Innate Pharma Sa Class A · EURONEXT:IPH
Innate Pharma Sa Class A — Investor Presentation (January 2017)
87 slides from Innate Pharma Sa Class A's investor presentation, January 2017
Slide 1: Novel Checkpoints in Immuno-Oncology: Company Presentation 1Q2017
NOVEL CHECKPOINTS IN IMMUNO-ONCOLOGY KIR2DL1,2,3 NKG2A NKP46 COMPANY KIR3DL2 PRESENTATION CD39 MICA/B CD73 1Q2017
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: Strong Foundations for Future Growth: 2016 Key Results
STRONG FOUNDATIONS FOR FUTURE GROWTH 2016: KEY RESULTS • ENCOURAGING DATA FOR ALL THREE FIRST-IN-CLASS CLINICAL CANDIDATES: LIRILUMAB, MONALIZUMAB AND IPH4102 > Validates Innate Pharma’s positioning and strategy in innate immunity modulation and NK cell biology > Supports ambition to be at forefront
Slide 4: Innate Pharma – Pioneer in NK Cells Checkpoint Inhibitors
INNATE PHARMA – PIONEER IN NK CELLS CHECKPOINT INHIBITORS Differentiated Science • Pioneered the discovery and development of NK cells checkpoint inhibitors in Immuno-Oncology • A new track in IO/IO combination therapies • 3 clinical-stage candidates addressing novel targets, including two Portfolio
Slide 5: Strategy to Become a Fully-Integrated Biopharmaceutical Company
STRATEGY TO BECOME A FULLY-INTEGRATED BIOPHARMACEUTICAL COMPANY R&D collaboration Global Co-development and In-House Development 2003 - 2009 Commercialization of IPH4102 (Ph I) Monalizumab (Ph II) Fully- integrated 1999 2010 2011 2015 2016 biopharma company Inception License Research and Licensing B
Slide 6: Developing a Broad and Diversified Antibody Portfolio
DEVELOPING A BROAD AND DIVERSIFIED ANTIBODY PORTFOLIO WITH NOVEL MECHANISMS OF ACTION PROGRAM TARGET INDICATION STAGE OWNERSHIP Acute Myeloid Leukemia - Single agent Phase II Licensed to Lirilumab KIR2DL-1,-2,-3 Solid and hematological tumors - Multiple 6 Exploratory Phase I & II trials Bristol-Myer
Slide 7: Upcoming Newsflow and Next Steps
UPCOMING NEWSFLOW AND NEXT STEPS PROGRAM NEWSFLOW / EVENTS EffiKIR Early 2017: Data on primary endpoint Lirilumab Combination with nivolumab in squamous cell 2017: Next steps in the development program Licensed to Bristol-Myers Squibb carcinoma of the head and neck (SCCHN) ……….. Other combination tr
Slide 8: Financial Highlights
FINANCIAL HIGHLIGHTS STRONG FINANCIAL POSITION • Well capitalized with cash, cash equivalents and financial assets* of €239.6m at the end of 3Q16 • At the end of 3Q16 cash consumption amounted to €34.1m, including €7.8m non recurrent In thousand euros (IFRS) June 30, 2016 June 30, 2015 *current and
Slide 9: Share Capital
SHARE CAPITAL KEY FIGURES AND ANALYST COVERAGE • Listed on Euronext, IPO in November 2006 10.3% > Euronext Paris: FR001331421 – IPH 8.2% • Stock liquidity (in 2016) 5.1% 2.6% > Average daily trading volume >300,000 73.8% > 54m outstanding shares (56.8 fully diluted) • Analyst coverage: > Bryan Garni
Slide 10: Management Team
MANAGEMENT TEAM Mondher MAHJOUBI Pierre DODION Laure-Hélène MERCIER Marcel ROZENCWEIG MD, MD, MBA, MSc, MBA, MD, Chief Executive Officer Chief Medical Officer Chief Financial Officer Chairman, Innate Pharma Inc. AstraZeneca, ARIAD, Pfizer, Novartis, Innate Pharma, Genentech, Roche Aventis Oddo Secur
