Innate Pharma Sa Class A · EURONEXT:IPH
Innate Pharma Sa Class A — Investor Day (March 2018)
146 slides from Innate Pharma Sa Class A's investor day presentation, Mar 8, 2018
Slide 1: The Innate Immunity Company – R&D Day 2018
THE INNATE IMMUNITY COMPANY R&D DAY 2018 LONDON, MARCH 8
Slide 2: Forward Looking Statement
FORWARD LOOKING STATEMENT This document has been prepared by Innate Pharma S.A. (the The information contained herein has not been independently “Company”) solely for the purposes of a presentation to verified. No representation, warranty or undertaking, express or investors concerning the Company.
Slide 3: Today's Speakers
TODAY’S SPEAKERS Mondher Eric Pierre Julia Mohammed MAHJOUBI, MD, VIVIER, DVM, PhD DODION, MD, MBA, SCARISBRICK, MD, DAR, MD, Chief Executive Officer Chief Scientific Officer Chief Medical Officer Dermatologist & Lead, VP Clinical Development Innate Pharma Innate Pharma Innate Pharma Cutaneous Lymph
Slide 4: Agenda
AGENDA 1 STRATEGY INTRODUCTION – MONDHER MAHJOUBI 2 BUILDING AN INNOVATIVE AND DIFFERENTIATED PIPELINE – ERIC VIVIER 3 PROPRIETARY PIPELINE – PIERRE DODION > IPH5401 – POTENTIAL TO UNLOCK THE IMMUNE RESPONSE > IPH4102 – NEW THERAPEUTIC OPTION FOR T-CELL LYMPHOMA – JULIA SCARISBRICK 4 PARTNERED PIPEL
Slide 5: Strategy Introduction
STRATEGY INTRODUCTION MONDHER MAHJOUBI CHIEF EXECUTIVE OFFICER
Slide 6: Key Messages
KEY MESSAGES World-class science and technology platform Clinical read-outs ahead for monalizumab and IPH4102 programs Delivering on IPH5401 with clinical collaborations to accelerate development Potential to address large unmet medical needs in cancer Financial strength, enabling room for investmen
Slide 7: Innate Pharma – Strategy
INNATE PHARMA – STRATEGY SCIENCE DRIVEN ORGANIZATION AND PATIENT CENTRIC COMPANY Create diverse portfolio of first or best-in-class IO agents Strategic Partner with leading IO companies to unlock the value of assets Priorities with substantial market potential Retain more value in house and move tow
Slide 8: Innate Pharma – Approach
INNATE PHARMA – APPROACH SCIENTIFIC EXCELLENCE AROUND 3 KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) 8
Slide 9: Innate Pharma – Pipeline
INNATE PHARMA – PIPELINE FIRST-IN-CLASS IMMUNO-ONCOLOGY (IO) ASSETS Target Drug Signal Preclinical Dose finding Pivotal Discovery Discovery detection IPH52 IPH5401 Monalizumab Anti-Siglec-9 ~20 targets or Anti-CD39 Anti-C5aR Anti-NKG2A concepts under exploration IPH53 Lirilumab SAN-NKCE-2 Anti-CD73
Slide 10: Priorities and Key Catalysts
INNATE PHARMA – PRIORITIES AND KEY CATALYSTS • Read-out of current clinical programs > Monalizumab w/ cetuximab in advanced SCCHN @AACR > Monalizumab w/ durvalumab in solid tumors > Cohort expansion data for IPH4102 Key Value • Preparing next stages of clinical studies Creation > IPH4102: lifting th
Slide 11: FY2017 Results
FY2017 RESULTS FINANCIAL STRENGTH, ENABLING INVESTMENTS IN FUTURE GROWTH Revenue*: €44m • Mainly from industrial partnerships • Increase in R&D expenses support clinical Op. expenses: €84m development of IPH4102 and monalizumab • 2017 cash burn €54m** Cash position: €177m • Strong cash position to i
Slide 12: Building an Innovative and Differentiated Pipeline
BUILDING AN INNOVATIVE AND DIFFERENTIATED PIPELINE ERIC VIVIER CHIEF SCIENTIFIC OFFICER
Slide 13: Experience
EXPERIENCE 30 YEARS IN ACADEMIC RESEARCH - IMMUNOLOGY • D.V.M, PhD (Paris XI) • Harvard Medical School • Centre d’Immunologie de Marseille-Luminy • Scripps, Rockefeller, WEHI • European Research Council Laureate – Highly cited researcher
Slide 14: Why Innate Pharma?
EXPERIENCE 30 YEARS IN ACADEMIC RESEARCH - IMMUNOLOGY WHY INNATE MISSION MEANS PHARMA? • Translating science • Expertise • World-class biotech into survival • Technology company • Finding new targets, • Academic & industrial • 4 first-in-class new formats network molecules in 15 years • Identifying
Slide 15: Cancer: A Global Challenge
CANCER: A GLOBAL CHALLENGE AACR Cancer Progress Report, 2017
Slide 16: The Immune System
THE IMMUNE SYSTEM CHALLENGES • Microbial infections • Tumors NK Innate lymphoid Dendritic cells Neutrophils Monocytes Mastocytes cells Eosinophils Macrophages Groups 1, 2, 3 Basophils INNATE IMMUNITY EFFECTOR RESPONSE • Hours • Whole body Naïve B&T • Days cells • From lymphoid organs ADAPTATIVE IMMU
Slide 17: A Brief History of Anti-Tumor Immunosurveillance
A BRIEF HISTORY OF ANTI-TUMOR IMMUNOSURVEILLANCE 2001 1891 Saint Louis, USA New York City, USA 1967 1980 Robert D. Schreiber William Coley Villejuif, France Bruxelles, Belgique Tumor editing ‘Coley toxine’ Georges Mathé Thierry Boon BCG Tumor antigens 1975 1996 2002 1957 Bethesda, USA, Berkeley, USA
Slide 18: The Immuno-Oncology Revolution
THE IMMUNO-ONCOLOGY REVOLUTION DIRECT TARGETING OF TUMOR CELLS: INDIRECT TARGETING OF TUMOR CELLS: i.e. via tumor antigens i.e. via immune checkpoints Tumor Immune Tumor cell effector cell • Surgery + • Radiotherapy _ • Chemotherapy Immune Checkpoint Inhibitors 18
Slide 19: The mAb Revolution in Cancer Immunotherapy
THE MAB REVOLUTION IN CANCER IMMUNOTHERAPY Resistant to chemo Anti-PD1 mAbs Baseline 12 weeks 24 weeks 52 weeks C. Robert, IGR 19
Slide 20: What's Next in Immuno-Oncology?
WHAT’S NEXT IN IMMUNO-ONCOLOGY? Immune Checkpoint Inhibitors • anti-CTLA-4 > Ipilimumab (YERVOY, BMS) Proportion alive > Tremelimumab (MEDIMMUNE-ASTRAZENECA) ? • anti-PD-1 Immunotherapy (combination) > Nivolumab (OPDIVO, BMS/ONO) LT survival > Pembrolizumab (KEYTRUDA, MERCK) Immunotherapy (monothera
Slide 21: What's Next in Immuno-Oncology?
