation and inactivation
DNAM KO or inhibition reverses anti-PD1 + anti-GITR tumor growth inhibition
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+Tumor/
APC
-
-
PVRIG
DNAM
TIGIT
PVRL2
PVR
-
PD-1 PD-L1
Tumor/
APC
T Cell
THE DNAM AXIS: POTENTIAL MOLECULAR INTERACTIONS OF PD-1 AND TIGIT/PVRIG PATHWAYS SUPPORT DRUG COMBINATION APPROACH
PVRIG PATHWAY: A SUGGESTED MECHANISM OF RESISTANCE IN PD-1 INHIBITOR NON-RESPONSIVE TUMORS
COM701
COM902
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COM701 PHASE 1 CLINICAL STUDY – INITIATED SEPT 2018ClinicalTrials.gov Identifier: NCT03667716
Phase 1bPhase 1a Study objectives
Safety & Tolerability
PK/PD
Clinical activity - COM701 monotherapy and in combination with Opdivo
Expression of DNAM axis members. Additional indications based on biomarker analysis.
Biomarker strategy
Breast
NSCLC
Ovarian
Endometrial
All comers (progressed on SOC)
Breast
NSCLC
Ovarian
Endometrial
Dual combination(Escalating doses of COM701 with fixed dose of Opdivo)
COM701 MonotherapyCohort Expansion(20 patients; progressed on SOC)
COM701 MonotherapyDose escalation(Hybrid accelerated titration design with 3+3 design)
All comers
Dual Combination (COM701 + Opdivo) Expansion(~20 patients/cohort)
Arm A
Arm B
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TARGET INDICATIONS EXPRESS HIGHER PVRL2 RELATIVE TO PVR SUGGESTING MONOTHERAPY POTENTIALMonotherapy and Combination Potential
PVRL2 PVRIGRNA (TCGA database)
NSCLC #1
NSCLC #2
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PVRL2 IS COMMONLY EXPRESSED IN PD-L1 NEGATIVE TUMORSOpportunity to Treat PD-1 Inhibitor Relapsed/Refractory Tumors
SITC, November 2017, Whelan, et al., poster presentation
LungAdenocarcinoma
EndometrioidCancer
PVRL2 PD-L1
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COM701 INCREASES T CELL ACTIVATIONSynergistic Effect in Combination With Other Checkpoint Inhibitors
COM701 +/- anti-TIGIT COM701 +/- anti-PD1 Triple combination
ASCO, June 2017, Ophir, et al., poster presentation
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PVRIG ABLATION/INHIBITION REDUCES TUMOR GROWTH IN MOUSE CANCER MODELS
Ganguly and Pardoll, Johns Hopkins Univ. MC38 model
PVRIG KO MICE (MC38) anti-PVRIG + anti-PD1 (CT26) anti-PVRIG + TIGIT KO (B16)
Control IgG
aPDL-1
aPDL-1+a-mPVRIG
WT
KO
WT + αPDL-1
KO + αPDL-1
Reduced tumor growth in KO mice Synergistic tumor growth inhibition with anti-PD1
PVRIG inhibition required for tumor growth inhibition in TIGIT KO mice
SITC, November 2016, Hunter, et al., oral presentation
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INITIATION OF COM902 PHASE 1 EXPECTED IN 2019
• 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 inhibitionenhances tumor growth inhibition
• Combination of COM902 & COM701 offers unique clinical differentiation in tumors that are non-responsive to approved checkpoint inhibitors
COM902 ANTI-TIGIT PROGRAM DESIGNED TO MAXIMIZE COM701 CLINICAL POTENTIAL
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MYELOID PROGRAMS – OUR NEXT WAVE OF I/O PROGRAMS
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Antibody MoA –
Cell Depletion
NK
Myeloid
Multiple programs at various stages of research and development
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CGEN-15001: FIRST-IN-CLASS THERAPEUTICS INDUCING IMMUNE TOLERANCE IN AUTOIMMUNE DISEASES
PRECLINICAL PROOF OF CONCEPT; INTENTION TO PARTNER
Fc fusion
CTLA4-lg(Orencia®)
Fc fusionCGEN-15001
BAY 1905254/anti-ILDR2 mAb
Compugen retained all rights to develop Fc fusions for autoimmune indications
counterpart
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STRATEGIC COLLABORATIONS
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CLINICAL COLLABORATION WITH BRISTOL-MYERS SQUIBBClinical Trial Collaboration and Equity Investment, signed October 2018
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• 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
• Bristol-Myers Squibb has right-of-first negotiation during exclusivity period
• Compugen retains ownership and commercial rights of COM701
• $12 million strategic equity investment, representing ~4% ownership in Compugen
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DEVELOPMENT & COMMERCIALIZATION AGREEMENT WITH BAYER Collaboration and License Agreement, signed August 2013
BAY 1905254 – first-in-class therapeutic antibody program targeting ILDR2
• ILDR2 – a novel immune checkpoint discovered by Compugen computationalplatform
• Phase 1 – first patient dosed September 2018
• Preclinical data for BAY 1905254 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-15022
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LICENSE AGREEMENT WITH MEDIMMUNESigned March 2018
Development of bi-specific and multi-specific immuno-oncology antibody products
• Based on one pipeline program
• MedImmune 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 MedImmune
$10MUpfront payment
Up to $200MMilestone payments for first product