Slide 11: Targeting NK Cells as a Therapeutic Approach
TARGETING NK CELLS AS A THERAPEUTIC APPROACH
Slide 12: NK Cells Exert Potent Anti-Cancer Functions
NK CELLS EXERT POTENT ANTI-CANCER FUNCTIONS MULTIPLE MECHANISMS OF ACTION FOR NK CELLS CD8 T cell • Direct cytotoxicity: Direct lysis > Kill tumors and stressed cells > Triggered by conserved stress- Activation Uptake of target antigens cell debris • Promote T cell responses: Direct lysis or ADCC >
Slide 13: Combinations of Checkpoint Blockers
COMBINATIONS OF CHECKPOINT BLOCKERS CAN LEAD TO DEEPER RESPONSES AND IMPROVED SURVIVAL 1 Source: Citi Research • Combination of ipilimumab plus nivolumab approved in melanoma showed some deeper and more durable responses compared to either agent alone2 1. Postow et al., NEJM 2015; 2. Larkin et al.,
Slide 14: Pioneer in NK Cells Checkpoint Inhibitors
PIONEER IN NK CELLS CHECKPOINT INHIBITORS NK CELL-BASED CANCER IMMUNOTHERAPIES Innate Pharma Anti-CD137 | BMS, Agonist mAB Checkpoint inhibitors CD16-targeting bispecifics | Affimed Bispecifics Lirilumab | IPH/BMS Monalizumab | IPH/AZN IL-12 - Celsion, Cytokine CEA-IL-2 | Roche, Antibody-IL2 fusion
Slide 15: Validation of Innate Pharma's NK Positioning
VALIDATION OF INNATE PHARMA’S NK POSITIONING 2H 2016: ENCOURAGING CLINICAL RESULTS FOR TWO FIRST-IN-CLASS ANTIBODIES Page 15
Slide 16: Lirilumab
LIRILUMAB FIRST-IN-CLASS ANTI-KIR MAB LICENSED TO BRISTOL-MYERS SQUIBB
Slide 17: Lirilumab Is a First-in-Class KIR Checkpoint Inhibitor
LIRILUMAB IS A FIRST-IN-CLASS KIR CHECKPOINT INHIBITOR MECHANISM OF ACTION AS SINGLE AGENT • Fully human antibody (IgG4) blocking NK cell inhibitory receptor KIR2DL-1,-2,-3 • Prevents interaction with HLA-C class I molecules to potentiate NK cell killing of tumor cells Anti-KIR NK cell Tumor cell _
Slide 18: Lirilumab in Combination with T Cell Checkpoint Inhibitors
LIRILUMAB IN COMBINATION WITH T CELL CHECKPOINT INHIBITORS COMPLEMENTARY MECHANISMS OF PD1 AND KIR BLOCKADE Anti-KIR NK cell Tumor cell _ KIR HLA-C - + Activating receptor Activating ligand + MHC PD-L1 TCR + _ PD-1 + - Anti-PD-1 or PD-L1 CD8 T cell + • Exploratory clinical program ongoing in several
Slide 19: Summary of Exploratory Clinical Program with Lirilumab
SUMMARY OF EXPLORATORY CLINICAL PROGRAM WITH LIRILUMAB NEARLY 700 PATIENTS TO RECEIVE LIRILUMAB PHASE PATIENTS INDICATION STATUS EffiKIR Acute Myeloid Leukemia Data on LFS expected Monotherapy Randomized Phase II 150 Maintenance setting early 2017 Phase I with dose escalation and Selected solid tumo
Slide 20: Epidemiology of SCCHN
EPIDEMIOLOGY OF SCCHN • SCCHN is the cancer with seventh highest prevalence globally > About 3% of all cancers > 600,000 cases diagnosed annually > Higher incidence in men • Vast majority are squamous cell carcinoma • 75% of SCCHN are related to cigarette smoking and alcohol > Particular case of HPV
Slide 21: Anti-PD-1/PD-L1 in Second Line R/M SCCHN