WHAT’S NEXT IN IMMUNO-ONCOLOGY? • Understand the resistance to Immune Checkpoint Inhibitors • Increase the fraction of patients sensitive to IO treatments • Decrease toxicity • Identify new targets (cells and molecules) • Identify biomarkers 21
Slide 22: What's Next in Immuno-Oncology?
WHAT’S NEXT IN IMMUNO-ONCOLOGY? • Understand the resistance to Immune Checkpoint Inhibitors • Increase the fraction of patients sensitive to IO treatments • Decrease toxicity • Identify new targets (cells and molecules) • Identify biomarkers 22
Slide 23: Natural-killer cells sound the alarm against cancer
Natural-killer cells sound the alarm against cancer nature.com innate phe
Slide 24: Broad and Differentiated Portfolio of IO Assets
BROAD AND DIFFERENTIATED PORTFOLIO OF IO ASSETS Target Drug Signal Preclinical Dose finding Pivotal Discovery Discovery detection IPH52 IPH5401 Monalizumab Anti-Siglec-9 ~20 targets or Anti-CD39 Anti-C5aR Anti-NKG2A concepts under exploration IPH53 Lirilumab SAN-NKCE-2 Anti-CD73 Anti-KIR2DL1,2,3 Oth
Slide 25: Building an Innovative and Differentiated Pipeline
BUILDING AN INNOVATIVE AND DIFFERENTIATED PIPELINE Human surfaceome 20,000+ genes 35,000+ proteins 7,000+ proteins that can be expressed at the cell surface Largely unexplored Expression: Single cell genome-wide analysis Inhibitory Inhibitory receptor ligand - Function: Cell-based assays + Tumor Ag
Slide 26: Next Generation IO
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS TO HARNESS THE POTENTIAL OF IMMUNITY 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) 26
Slide 27: Next Generation IO – Our Strategy
NEXT GENERATION IO OUR STRATEGY UNIQUE FIRST-IN-CLASS DIVERSIFIED POSITIONNING BEST-IN-CLASS APPROACH 27
Slide 28: Pipeline: Targeting Different Status of the Immune Response
INNATE PHARMA – PIPELINE TARGETING DIFFERENT STATUS OF THE IMMUNE RESPONSE No effective Anti-tumor immunity Sub-optimal or exhausted anti-tumor immunity suppressed by TME anti-tumor immunity Noninflamed Inflamed NK Bispecific IPH5401 Lirilumab Engagers Anti-C5aR Anti-KIR2DL1,2,3 Antibody Drug IPH53
Slide 29: Next Generation IO – NK Cell Checkpoints
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) NKG2A NK cell checkpoints 29
Slide 30: Anti-NKG2A Is a Novel Immune Checkpoint Inhibitor in Cancer
ANTI-NKG2A IS A NOVEL IMMUNE CHECKPOINT INHIBITOR IN CANCER • Monalizumab (IPH2201) is a first-in-class anti-NKG2A humanized blocking antibody Anti-NKG2A _ NKG2A HLA-E - + Activating Activating + receptor ligand HLA-E MHC NKG2A _ TCR + + NK cell and T cell inhibition by NKG2A + Activation by NKG2A b
Slide 31: NKG2A/HLA-E Pathway Is Upregulated in Tumors
NKG2A / HLA-E PATHWAY IS UPREGULATED IN TUMORS HLA-E on tumor cells NKG2A on TILs 100 P e r c e n ta g e o f p a tie n ts 75 50 25 0 0) 0) 0) 0) 6) *) 7) 7) =2 =4 =4 =4 =1 ) ( =4 =4 (n (n ) (n ) (n (n = 1 5 ) (n ) (n l ) l N ry or a ma a l (n a ma H& va or a) or O m s tro m s tro a tu ( t u mro m a
Slide 32: NKG2A/Qa-1b Control Tumor Growth
NKG2A/QA-1b CONTROL TUMOR GROWTH b A 20 A 2 0 Q a -1 K O 2000 2000 TF: 0% TF: 20% ) ) 3 C R :0 % 3 C R :5 0 % T u m o r v o lu m e (m m T u m o r v o lu m e (m m 1500 1500 1000 1000 500 500 0 0 0 5 10 15 20 25 30 0 5 10 15 20 25 30 D ays D ays Individual A20 and A20 Qa-1b KO and A20 PD-L1 KO tumor g
Slide 33: PD-1high CD8+ TILs Co-express NKG2A
PD-1HIGH CD8+ TILS CO-EXPRESS NKG2A CD8+ TILs PD-1 NKG2A Expression of NKG2A and PD-1 on isolated CD8+ TILs (day 20) A20 B cell lymphoma into BALB/C mice André et al. unpublished NK cell checkpoints 33
Slide 34: NKG2A and PD-L1 Blockades Are Complementary
NKG2A AND PD-L1 BLOCKADES ARE COMPLEMENTARY Anti-NKG2A _ NKG2A HLA-E - + Activating Activating + receptor ligand HLA-E MHC PD-L1 NKG2A _ TCR Anti-PD-L1 + _ PD-1 + or PD-1 NK cell and T cell inhibition by NKG2A + Activation by NKG2A blockade NK cell checkpoints 34
Slide 35: NKG2A Blockade Increases PD-L1 Anti-Tumoral Efficacy
NKG2A BLOCKADE INCREASES PD-L1 ANTI-TUMORAL EFFICACY s u r v iv a l 100 c o n tro l P e r c e n t s u r v iv a l 80 a n ti-m N K G 2 A a n ti- m P D - L 1 *** 60 * a n ti-m N K G 2 A + a n ti-P D -L 1 40 20 0 0 10 20 30 days RMA-Rae1 into B6 mice P=0.03 (*), P=0.0006 (***), Grehan-Breslow-Wilcoxon t
Slide 36: NKG2A Blockade Enhances ADCC in a HLA-E+ Context
NKG2A BLOCKADE ENHANCES ADCC IN A HLA-E+ CONTEXT Anti-NKG2A _ NKG2A HLA-E - Tumoral + CD16 Activating Ag + receptor NK cell inhibition by NKG2A + ADCC enhancement by NKG2A blockade NK cell checkpoints 36
Slide 37: NKG2A Blockade Enhances Cetuximab-Induced ADCC of H&N Tumor Cells
NKG2A BLOCKADE ENHANCES CETUXIMAB-INDUCED ADCC OF H&N TUMOR CELLS NK cell checkpoints 37
Slide 38: Next Generation IO – Tumor Targeting
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) KIR3DL2 MICA/B NKp46 NKCE Tumor targeting 38
Slide 39: Next Generation IO – Tumor Targeting
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) KIR3DL2 MICA/B NKp46 NKCE Tumor targeting 39
Slide 40: KIR3DL2 Is a Tumor Specific Antigen in CTCL
KIR3DL2 IS A TUMOR SPECIFIC ANTIGEN IN CTCL • IPH4102 is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody Tumor targeting 40
Slide 41: KIR3DL2 Targeting Induces Anti-Tumoral Efficacy
KIR3DL2 TARGETING INDUCES ANTI-TUMORAL EFFICACY Control Anti-KIR3DL2 Marie-Cardine et al, Cancer Res 2014 Tumor targeting 41
Slide 42: Next Generation IO – Tumor Targeting
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) KIR3DL2 MICA/B NKp46 NKCE Tumor targeting 42