Milestone payments on each additional products
Tiered royalties on future products sales
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COMPUTATIONAL DISCOVERY PLATFORM & NEXT WAVE OF NEW I/O PROGRAMS
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Differential Correlation
Patient stratificationSingle Cell analysis
RNASeq(Cancer/Normal)
Proteomics
Genomic Structure
Clinical SamplesModel
TestRefine
APPLYING OUR PREDICTIVE APPROACH TO TARGET DISCOVERY
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Immune cells
Differential expression Survival analysis
Single cell microarray
Transcriptome and proteome
Novel target Identification
New therapy solutions C
linic
al h
ypo
the
sis
Expert integration ofmulti-omics data Analysis across multiple
proprietary platforms
Integrated expert review• Computational• Immuno-oncology• Drug development• Clinical
MORE THAN 80 PEER-REVIEWED PAPERS DEMONSTRATING COMPUTATIONAL DISCOVERY POWER
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Differential Correlation
Patient stratificationSingle Cell analysis
RNASeq (Cancer/Normal)
Proteomics
Genomic Structure
Clinical SamplesModel
TestRefine
APPLYING OUR PREDICTIVE APPROACH TO DISCOVER NOVEL IMMUNE CHECKPOINTS
Immune cells
Differential expression Survival analysis
Single cell microarray
Transcriptomeand proteome
TIGITILDR2PVRIGOthers…
Clin
ical
hyp
oth
esi
s
Expert integration ofmulti-omics data Analysis across multiple
proprietary platforms
Purpose-built Platform: Algorithmic identification of ICP genes with conserved structures
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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
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FINANCIAL POSITION
Gross Cash Expenditures*
Market Capitalization
$34.9 million*
(September 30, 2018)
No Debt
~$150 million (December 2018)
NASDAQ (CGEN)
TASE (CGEN.TA)SME-150, TA-Biomed, TA Global
BlueTech, TA Tech-Elite
• Does not include cash receipts from any source
Cash Balance
~$9-10 million/quarter 2018 quarterly forecast
* Does not include $7.8M milestone payment from Bayer and $12M equity investment by BMS
A
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2018 ACCOMPLISHMENTS AND FUTURE VALUE DRIVERS
• COM701 IND filing and Phase 1 initiation
• BAY 1905254 IND filing, Phase 1 initiation and milestone payment from Bayer
• Bristol-Myers Squibb COM701 clinical collaboration and equity investment
• MedImmune bispecific license agreement
• Validation of the computational platform
• 2 programs from computer prediction of a novel drug target to clinical development
• 2 programs in preclinical development
• Multiple COM701 data readouts
• Monotherapy safety data
• COM701 + Opdivo® combination data
• Monotherapy & combination expansion cohorts
• COM902 IND filing and phase 1 initiation
• Partnered products
• Continued BAY 1905254 development
• MedImmune product development
• Advancement of next wave of I/O programs
2018 Accomplishments Future Value Drivers
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KEY INVESTMENT HIGHLIGHTS
Innovative I/O
Portfolio
• First-in-class Phase 1 drug candidates
• COM701, BAY 1905254
• Novel immune checkpoints and immunomodulatory targets
Proven
Computational
Platform
• Established engine for novel drug programs
• Purpose-built algorithmic analyses
• Integrated I/O and drug development expertise
Strategic
Collaborations
• Corporate partners:
• R&D collaborations:Johns Hopkins, Mount Sinai
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LEADERSHIP TEAM
BOARD OF DIRECTORSMANAGEMENT TEAM
Paul SekhriChairman of the Board
Anat Cohen-Dayag, PhD President & CEO, Director
Yair Aharonowitz, PhDDirector
Gilead HalevyDirector
Sanford (Sandy) ZweifachDirector
Kinneret Livnat Savitzky, PhDDirector
Anat Cohen-Dayag, PhD President and CEO
Ari KrashinChief Financial & Operating Officer
Kirk ChristoffersenSVP, Corporate & Business Development
John Hunter, PhDChief Scientific Officer
Zurit Levine, PhDSVP, Technology Innovation
Henry Adewoye, MD Chief Medical Officer
Arie Ovadia, PhDDirector
Jean-Pierre Bizzari, MDDirector
Dorit AmitayVP, Human Resources
Riki SchwartzVP, Research and Discovery
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BUSINESS ADVISORSSCIENTIFIC ADVISORY BOARD
Elliott Sigal, MD, PhDFormer CSO, EVP and Director
Richard HaiduckFormer CBO and CEO Life science companies
Charles Drake, MD, PhD
Howard Soule, PhD
Iain McInnes, MD, PhD
STRATEGIC ADVISORSIndustry Veterans, Renowned Oncologists and Immunologists
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Miriam Merad, MD, PhD
Multi-year strategic collaboration
Steven HoltzmanPresident and CEO, Decibel TherapeuticsFormer CBO and CEO
Antoni Ribas, MD, PhDDrew Pardoll, MD, PhDChairman of the SAB
Multi-year strategic collaboration
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FROM CODE TO CURE
Thank you
www.cgen.com
January 2019
Anat Cohen-Dayag, PhD
President & CEO
TM