ANTI-PD-1/PD-L1 IN SECOND LINE R/M SCCHN REGULATORY STATUS • Keytruda > FDA: Accelerated approval granted for RM SCCHN with disease progression on or after platinum-containing chemotherapy. > EMA: Under review • Opdivo > FDA: Approved for RM SCCHN with disease progression on or after a platinum-base
Slide 22: Lirilumab + Nivolumab in SCCHN (Trial CA223-001)
LIRILUMAB + NIVOLUMAB IN SCCHN (TRIAL CA223-001) ELIGIBILITY CRITERIA AND TREATMENT SCHEDULE • Eligibility criteria for dose escalation and cohort expansion: > Advanced solid tumors; < 5 lines of prior therapy; > one in the escalation part > ECOG PS < 1 • Eligibility criteria specific to the SCCHN c
Slide 23: Treatment-Related Adverse Events (TRAEs)
TREATMENT-RELATED ADVERSE EVENTS (TRAES) ALL EXPANSION COHORTS COMBINED (TRIAL CA223-001) All Patients (N = 159) Patients with TRAE, n (%) Any Grade Grade 3/4 Any TRAE 114 (71.7) 24 (15.1) TRAEs in > 10% of all patients Fatigue 33 (20.8) 0 Pruritus 30 (18.9) 0 Infusion-related reaction 28 (17.6) 0 R
Slide 24: Demographics of Patients with SCCHN Treated
DEMOGRAPHICS OF PATIENTS WITH SCCHN TREATED LIRILUMAB + NIVOLUMAB (CA223-001) OR NIVOLUMAB (CHECKMATE 1411) Lirilumab + Nivolumab Nivolumab alone1 (n = 41)* (N = 240) ECOG PS, n (%)** 0 9 (22.0) 49 (20.4) 1 32 (78.0) 189 (78.8) ≥2 0 1 (0.4) Tumor location, n (%) Oral cavity 23 (56.1) 108 (45.0) Phar
Slide 25: Efficacy Data in CA223-001 and CheckMate 141
EFFICACY DATA IN CA223-001 AND CHECKMATE 141 IN EVALUABLE PATIENTS WITH SCCHN Lirilumab + Nivolumab Nivolumab alone1 ORR, n/N (%) 7/29 (24.1)* 32/240 (13.3) Complete response 3 (10.3)* 6 (2.5) Partial response 4 (13.8)* 26 (10.8) DCR, n/N (%) 15/29 (51.7) NR ORR by PD-L1 expression, n/N (%)† <1% 0/9
Slide 26: Maximum Percent Reduction in Target Lesions Over Time
PRELIMINARY MAXIMUM PERCENT REDUCTION AND PERCENT CHANGE FROM BASELINE IN TARGET LESIONS OVER TIME In evaluable patients with SCCHN treated with lirilumab + nivolumab (n = 26)* The median DOR was not reached *26 of 29 evaluable patients had a post-baseline assessment. a Patient with a 37% reduction
Slide 27: Lirilumab + Nivolumab in SCCHN: Conclusions
LIRILUMAB + NIVOLUMAB IN SCCHN CONCLUSIONS FROM PRELIMINARY DATA OF CA223-001 • This is the first report of efficacy with the anti-KIR agent lirilumab in combination with nivolumab • Potential for a differentiated profile in this patient population with enhanced clinical activity, particularly in in
Slide 28: Therapeutic Potential of NK Cells Demonstrated Clinically
THERAPEUTIC POTENTIAL OF NK CELLS DEMONSTRATED CLINICALLY CONTROL OF RESIDUAL DISEASE IN ACUTE MYELOID LEUKEMIA (AML) • Alloreactive NK cells can protect against tumor relapse, leading to improved survival in AML patients after haplo-identical HLA mismatch stem cell transplantation Effects are: • Du
Slide 29: Phase I with Hybridoma Anti-KIR (IPH2101)
PHASE I WITH HYBRIDOMA ANTI-KIR (IPH2101) TRENDS IN CLINICAL OUTCOME & KIR SATURATION • Elderly AML patients in complete remission (CR) after induction and consolidation treatment (maintenance setting) • Total of 35 patients: 23 in the dose escalation part and 12 in study extension; doses ranged fro