Slide 43: MICA/B Is Induced on Tumor Cells and Downregulates NKG2D
MICA/B IS INDUCED ON TUMOR CELLS AND DOWNREGULATES NKG2D + Tumor targeting 43
Slide 44: MICA/B Can Be Targeted by Naked Ab or ADC
MICA/B CAN BE TARGETED BY NAKED AB OR ADC Anti-MICA naked Ab Anti-MICA-ADC TRAMP-MICB tumor model PDX (human breast) P D X (h u m a n b re a s t) 1500 C o n tro l-A D C T u m o r v o lu m e ( m m ) 3 a n ti M IC A -A D C 1000 B e v a c iz u m a b M ean SEM 500 10/10 CR 0 0 10 20 30 40 50 60 70 80
Slide 45: Next Generation IO – Tumor Targeting
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) KIR3DL2 MICA/B NKp46 NKCE Tumor targeting 45
Slide 46: NK Cell Engager (NKCE) Multispecific Antibody Technology
NK CELL ENGAGER (NKCE) MULTISPECIFIC ANTIBODY TECHNOLOGY • NKp46-NKCE binds to > an antigen at the surface of tumor cells > NKp46 activating receptor on NK cells and CD16 (FcgRIII) CD16 NKCE • NKp46-NKCE may reduce the risk of TAg side-effects associated with T cell engagers • Library of proprietary
Slide 47: Anti-CD20-NKp46-NKCE Induces Anti-Tumoral Efficacy
ANTI-CD20-NKP46-NKCE INDUCES ANTI-TUMORAL EFFICACY In vitro In vivo 1 0 0 8 0 c o n tro l P e r c e n t s u r v iv a l A n t i- C D 2 0 - N K C E 8 0 % s p e c ific ly s is 6 0 IC -N K C E O b in u tu z u m a b 6 0 A n t i- C D 2 0 - N K C E 4 0 IC -Ig G 1 + 4 0 IC -N K C E O b in u tu z u m a b 2 0
Slide 48: Next Generation IO – Tumor Microenvironment
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) Adenosine pathway MDSC Tumor microenvironment 48
Slide 49: Next Generation IO – Tumor Microenvironment
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) Adenosine pathway MDSC Tumor microenvironment 49
Slide 50: Adenosine Pathway Is Immunosuppressive in the TME
ADENOSINE PATHWAY IS IMMUNOSUPPRESSIVE IN THE TME B cells, naïve Treg, B and CD8+ T cells myeloid cells Anti-CD73 Tumor spreading CD39 CD73 sCD73 NK cells AMP Adenosine AMP sCD39 ATP ATP A2A/2B receptors Immunosuppression CD8+ or P2X receptors CD4+ T cells Dendritic cell ATP : adenosine triphosphate
Slide 51: CD39 Expression in Head and Neck Tumors
CD39 EXPRESSION IN HEAD AND NECK TUMORS CD39 CD39 is expressed on TILs and vascular endothelial cells Tumor microenvironment 51
Slide 52: CD39 Blockade Inhibits ATP Degradation and Adenosine Generation
CD39 BLOCKADE INHIBITS BOTH ATP DEGRADATION AND ADENOSINE GENERATION B cells, naïve Treg, B and CD8+ T cells myeloid cells Tumor spreading Anti-CD73 CD39 CD73 sCD73 Anti-CD39 NK cells Anti-CD39 AMP Adenosine AMP sCD39 ATP ATP A2A/2B receptors Immunosuppression CD8+ or P2X receptors CD4+ T cells Dend
Slide 53: Lead Anti-CD39 Ab Restores Immune Response in Presence of ATP
LEAD ANTI-CD39 AB RESTORES IMMUNE RESPONSE IN THE PRESENCE OF ATP T cell proliferation assay DC activation C D 8 3 p o s itiv e c e lls (% ) C D 4 T c e lls C D 8 T c e lls P r o life ra tin g T C e lls (% ) P r o life ra tin g T C e lls (% ) 60 100 100 A ct 80 80 40 60 60 A ct + A TP 40 40 20 20 20
Slide 54: CD39 and CD73 Expression in Head and Neck Tumors
CD39 AND CD73 EXPRESSION IN HEAD AND NECK TUMORS CD39 CD73 CD39 is expressed on TILs and vascular CD73 is expressed on tumor cells, TILs and endothelial cells vascular endothelial cells Tumor microenvironment 54
Slide 55: CD39/CD73 Blockade Synergize to Reverse ATP-Mediated T Cell Suppression
CD39/CD73 BLOCKADE SYNERGIZE TO REVERSE ATP-MEDIATED T CELL SUPPRESSION CD4+ T cells CD39+CD73 54.6% CD39 35.3% CD73 28.3% ATP 22.6% 52.2% CD3 + CD28 6.6% Control 0 20 40 60 P rProliferating o l i f e r a t i n gT Tcells c e l(%) ls (% ) Proliferating T cells (%) Tumor microenvironment 55
Slide 56: CD39/CD73 Blockade Aims at Reversing Immunosuppression in the TME
CD39/CD73 BLOCKADE AIMS AT REVERSING IMMUNOSUPPRESSION IN THE TME B cells, naïve Treg, B and CD8+ T cells myeloid cells Anti-CD73 Anti-CD73 Tumor depletion CD39 CD73 sCD73 Anti-CD39 NK cells Anti-CD39 AMP sCD39 ATP ATP Activation CD8+ or P2X receptors CD4+ T cells Dendritic cell ATP : adenosine trip
Slide 57: Next Generation IO – Tumor Microenvironment
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) Adenosine pathway MDSC Tumor microenvironment 57
Slide 58: C5aR Blockade Inhibits MDSC/Neutrophil Recruitment and Activation
C5AR BLOCKADE INHIBITS MDSC/NEUTROPHIL RECRUITMENT AND ACTIVATION IN THE TME Anti-PD-1 + Tumor microenvironment 58
Slide 59: C5aR/PD-1 Blockade Induces Tumor Growth Inhibition in PD-1 Resistant Model
C5AR/PD-1 BLOCKADE INDUCES TUMOR GROWTH INHIBITION IN A PD-1 RESISTANT MODEL T u m o r G r o w th In h ib itio n (% ) 80 60 T G I (% ) 40 20 0 0 0 0 0 0 0 0 0 5 0 5 0 1 1 2 3 T u m o r v o lu m e (m m ) A n t i- P D - 1 A n t i- C 5 a R + r I g G 2 a A n ti- C 5 a R + A n ti- P D - 1 Fares et al. IC
Slide 60: Broad and Differentiated Portfolio of IO Assets
BROAD AND DIFFERENTIATED PORTFOLIO OF IO ASSETS Target Drug Signal Preclinical Dose finding Pivotal Discovery Discovery detection IPH52 IPH5401 Monalizumab Anti-Siglec-9 ~20 targets or Anti-CD39 Anti-C5aR Anti-NKG2A concepts under exploration IPH53 Lirilumab SAN-NKCE-2 Anti-CD73 Anti-KIR2DL1,2,3 Oth
Slide 61: Think, Be Creative, Provide Solutions – Opening
THINK BE CREATIVE PROVIDE SOLUTIONS OPENING 62
Slide 62: Proprietary Portfolio
PROPRIETARY PORTFOLIO PIERRE DODION CHIEF MEDICAL OFFICER
Slide 63: Next Generation IO – IPH5401 (C5aR)
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) IPH5401 (target: C5aR) 64
Slide 64: What Is IPH5401?