Slide 30: EffiKIR Positioning in Acute Myeloid Leukemia
EFFIKIR POSITIONING IN ACUTE MYELOID LEUKEMIA STRONG MEDICAL NEED IN ELDERLY PATIENTS Treatment paradigm • 5-year survival rate in elderly patients Patients <60y (<50%) Patients >60y (>50%) with AML is 5 to 15% ~ 50% ~ 50% • No current standard of care for elderly patients in post-induction setting
Slide 31: EffiKIR Phase II Trial
EFFIKIR PHASE II TRIAL DOUBLE-BLIND PLACEBO-CONTROLLED RANDOMIZED TRIAL IN AML • Target enrollment completed in July 2014 (150 patients); N=50 per arm • Treatment for 2 years • Primary endpoint: Leukemia-Free Survival (Independent Review Committee) • One active arm stopped in March 2015 upon DSMB re
Slide 32: Phase Ib/II of Lirilumab + 5-Azacytidine in Relapsed AML
PHASE IB/II OF LIRILUMAB + 5-AZACYTIDINE IN RELAPSED AML EARLY DATA FROM THE COMBINATION SHOW GOOD SAFETY PROFILE • Heavily pretreated patient population with relapsed AML > Poor prognosis and few therapeutic options • Full doses of azacytidine and lirilumab were well tolerated (75 mg/m² and 3 mg/kg
Slide 33: Lirilumab Value Proposition
LIRILUMAB VALUE PROPOSITION LICENSING AGREEMENT WITH BRISTOL-MYERS SQUIBB Development and • Bristol-Myers Squibb is funding the commercialization rights development of lirilumab licensed to Bristol-Myers Squibb • Bristol-Myers Squibb is investing in multiple Phase I/II combo studies • Good safety pr
Slide 34: Monalizumab
MONALIZUMAB FIRST-IN-CLASS ANTI-NKG2A MAB CO-DEVELOPMENT AND COMMERCIALIZATION AGREEMENT WITH ASTRAZENECA
Slide 35: Monalizumab Is a First-in-Class NKG2A Checkpoint Inhibitor
MONALIZUMAB IS A FIRST-IN-CLASS NKG2A CHECKPOINT INHIBITOR MECHANISM OF ACTION • NKG2A is an inhibitory receptor on tumor infiltrating CD8 T cell and NK cells • Prevents interaction with HLA-E molecules to potentiate NK cells and CD8 T cells anti-tumor activity Anti-NKG2A NK cell Tumor cell _ NKG2A
Slide 36: Clinical Development Plan Informed by HLA-E Expression
CLINICAL DEVELOPMENT PLAN INFORMED BY EXPRESSION OF HLA-E • HLA-E is expressed on a wide variety of tumor types: > Head & Neck (~80%)1, Ovarian (~90%)2, Endometrium, Colorectal (~75%)3, Cervix, Lung (>70%)4, Esophagus (>50%)5, CLL (>90%)6 • Restricted expression on normal tissues H L A - E e x p r e
Slide 37: Combining NK and T Cell Checkpoint Inhibitors
COMBINING NK AND T CELL CHECKPOINT INHIBITORS PRECLINICAL DEMONSTRATION WITH ANTI-NKG2A AND ANTI-PD-1 C o n tro l • NKG2A is induced on tumor NKG2A blockade A n ti-N K G 2 Aenhances the anti-tumor efficacy A n ti-P of D -1PD-1/PD-L1 inhibitors infiltrating PD-1+ CD8+ T cells as A n ti- N K G 2 A + A
Slide 38: Summary of Exploratory Clinical Program with Monalizumab
SUMMARY OF EXPLORATORY CLINICAL PROGRAM WITH MONALIZUMAB TRIALS CONDUCTED IN US AND EUROPE – UP TO 480 PATIENTS PHASE PATIENTS INDICATION LOCALIZATION STATUS Started Sept. 2015 Canada Preliminary data Monotherapy Phase I/II Up to 98 Gynecological cancers (Canadian Cancer presented at Trials Group) E
Slide 39: Dose-Ranging Part of Phase I/II Trial of Monalizumab
DOSE-RANGING PART OF PHASE I/II TRIAL OF MONALIZUMAB FIRST DATA SHOW FAVORABLE SAFETY PROFILE • Data from the dose-ranging part of a Phase I/II trial in gynecologic malignancies published at EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in November 2016 > 18 patients with advanc
Slide 40: Monalizumab Value Proposition
MONALIZUMAB VALUE PROPOSITION CO-DEVELOPMENT AND COMMERCIALIZATION AGREEMENT WITH ASTRAZENECA Global co-development and commercialization • Financial terms include cash agreement for Monalizumab payments to Innate Pharma of up to $1.275Bn $100m prior to • Initial clinical program ongoing: $250m init
Slide 41: IPH4102
IPH4102 FIRST-IN-CLASS ANTI-KIR3DL2 CYTOTOXICITY- INDUCING MAB IN-HOUSE DEVELOPMENT
Slide 42: Cutaneous T Cell Lymphoma (CTCL)
CUTANEOUS T CELL LYMPHOMA (CTCL) ORPHAN DISEASE WITH HIGH MEDICAL NEED • CTCL is a group of rare and heterogeneous cutaneous lymphomas of T cells with poor prognosis and few therapeutic options at advanced stages > ~6,000 patients in EU and US > The most common CTCL subtypes are Mycosis fungoides (M
Slide 43: IPH4102 Is a First-in-Class Cytotoxicity-Inducing Antibody
IPH4102 IS A FIRST-IN-CLASS CYTOTOXICITY-INDUCING ANTIBODY DEPLETING KIR3DL2+ CTCL TUMOR CELLS • KIR3DL2 is specifically expressed on cutaneous and circulating CTCL cells irrespectively of disease grade and on all subtypes > ~65% of all CTCL subtypes > Expressed by up to 95% of CTCL in certain aggre
Slide 44: Phase I Study of IPH4102
PHASE I STUDY OF IPH4102 DOSE ESCALATION AND COHORT EXPANSION IN KIR3DL2+ PATIENTS • Dose escalation: 10 dose levels of repeated and escalating administrations of IPH4102 (0.0001 to 10 mg/kg; 4 times QW, 10 times Q2W, until progression or unacceptable toxicity) • Cohort expansion: 2 cohorts of 10 pa
Slide 45: Preliminary Data from Dose Escalation Part of Phase I Trial
PRELIMINARY DATA FROM DOSE ESCALATION PART OF PHASE I TRIAL IPH4102 SHOWS GOOD SAFETY PROFILE1 • Preliminary results reported at 3WCCL2 and ASH 2016 on the first 7 dose levels (0.0001 to 1.5 mg/kg) > 16 patients evaluable for safety and efficacy (13 SS, 2 MF and 1 CD4+ CTCL) > Elderly and heavily pr
Slide 46: Encouraging Signs of Clinical Activity
ENCOURAGING SIGNS OF CLINICAL ACTIVITY COMPLETE RESPONSES APPEAR IN BLOOD AND SKIN IN SOME PATIENTS Illustration of a complete response in the skin in a 80 years old female with SS patient treated with IPH4102 Bagot et al., 3WCCL poster 2016 Page 46
Slide 47: Preclinical Pipeline and Technologies
PRECLINICAL PIPELINE AND TECHNOLOGIES
Slide 48: IPH4301 Is a First-in-Class Anti-MICA/B mAb
IPH4301 IS A FIRST-IN-CLASS ANTI-MICA/B MAB DUAL MECHANISM OF ACTION: ADCC AND IMMUNOMODULATION Melanoma Kidney carcinoma CRC (lung metastasis) • MICA/B are ligands for NKG2D receptors on NK cells and CD8+ T cells > Expression induced by stress, on a variety of highly prevalent solid tumors > Can be
Slide 49: Adenosine Pathway: Anti-CD39 and Anti-CD73
ADENOSINE PATHWAY: ANTI-CD39 AND ANTI-CD73 TARGETING IMMUNOSUPPRESSIVE TUMOR MICROENVIRONMENT T Cell Other immune cell Tumor Tumor depletion CD39 CD73 spreading NK cell AMP Anti-CD39 ATP Anti-CD73 Adénosine A2B receptor Activation ATP Immunosuppression P2X receptor CD8 or CD4 T cell Dendritic cell A