WHAT IS IPH5401? • C5aR inhibitor: monoclonal antibody targeting the receptor (C5aR) to C5a • C5a results from the cleavage of C5 as part of the complement cascade • C5a stimulates the recruitment and functional activation of myeloid derived suppressor cells (MDSCs) and regulatory T-cells (Tregs) >
Slide 65: Mechanism of Action IPH5401
MECHANISM OF ACTION IPH5401 ADDING A C5AR INHIBITOR RESTORES THE EFFICACY OF PD1/PDL1 BLOCKERS C5a C5a MHC MHC TCR TCR Anti-PD-1 Anti-PD-1 or PD-L1 or PD-L1 Ìnhibition of IPH5401 migration & function C5aR receptor C5aR receptor MDSC/ + Neutrophils MDSC/ Combined treatment Neutrophils PD1/PDL1 blocke
Slide 66: IPH5401: Phase 1 Safety, PK and PD Data
IPH5401: PHASE 1 SAFETY, PHARMACOKINETIC AND PHARMACODYNAMIC DATA Favorable safety profile in single & multi-dose, placebo controlled phase 1 trials in RA1 Single dose Multiple dose Dose range (mg/kg) 0.02-10 (iv) 0.2-4 (sc) 0.25-4 (sc) Nr of pts (IPH5401/placebo) 27 / 9 18 / 6 % pts with AE (IPH540
Slide 67: Prioritized Indications Based on C5aR Expression
PRIORITIZED INDICATIONS BASED ON C5AR EXPRESSION1 C5aR Tumor type 1 Impact on prognosis expression NSCLC 80% Poor prognosis UCC 73% Poor prognosis HCC 68% Not known CRC 60% Not known RCC 61% Not known Gastric cancer 30-35% Poor prognosis Prostate cancer 35% Poor prognosis Breast cancer 13% Poor prog
Slide 68: C5aR Expression Negatively Impacts Long Term Outcome in NSCLC
C5AR EXPRESSION NEGATIVELY IMPACTS LONG TERM OUTCOME IN NSCLC C5aR expression impact on long term outcome in 208 previously An increase in C5aR untreated NSCLC expression by neutrophils is seen in NSCLC • The 5-year OS was significantly lower in high expressors of C5aR than in low expressors (p = 0.
Slide 69: Prioritized Indications Based on Medical Need
PRIORITIZED INDICATIONS BASED ON MEDICAL NEED AND POTENTIALLY ACCELERATED PATH TO MARKET Tumor type Description of unmet medical need NSCLC • second line, post platinum: rate of long term failure as high as 80%: • first line: rate of long term failure of 30% HCC 272 pts with squamous histology, 2nd
Slide 70: Prioritized Indications Based on Medical Need
PRIORITIZED INDICATIONS BASED ON MEDICAL NEED AND POTENTIALLY ACCELERATED PATH TO MARKET Tumor type Description of unmet medical need NSCLC • second line, post platinum: rate of long term failure as high as 80%: • first line: rate of long term failure of 30% HCC • second line post sorafenib • Sorafe
Slide 71: AstraZeneca Collaboration to Accelerate Proof-of-Concept
ASTRAZENECA COLLABORATION TO ACCELERATE PROOF-OF-CONCEPT IN NSCLC AND HCC AstraZeneca/MedImmune Collaboration Type of collaboration Clinical agreement (access to drug, 50% trial cost sharing) Tumor type for expansion NSCLC 2ary resistance (IO pretreated) cohorts IO naive HCC = unmet medical needs PD
Slide 72: Smart Development Program with Limited Dose-Escalating Part
SMART DEVELOPMENT PROGRAM WITH LIMITED DOSE-ESCALATING PART • In combination with durvalumab • Very limited dose escalation part • Cohort expansion(s) at recommended phase 2 dose/schedule • Indications selection: NSCLC, HCC • Extensive PK/PD exploration (e.g. C5aR, C5a, MDSCs, CD8, PDL1, cytokines,
Slide 73: Combination IPH5401 + Durvalumab Proposed Study Design
COMBINATION IPH5401 + DURVALUMAB PROPOSED STUDY DESIGN Dose escalation part: 3+3 model Cohort expansion part: primary endpoint: safety, RP2D primary endpoint: ORR (Simon 2-stage) design IPH5401 DL3, schedule 2 + durvalumab NSCLC (secondary resistance to Stage 2 IPH5401 DL3, PD1/PDL1 blockers) schedu
Slide 74: Phase 1 to Start 2H2018
PHASE 1 TO START 2H2018 Phase 2, other Pivotal program IPH5401 in other indications indications Accelerated pivotal program IPH5401 in NSCLC and/or HCC Dose Expansion escalation cohort Pivotal program IPH5401 in NSCLC NSCLC and NSCLC and/or HCC and HCC HCC 2019 2020 2021 2022 2023 2024 2025 All elem
Slide 75: Abundant Life Cycle Opportunities
ABUNDANT LIFE CYCLE OPPORTUNITIES A COHERENT VISION OF MULTIPLE INDICATIONS, LINES OF THERAPIES AND DEGREE OF RESISTANCE Tumor type Setting NSCLC Secondary resistance to PD1/PDL1 blockers, in combination with durvalumab HCC PD1 naïve, in combination with durvalumab IO untreated patients in combinati
Slide 76: Summary
SUMMARY Inhibition of C5aR signaling increases effector cell infiltration and function in the TME 1 Long-term failure rates of PD-1/L1 therapy create demand for combination strategies Prioritization of indications based on C5aR expression and medical need 2 Clinical collaborations enhance program va
Slide 77: Next Generation IO – IPH4102 (KIR3DL2)
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) IPH4102 (target: KIR3DL2) IPH4102 78
Slide 78: KIR3DL2 Is Widely Expressed on T Cell Lymphomas
KIR3DL2 IS WIDELY EXPRESSED ON T CELL LYMPHOMAS • KIR3DL2 is specifically expressed on cutaneous and circulating cutaneous T-cell lymphomas (CTCL) cells (various grades and subtypes): SS pt, grade IIIB > Expressed by ~65% of all CTCL patients 87% KIR3DL2+ tumor cells1 > Expressed by up to 85% of CTC
Slide 79: IPH4102: Mode of Action
IPH4102: MODE OF ACTION PROMISING ACTIVITY IN SÉZARY SYNDROME • IPH4102 : first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody • Designed to selectively destroy KIR3DL2-expressing CTCL cancer cells: > upon binding to the receptor, the Fc domain of IPH4102 activates antibody dependent
Slide 80: What Is CTCL?