Slide 50: Proprietary Bispecific and ADC Technologies
PROPRIETARY BISPECIFIC AND ADC TECHNOLOGIES OPPORTUNITIES FOR PROPRIETARY PORTFOLIO EXPANSION NK Cell Engagers Antibody-Drug Conjugates Bispecific Antibodies Technology Proprietary ADC Technology • Trigger NK specific tumor killing through • Innovative conjugation technology NKp46 enabling homogenou
Slide 51: Moving Towards a Fully-Integrated Biopharmaceutical Company
MOVING TOWARDS A FULLY-INTEGRATED BIOPHARMACEUTICAL COMPANY • Pioneer in NK cells checkpoint inhibitors with broad and differentiated pipeline Investment • Encouraging results for two first-in-class antibody candidates Highlights • Partnerships with leading IO companies • Strong financial position a
Slide 52: Investor Relations
INVESTOR RELATIONS Laure-Hélène Mercier Chief Financial Officer investors@innate-pharma.com Tel: +33 (0)4 30 30 30 87
Slide 53: Appendix
APPENDIX Data on lirilumab P 56 Data on monalizumab P 62 Data on IPH4102 P 72 Data on other assets P 75 Technologies P 83
Slide 54: NK Checkpoint Blockade Enhances ADCC by Therapeutic Antibody
NK CHECKPOINT BLOCKADE ENHANCES ADCC BY THERAPEUTIC ANTIBODY DEMONSTRATION IN IN VIVO ASSAYS 1 • Similarly, ADCC by anti-CD20 and anti-EGFR is enhanced by combining with anti-KIR or anti-NKG2A2 1. Robbins et al., ASH 2014 poster; Sola et Al., ASH 2014 poster; 2. Kohrt et al., Blood, 2014; Internal d
Slide 55: Bibliography
BIBLIOGRAPHY TARGETING NK CELLS AS A THERAPEUTIC APPROACH > Guillerey et al., Targeting natural killer cells in cancer > Pittari et al., Revving up natural killer cells and cytokine- immunotherapy. induced killer cells against hematological malignancies Nat Immunol. 2016 Sept; 17 (9) 1025-1036 Front
Slide 56: Lirilumab Appendix
LIRILUMAB APPENDIX
Slide 57: Safety of Lirilumab
SAFETY OF LIRILUMAB WELL TOLERATED AS SINGLE AGENT IN HEMATOLOGIC AND SOLID TUMORS • Single agent Phase I with a variety of hematologic and solid tumors • 37 patients treated, at 6 dose levels from 0.015 mg/kg to 10 mg/kg • Well tolerated, no dose limiting toxicity, maximum tolerated dose not reache
Slide 58: Safety of Lirilumab in Combination with T Cell Checkpoint Inhibitors
SAFETY OF LIRILUMAB IN COMBINATION WITH T CELL CHECKPOINT INHIBITORS • Two Phase I trials of lirilumab plus nivolumab or ipilimumab • Conducted in patients with advanced solid tumors > Total of 181 patients enrolled in the two trials (incl. 159 for the lirilumab + nivolumab combo) > Lirilumab + nivo
Slide 59: Clinical Experience with Hybridoma Anti-KIR IPH2101
CLINICAL EXPERIENCE WITH HYBRIDOMA ANTI-KIR IPH2101 COMBINATION PHASE I IN MULTIPLE MYELOMA (MM) • Phase I dose escalation of IPH2101 in combination with lenalidomide (LEN) in 15 patients with relapsed/refractory MM > Prior therapies: one prior line: 10 patients; 2 prior lines: 5 patients; prior LEN
Slide 60: Lirilumab in Combination with Hypomethylating Agents