WHAT IS CTCL? • Non Hodgkin’s lymphoma, originating from T cells and with a tropism for the skin • 4% of Non Hodgkin’s Lymphoma > ~ 1 / 100,000 (6,000 new cases for the US + EU) > Rising annual incidence in US - ↑ by 2.9 per million per decade • Clinically: > Median age at diagnosis of 55-65 years >
Slide 81: Epidemiology of CTCL (1)
EPIDEMIOLOGY OF CTCL (1) Nr new 5-yr overall cases/yr survival 6,000 3,300-3,900 20-95% 150-300 < 15% 500-1000 76-96% 150-300 ~ 10% 600 < 20% LPD: lymphoproliferative disorder. ALCL: anaplastic large cell lymphoma ATL: Adult T cell lymphoma Agar et al, JCO 2010; Kempf et al, Blood 2011; Willemze, Bl
Slide 82: Epidemiology of CTCL (2)
EPIDEMIOLOGY OF CTCL (2) • Besides the histological subtypes, prognosis and survival of CTCL are strongly linked to clinical stage • Other poor prognostic factors: age >60 years, large cell transformation (LCT) in skin, increased Lactate Dehydrogenase (LDH) and extracutaneous involvement Agar et al,
Slide 83: Treatment of CTCL
TREATMENT OF CTCL OVERVIEW Initial diagnosis Early stage disease Advanced stage disease ~ 65% of the patients ~ 35% of the patients Skin directed therapy Systemic therapy Disease control Progression ~ 75% ~ 25% IPH4102 84
Slide 84: Standards of Care in CTCL
STANDARDS OF CARE IN CTCL LIMITED TO MYCOSIS FUNGOIDES (AFTER FAILURE OF LOCAL THERAPIES)1 Preferred therapies 1st line Bexarotene, bexarotene-based combinations 2nd line Interferon, methotrexate, gemcitabine, liposomal-doxorubicin 3rd line Methotrexate, CHOP, palatrexate 4th line Romidepsin Lines a
Slide 85: Treatment of CTCL: New Agents – Brentuximab
TREATMENT OF CTCL NEW AGENTS WITH ACTIVITY: BRENTUXIMAB • Brentuximab vedotin (Anti CD30 ADC): > CTCL (CD30 positive; excl. SS): phase 3 study (ALCANZA) against investigator’s choice (methotrexate/bexarotene) (128 pts) > ORR4: 61 vs 8% (p < 0.001); med PFS: 15.8 vs 3.6 months (HR=0.37, p < 0.001) >
Slide 86: Mogamulizumab, a CCR4 Inhibitor, in CTCL
MOGAMULIZUMAB, A CCR4 INHIBITOR, IN CTCL NEW AGENTS WITH ACTIVITY: MOGAMULIZUMAB 372 pts with MF or SS, in failure post ≥ 1 systemic therapy, randomized between mogamulizumab and vorinostat Group 1 PFS (mos) 1,2 ORR Toxicity Mogamulizumab 7.7 28% Infusion related reaction, cutaneous toxicity Vorin
Slide 87: Standards of Care in CTCL – Future
STANDARDS OF CARE IN CTCL HOW WILL MYCOSIS FUNGOIDES BE TREATED IN THE FUTURE? KOLs opinion: Bexarotene likely to stay the primary agent in 1st line (oral) Strong impact of brentuximab & mogamulizumab in later lines Predicted preferred therapies 1st line Bexarotene, bexarotene-based combinations 2nd
Slide 88: CTCL: Foundations of Our Clinical Development Plan
CTCL FOUNDATIONS OF OUR CLINICAL DEVELOPMENT PLAN • Single agent approach after 2 lines of prior systemic therapy, including biologics • Multiple different subtypes with a variable prognosis • Variable stages (IB-IV) Supports a randomized • Complex treatment algorithms program > Variable local thera
Slide 89: CTCL: Clinical Development Program
CTCL CLINICAL DEVELOPMENT PROGRAM1 • Population: advanced after 2 lines of prior systemic therapies, including brentuximab / mogamulizumab > Leveraging IPH4102 in patients with unmet medical need • Randomized program of single agent IPH4102 • Comparator: investigator choice (gemcitabine, vorinostat)
Slide 90: Sézary Syndrome
SÉZARY SYNDROME CLINICAL FEATURES AND SIMPLIFIED TREATMENT APPROACH • Leukemic variant of CTCL – stage IV in all cases – poor prognosis • Systemic therapy is the standard of care • Older drugs/approaches > First line setting: extracorporeal phototherapy, bexarotene, interferon (combinations > sing
Slide 91: Sézary Syndrome: Overall Treatment Approach in 2018
SÉZARY SYNDROME OVERALL TREATMENT APPROACH IN 2018 • ECP, bexarotene, Interferon , Methotrexate, or combination of these approaches st likely to stay the main approach in “1 line” • Mogamulizumab likely to be approved (PDUFA date: June 4, 2018) and to penetrate nd the “2 line” setting rd • 3 + line
Slide 92: Pivotal Program in Sézary Syndrome
PIVOTAL PROGRAM IN SÉZARY SYNDROME STUDY DESIGN – POTENTIAL ACCELERATED APPROVAL SS Regulatory consultations IPH4102 IV Primary endpoint: After 2 systemic 1. Preclinical data therapies including (750 mg) ORR4 biological agents 2. “Isolation” of SS 3. ORR4 as 1ary endpoint, PFS as key 2ary endpoint 4
Slide 93: Potential Development Paths in Other Lymphomas – PTCL
POTENTIAL DEVELOPMENT PATHS IN OTHER LYMPHOMAS PTCL • PTCL represent ~10% of all NHL WW • Several subtypes with variable response to therapy and outcome • ~ 50% express KIR3DL2 Standard of care PTCL Incl. ALCL 1st line Chemo (CHOP-like) at times followed by transplantation if possible 2nd line*, Gem
Slide 94: Potential Development Paths in Other Lymphomas – ATLL
POTENTIAL DEVELOPMENT PATHS IN OTHER LYMPHOMAS ATLL • ATLL prevalence follows the distribution of the oncogenic HTLV-1 virus > <10% of all PTCL WW (~25% in Japan) > Annual incidence: WW: ~1,400; Japan: ~700-1,000 • Several subtypes with variable response to therapy and outcome • KIR3DL2 expressed in
Slide 95: Clinical Development Plans in PTCL and ATLL
CLINICAL DEVELOPMENT PLANS IN PTCL AND ATLL1 • High interest of the medical community • PTCL • ATLL > Preliminary IHC data showing positive > High prevalence of KIR3DL2 expression KIR3DL2 in about 50% of the pts (>80%) in the acute form (most frequent > Preliminary preclinical data supporting a and
Slide 96: Clinical Development Plan Across Patient Populations
CLINICAL DEVELOPMENT PLAN1 ACROSS PATIENT POPULATIONS SUMMARY Pivotal program IPH4102 in PTCL Pivotal program IPH4102 in ATLL Pivotal program IPH4102 in CTCL Pivotal program IPH4102 in SS 2019 2020 2021 2022 2023 2024 2025 Potential Biologics License Application. 1. All elements of study design and
Slide 97: Targeting KIR3DL2 in CTCL – Phase 1 Dose Escalation
TARGETING KIR3DL2 IN CTCL PHASE 1 DOSE ESCALATION Dr. Julia Scarisbrick MBChB, FRCP, MD University Hospitals Birmingham NHS Foundation Trust St Thomas Hospitals The London Skin Clinic IPH4102 98
Slide 98: Signs and Symptoms of Mycosis Fungoides and Sézary Syndrome
SIGNS AND SYMPTOMS OF MYCOSIS FUNGOIDES (MF) AND SÉZARY SYNDROME (SS) Early Stages Advanced Stages • General > Itching > Disfigurement > Pain > Sleep disturbance > Psycho-social disorders > High disease burden plaques tumors erythroderma > Quality of life impairment IPH4102 99
Slide 99: Therapies in Early-Stage CTCL
THERAPIES IN EARLY-STAGE CTCL (PATCH/PLAQUE) • Skin directed therapy > No treatment shown to be superior > Typically associated with short response duration > 50-60% of patients will have recurrent disease > Few durable complete responses > Life expectancy may be normal > Morbidity may be significan
Slide 100: Therapies in Advanced-Stage CTCL
THERAPIES IN ADVANCED-STAGE CTCL • Chemotherapy (1970’s) • Immunotherapy (interferon 1980’s) • Extracorporeal photopheresis (1987) • Novel retinoids (bexarotene 1999) • Monoclonal antibody therapy (1997/2001/2017) • Autologous / Allogeneic stem cell transplants (2000) • Histone deacetylase inhibitor
Slide 101: Real-World Treatment
REAL-WORLD TREATMENT Heterogeneity of treatment approaches were found, with up to 24 different modalities or combinations used as first-line and 31% of patients receiving 4 or more treatments 100% 80% 60% 40% 20% 0% 1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th ECP * Bexarotene Phototherapy * MTX INF * L
Slide 102: Unmet Needs in CTCL
UNMET NEEDS IN CTCL • Effective treatments > Most have RR in 20-40% > Most have short response duration 6-9 months > Best combinations • Effective symptom relief > Patients have severe itch > Sleep disturbance IPH4102 103
Slide 103: Summary Treatment Guidelines
SUMMARY TREATMENT GUIDELINES • Early-stage CTCL should be treated with skin directed therapies • Advanced-stage CTCL require systemic therapy > No algorithm for treatment which is typically patient specific > No regime proven to improve survival > Most patients receive multiple consecutive therapies
Slide 104: KIR3DL2 Is a Therapeutic Target in CTCL
KIR3DL2 IS A THERAPEUTIC TARGET IN CTCL • KIR3DL2 belongs to the Killer Ig-like Receptor family that modulate NK and T cell activity • KIR3DL2 is expressed on <10% normal T cells • KIR3DL2 is widely expressed on CTCL cells (skin lesions and blood aberrant cells) > Irrespective of disease clinical st
Slide 105: KIR3DL2 Is Expressed on Most CTCL Subtypes
KIR3DL2 IS EXPRESSED ON MOST CTCL SUBTYPES Positivity threshold = 5% 80-100% cases are KIR3DL2+ EID: erythrodermic inflammatory disease; MF: Mycosis Fungoides; SS: Sézary Syndrome; cALCL: primary cutaneous Anaplastic Large Cell Lymphoma; LyP: Lymphomatoid papulosis; HTLV1: (primary cutaneous) Human
Slide 106: IPH4102-101 First-in-Human Phase 1 Study Design and Objectives
IPH4102-101 FIRST-IN-HUMAN PHASE 1 STUDY DESIGN AND OBJECTIVES Cohort expansion in Dose-escalation subtypes of CTCL (doses in mg/kg) RP2D for cohorts • Dose-escalation (10 dose levels – accelerated 3+3 design) followed by cohort expansion • Primary objective: determination of Maximal Tolerated Dose
Slide 107: Baseline Disease Characteristics (Dose-Escalation)
BASELINE DISEASE CHARACTERISTICS (DOSE-ESCALATION) All doses N = 25 Age (years), median (min; max) 71 (42; 90) MF/SS CTCL type, n (%) Mycosis fungoides (MF) 4 (16) Sézary Syndrome (SS) 20 (80) Non MF/SS CTCL type, n (%) CD4+ T-cell lymphoma, NOS 1 (4) Clinical stage at study entry (MF/SS), n (%) IB
Slide 108: Summary of Adverse Events (Dose-Escalation)
SUMMARY OF ADVERSE EVENTS (AE) (DOSE-ESCALATION) N = 25 Total Grade 3 Grade 4 DLT 0 - - AE 23 (92%) 6 (24%) 2 (8%) Related AE 13 (52%) 2 (8%) - SAE 8 (32%) 2 (8%) 2 (8%) Related SAE 2 (8%) †† - - AE causing treatment discontinuation 1 (4%) 1 (4%)* - Fatal AE 2 (8%)** n is the number of subjects havi
Slide 109: Adverse Events Related to Drug (Dose-Escalation)
ADVERSE EVENTS RELATED TO DRUG (DOSE-ESCALATION) (REPORTED BY ≥2 PATIENTS, DATA CUTOFF 5/SEPT/2017) Related AE (N = 25) All grades* Grade 3 Grade 4 n (%) n (%) n (%) Any related AE 13 (52) 3 (8) 0 Lymphopenia 4 (16) 2 (8) 0 Asthenia 3 (12) 0 0 Nausea 2 (8) 0 0 Chills 2 (8) 0 0 Pyrexia 2 (8) 0 0 Arth
Slide 110: Efficacy Outcome (Dose-Escalation)
EFFICACY OUTCOME (DOSE-ESCALATION) DATA CUT-OFF 5/SEPT/2017 Best Response Best Response in Sézary Syndrome patients in all patients Global Global Skin Blood N=25 n=20 n=20 n=20 Best Response (n) CR 1 1 2 5 PR 10 9 10 8 SD 12 8 8 6 PD 2 2 0 1 ORR 44 % 50 % 60 % 65 % ORR4, n (%) 9 (36%) 8 (40%) DOR (d
Slide 111: mSWAT Used to Measure Skin Tumor Burden in MF/SS
MSWAT (MODIFIED SEVERITY WEIGHTED ASSESSMENT TOOL) IS USED TO MEASURE SKIN TUMOR BURDEN IN MF/SS • Two assessments 1. Lesion assessment – patch, plaque or tumor 2. Body surface area involved • Calculate body surface area affected by patch, plaque and tumor • This is then multiplied by 1, 2, or 4 for
Slide 112: Maximum Percent Change in mSWAT Score and Aberrant Blood Cell Counts
MAXIMUM PERCENT CHANGE IN MSWAT SCORE AND ABERRANT BLOOD CELL COUNTS IN SÉZARY SYNDROME PATIENTS Skin RR = 60% Best Global Response: mSWAT score CR PR SD PD Aberrant blood cell count Blood RR = 65% IPH4102 113
Slide 113: Representative Pictures of Responders
REPRESENTATIVE PICTURES OF RESPONDERS • Patient 11-005: > 77-year old female > Sézary Syndrome (SS) diagnosed in NOV 2008 > 6 lines of previous therapies (incl. ECP + BEX + INFα, MTX, mogamulizumab, ECP + INFα + MTX, romidepsin, BEX+ INFα) > Started at 0.05 mg/kg on 25JAN16 > Global PR since W10 (0.