LIRILUMAB IN COMBINATION WITH HYPOMETHYLATING AGENTS • Hypomethylating agents are epigenetic modifiers • Two of these drugs have been approved: > 5-azacytidine (Vidaza®) • High risk myelodysplastic syndrome (MDS) (US and EU) • Palliative treatment of AML (EU) • Chronic myelomonocytic leukaemia (CMML
Slide 61: Bibliography
BIBLIOGRAPHY LIRILUMAB, ANTI-KIR > Curti et al., Larger size of donor alloreactive NK cell > Romagné et al., Preclinical characterization of 1-7F9, a repertoire correlates with better response to NK cell novel human anti-KIR receptor therapeutic antibody that immunotherapy in elderly acute myeloid l
Slide 62: Monalizumab Appendix
MONALIZUMAB APPENDIX
Slide 63: KIR and NKG2A Expression
KIR AND NKG2A EXPRESSION ON DIFFERENT SUBSETS OF NK CELLS • Blood NK cells from four healthy donors (one in each panel) stained for KIR and NKG2A Internal data Page 63
Slide 64: Tumor Infiltrating NK Cell Mostly Express NKG2A
TUMOR INFILTRATING NK CELL MOSTLY EXPRESS NKG2A NKG2A OFTEN INDUCED ON CD8+ T CELLS IN TUMORS Accumulation of NKG2A+ Induced expression of NKG2A on tumor NK cells inside tumors infiltrating CD8+ T cells Lung carcinoma1 Cervix cancer2 Blood NK (HC) Intratumoral NK Blood T cell Intratumoral T cell 1.
Slide 65: Monalizumab Phase I Safety Data
MONALIZUMAB PHASE I SAFETY DATA • Good safety profile in Phase I > Dose escalation safety trial in rheumatoid arthritis (RA) patients • 92 patients, mild to moderate severity RA, low-dose MTX (Methotrexate) • Intravenous (IV) single dose (up to 10 mg/kg) and subcutaneous (SC) single and multiple dos
Slide 66: Squamous Cell Carcinoma of the Head and Neck 1/2
SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK (SCCHN) 1/2 TREATMENT STRATEGY IN LOCALLY ADVANCED DISEASE • SCCHN is the sixth most common cancer worldwide1 (estimate) > 650,000 cases and 200,000 deaths/year worldwide, most common cancer in Asia1 > At diagnosis, 60% patients have locally advanced dise
Slide 67: Squamous Cell Carcinoma of the Head and Neck 2/2
SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK (SCCHN) 2/2 TREATMENT STRATEGY IN RECURRENT AND/OR METASTATIC SCCHN • Standard of care in recurrent and/or metastatic SCCHN: > Cetuximab only targeted agent approved is US and EU > As a single agent in this population, yields only modest activity (9% to 1
Slide 68: Ovarian Cancer
OVARIAN CANCER TREATMENT STRATEGY IN HIGH GRADE PRETREATED PATIENTS • 5th most common site of all cancers in women in the U.K., leading cause of death in gynecologic cancers1 > Overall incidence: 12/100,000 (21,290 estimated new cases in US in 2015)2 • Most common subtype is high grade serous carcin
Slide 69: Chronic Lymphocytic Leukemia (CLL)
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) TREATMENT STRATEGY IN RELAPSED OR REFRACTORY DISEASE • Most common form of leukemia, accounting for about 25% of all leukemias > Overall incidence: 15,720 new cases will occur in 2014 in the US, causing 4,600 deaths1 > Median age of diagnosis is 70 for males and 74
Slide 70: Bibliography