Slide 114: Exploratory/Pharmacodynamics Endpoints: Skin & Blood Assessments
EXPLORATORY/PHARMACODYNAMICS ENDPOINTS SKIN & BLOOD ASSESSMENTS / PT 11-005 CD4/8 mSWAT • Treated skin lesions show decrease in CD4 and increase SCR = screening ratio score in skin in CD8 lymphocytes SCR: 52% • Decrease in %KIR3DL2+ CD4 T-cells in skin/blood % of KIR3DL2+ cells in skin lesions by IH
Slide 115: Representative Pictures of Responders
REPRESENTATIVE PICTURES OF RESPONDERS • Patient 11-024: Screening > 75-year old male > SS diagnosed in AUG 2011 > 6 lines of previous therapies (incl. MTX, INFα, vorinostat then mogamulizumab, BEX, pembrolizumab) W28 Sustained PR > Started at 3 mg/kg on 16OCT16 > Global PR since W14 (3 mg/kg), susta
Slide 116: Significant Pruritus Improvement by VAS Score
SIGNIFICANT PRURITUS IMPROVEMENT BY VAS SCORE VAS: Visual Analogue Scale IPH4102 117
Slide 117: IPH4102-101 Summary (Dose Escalation)
IPH4102-101 SUMMARY (DOSE ESCALATION) SAFETY, CLINICAL ACTIVITY AND BIOMARKERS • IPH4102 Maximal Tolerated Dose was not reached: Recommended Ph 2 Dose is 10 mg/kg • Well-tolerated in heavily pretreated (med. 4 prior lines) advanced CTCL patients • Best global ORR is 44% in the overall population and
Slide 118: Acknowledgements
ACKNOWLEDGEMENTS All our patients and their families… Depts of Dermatology & Pathology Stanford Cancer Institute (CA, USA) St Louis Hospital (Paris, France) Youn H. Kim Martine Bagot Michael Khodadoust Caroline Ram-Wolff Ohio State University (OH, USA) Steve Mathieu Basem William Maxime Battistella
Slide 119: Next Generation IO – Monalizumab (NKG2A)
NEXT GENERATION IO 3 STRATEGIC KEY PILLARS 1 2 3 NK cells Tumor Tumor checkpoints targeting Microenvironment (NKCP) (TAg) (TME) monalizumab (target: NKG2A) Monalizumab 120
Slide 120: Monalizumab: Combination Strategy Opportunity
MONALIZUMAB COMBINATION STRATEGY OPPORTUNITY Mohammed Dar VP Oncology clinical development AstraZeneca MedImmune Monalizumab 121
Slide 121: Next-Generation Immuno-Oncology at AstraZeneca/MedImmune
NEXT-GENERATION IMMUNO-ONCOLOGY AT ASTRAZENECA/MEDIMMUNE BROAD IO CLINICAL PROGRAM TO ENHANCE ANTI-TUMOR IMMUNITY Monalizumab 122
Slide 122: Monalizumab (IgG4 Anti-NKG2A)
MONALIZUMAB (IGG4 ANTI-NKG2A) BLOCKS NKG2A/HLA-E MEDIATED SUPPRESSION OF NK CELLS AND CD8 T CELLS HLA-E on tumor cells NKG2A on TILs 100 P e r c e n ta g e o f p a tie n ts 75 50 25 0 0) 0) 0) 0) 6) *) 7) 7) =2 =4 =4 =4 =1 ) ( =4 =4 (n (n ) (n ) (n (n = 1 5 ) (n ) (n l ) l N ry or a ma a l (n a ma H
Slide 123: Rationale for Durvalumab & Monalizumab Combination
RATIONALE FOR DURVALUMAB & MONALIZUMAB COMBINATION: ENHANCE ANTI-TUMOR IMMUNITY BY NON-REDUNDANT, POTENTIALLY SYNERGISTIC PATHWAYS Anti-NKG2A _ NKG2A HLA-E - + Activating Activating + receptor ligand HLA-E MHC PD-L1 NKG2A _ TCR Anti-PD-L1 + _ PD-1 + or PD-1 Monalizumab 124
Slide 124: Monalizumab – Development Strategy
MONALIZUMAB – DEVELOPMENT STRATEGY ADDRESS SIGNIFICANT MEDICAL NEEDS 1 Potentiate existing responses – IO sensitive tumors 2 Reverse resistance to CPI – IO sensitive tumors 3 Unlock activity of NK and T cells – IO resistant tumors Monalizumab 125
Slide 125: Monalizumab – Joint Clinical Development Plan
MONALIZUMAB – JOINT CLINICAL DEVELOPMENT PLAN FOCUS ON COMBINATIONS AZ- Innate Pharma MedImmune Ovarian Single agent dose ranging study CRC NSCLC NSCLC Endometrial SCCHN SCCHN CLL Monalizumab + Monalizumab + Monalizumab + Monalizumab + Durvalumab Durvalumab Cetuximab Ibrutinib Monalizumab 126
Slide 126: Monalizumab – Ongoing Phase 1/2 Study, Durvalumab + Monalizumab
MONALIZUMAB – CLINICAL DEVELOPMENT PLAN ONGOING PHASE 1 STUDY, DURVALUMAB + MONALIZUMAB Data snapshot 09Feb2018. Database is open and data cleaning in progress; results subject to change Dose-Escalation Mona Mona Mona Mona Mona Dose 1 Q2W Dose 2 Q2W Dose 3 Q2W Dose 4 Q2W Dose 4 Q4W + Durva + Durva +
Slide 127: Monalizumab & Cetuximab Combination
MONALIZUMAB – CLINICAL DEVELOPMENT PLAN MONALIZUMAB & CETUXIMAB COMBINATION Rationale • High level of HLA-E expression in Evaluate safety and define SCCHN MTD/RP2D of mona+cetux • Cetuximab is approved in SCCHN, including in post-platinum setting • Cetuximab-mediated ADCC is inhibited Assess antitum
Slide 128: Key Development Questions for Monalizumab
KEY DEVELOPMENT QUESTIONS FOR MONALIZUMAB Understand which Assess potential to Understand potential pts likely to benefit combine with with tumor-targeting from Mona+Durva chemotherapy mAbs Ongoing analysis of paired tumor and blood samples Consider chemotherapy combination arms - Explore cetuximab
Slide 129: Market Potential and Pipeline Newsflow
MARKET POTENTIAL AND PIPELINE NEWSFLOW MONDHER MAHJOUBI CHIEF EXECUTIVE OFFICER
Slide 130: Building an Innovative & Differentiated Pipeline
INNATE PHARMA – PIPELINE BUILDING AN INNOVATIVE & DIFFERENTIATED PIPELINE No effective Anti-tumor immunity Sub-optimal or exhausted anti-tumor immunity suppressed by TME anti-tumor immunity Noninflamed Inflamed NK Bispecific IPH5401 Monalizumab Engagers Anti-C5aR Anti-NKG2A Antibody Drug IPH53 Liril
Slide 131: IPH4102 – Targeting T-Cell Lymphoma
IPH4102 – TARGETING T-CELL LYMPHOMA SÉZARY AS THE ENTRY POINT Increasing efficacy Combination Combination Monotherapy Monotherapy ATLL Sézary CTCL PTCL Expanding patient population 132
Slide 132: IPH4102 – Commercial Opportunity
IPH4102 – COMMERCIAL OPPORTUNITY SIGNIFICANT POTENTIAL BEYOND SÉZARY ATLL PTCL Advanced CTCL Sézary 850 pts 15000 pts 3200 pts 1000 pts* • 15% of all NHL • Highly heterogeneous • Medical need in late lines 1L 2L 3L** 3L+ • Differentiated profile • Biomarker driven therapy • Premium pricing strategy
Slide 133: Monalizumab – Combination Strategy
MONALIZUMAB – COMBINATION STRATEGY LEVERAGE NON REDUNDANT & SYNERGISTIC PATHWAYS Potentiate responses in IO Unlock responses in IO sensitive tumors resistant tumors SCCHN CRC Mona + Cetux 3L* Mona + Durva 2-4L Mona + Cetux + SoC 2L Mona + Durva + CT Mona + Cetux + RT/CT LA *3L: Potential fast to mar
Slide 134: Monalizumab – Commercial Opportunity: SCCHN Current Landscape
MONALIZUMAB – COMMERCIAL OPPORTUNITY IO SOC Other SOC SCCHN – CURRENT COMPETITIVE LANDSCAPE Resectable Unresectable Metastatic 1L 2L 35k* 40k* 65k* 25k* Cis-ineligible Cetuximab + RT 40% Adjuvant CT + Cetuximab IO Mono CT/RT Cis-eligible Cisplatin + RT 60% *Drug-treated patients in US/5EU/Jpn & Chin
Slide 135: Monalizumab – Commercial Opportunity: SCCHN Future Landscape
MONALIZUMAB – COMMERCIAL OPPORTUNITY IO SOC Other SOC SCCHN – FUTURE COMPETITIVE LANDSCAPE Resectable Unresectable Metastatic 1L 2L 3L 35k* 40k* 65k* 25k* 15k* Cis-ineligible Cetuximab + RT Adjuvant Mona + Cetux IO Combo IO Mono CT/RT Cis-eligible IO + RT/CT Mona + Cetux Mona + Cetux *Drug-treated p
Slide 136: Monalizumab – Commercial Opportunity: CRC
MONALIZUMAB – COMMERCIAL OPPORTUNITY CRC - THE NEXT BIGGEST OPPORTUNITY • Third most common cancer worldwide 2016 2026 • ~1.1m deaths by 2030 • High unmet need in the metastatic setting • Chemo + Bev or Cetux is SoC • Limited options in late lines • IO monotherapy approved in 3L MSI- high • Large ma
Slide 137: IPH5401 – Unlock the Immune Response
IPH5401– UNLOCK THE IMMUNE RESPONSE IN COMBINATION WITH ANTI PD/PD-L1 Tumor Incidence C5aR types * expression NSCLC 290K ~80% Reverse IO resistance UCC 50K ~70% Strategy Enhance IO response HCC 110K ~70% CRC 575K 60% Gastric 258K 30-35% Expand into IO refractory tumors TNBC 72K 13-27% Prostate 621K
Slide 138: IPH5401 – Commercial Opportunity: NSCLC
IPH5401 – COMMERCIAL OPPORTUNITY NSCLC – TREATING IO FAILURES Stage III-IV NSCLC* 2nd line IO-pretreated NSCLC US: 127k 260k EU5: 100k Patients Japan: 43k eligible 3rd line US: 53k EU5: 40k 110k • ~1.6m global lung cancer deaths Patients Japan: 17k eligible • IO transforming NSCLC management • Vast
Slide 139: IPH5401 – Commercial Opportunity: HCC
IPH5401 – COMMERCIAL OPPORTUNITY HCC – OPTIMIZING IO RESPONSE Advanced stage HCC* 1st line US: 5k 25k EU5: 10k Patients Japan: 10k treated 2nd line US: 5k 13k EU5: 5k Patients • >500,000 people affected Japan: treated • Third leading cause of cancer deaths 3k • Moderate activity of CPI * IO likely t
Slide 140: Innate Pharma – Long Term Catalysts
INNATE PHARMA – LONG TERM CATALYSTS IPH52 IPH52 combo IPH52 potential Ph 1 Ph 1/2 pivotal program* IPH5401 + Durva IPH5401 + PD1/L1 IPH43 IPH5401 potential IPH43 IPH43 potential Ph1/2 Ph2-3rd indication Ph 1/2 pivotal program* Ph 2/3 pivotal program* IPH4102 IPH4102 IPH4102 Pivotal-SS Ph 1/2 ATLL Pi
Slide 141: Upcoming Conference AACR 2018
UPCOMING CONFERENCE AACR 2018 INNATE PHARMA TO PRESENT NEW DATA FROM ITS IMMUNO-ONCOLOGY PORTFOLIO • Oral presentation of Eric Vivier, CSO, on next generation immunotherapies • 5 presentations by Innate Pharma teams, including: > Preliminary clinical efficacy data on monalizumab in combination with
Slide 142: Questions & Answers
QUESTIONS & ANSWERS
Slide 143: Closing Remarks
CLOSING REMARKS MONDHER MAHJOUBI CHIEF EXECUTIVE OFFICER
Slide 144: Key Messages
KEY MESSAGES World-class science and technology platform Clinical read-outs ahead for monalizumab and IPH4102 programs Delivering on IPH5401 with clinical collaborations to accelerate development Potential to address large unmet medical needs in cancer Financial strength, enabling room for investmen
Slide 145: Innate Pharma – Our Ambition
INNATE PHARMA – OUR AMBITION BUILDING IO LEADERSHIP 3 new Growing medicines pipeline by 2025 More partnerships Disciplined execution
Slide 146: Thank You
THE INNATE IMMUNITY COMPANY THANK YOU