BIBLIOGRAPHY MONALIZUMAB, ANTI-NKG2A > Biology of CD94/NKG2A and HLA-E > Chronic Lymphocytic leukemia • Gunturi et al., The role of TCR stimulation and TGF- • Veuillen et al., Primary B-CLL resistance to NK cell beta in controlling the expression of CD94/NKG2A cytotoxicity can be overcome in vitro a
Slide 71: Bibliography
BIBLIOGRAPHY MONALIZUMAB, ANTI-NKG2A > Hematology, proof of concept > Lung carcinoma • Godal et al., NK cell killing of AML and ALL blasts by killer • Talebian Yazdi et al., The positive prognostic effect of cell Ig-like receptor-negative NK cells after NKG2A and stromal CD8+ tumor-infiltrating T ce
Slide 72: IPH4102, IPH4301, IPH52, Anti-CD73, IPH33 Appendix
IPH4102 IPH4301 IPH52 ANTI-CD73 IPH33 APPENDIX
Slide 73: IPH4102 Potent Anti-Tumor Activity in Models of Advanced CTCL
IPH4102 POTENT ANTI-TUMOR ACTIVITY IN MODELS OF ADVANCED CTCL • First-in-class cytotoxicity-inducing humanized antibody, aiming at depleting KIR3DL2 expressing cells RAJI-KIR3DL2 SC xenograft model Autologous ADCC with CTCL patient cells 2000 Patient #10 (representative of n = 15) **** Tumoral volum
Slide 74: Bibliography
BIBLIOGRAPHY IPH4102, ANTI-KIR3DL2 > Battistella M et al., KIR3DL2 (CD158k) is a potential > Agar et al., Survival outcomes and prognostic factors in therapeutic target in primary cutaneous anaplastic large cell mycosis fungoides/Sézary syndrome: validation of the lymphoma. revised International Soc
Slide 75: IPH4301 Preclinical Data Demonstrating Dual Mechanism of Action
IPH4301 PRECLINICAL DATA DEMONSTRATING DUAL MECHANISM OF ACTION Efficacy in mouse model of prostate IPH43-moIgG2a cures TRAMP-MICB mice from prostate cancer (TRAMP/MICB) cancer by restoring histology of prostate gland and inducing NK cell infiltration P=0.015 Control IPH43-moIG2A 2 .0 Normal / Cured
Slide 76: Bibliography
BIBLIOGRAPHY IPH4301 (ANTI-MICA/B) IPH4301, anti-MICA/B > Pahl et al., Antibody-dependent cell lysis by NK cells is preserved after sarcoma-induced inhibition of NK > Deng et al., A shed NKG2D ligand that promotes natural cell cytotoxicity. killer cell activation and tumor rejection. Cancer Immunol
Slide 77: IPH52 Novel, Potent Anti-CD39 Antibody
IPH52 NOVEL, POTENT ANTI-CD39 ANTIBODY • CD39 is expressed in several human cancers, including head & neck, lung, cervical, esophageal, sarcoma, liver, kidney, pancreatic, thyroid, endometrial tumors, as well as in lymphoma and melanoma Head & neck Cervix Liver Pancreas Soft tissue Squamous Cell Car
Slide 78: IPH52 Single Agent Activity in Preclinical Models
IPH52 SINGLE AGENT ACTIVITY IN PRECLINICAL MODELS VALIDATION Humanized mAb inhibits tumor growth in xenogeneic tumor model T u m o r g ro w th S u r v iv a l ** ** : p < 0 .0 0 0 1 1500 100 P e r c e n t s u r v iv a l T u m o r v o lu m e (m m ) 3 80 1000 60 500 40 20 0 0 10 20 30 40 0 10 20 30 40
Slide 79: IPH52 Potential for Combination with Cancer Treatments
IPH52 POTENTIAL FOR COMBINATION WITH CANCER TREATMENTS • CD39 disruption drives antitumor immune responses, either alone or in combination with PD-1 checkpoint inhibitors, ADCC antibodies and immunogenic chemotherapy, suggesting broad development potential Treatment with anti-PD1 and oxaliplatin in
Slide 80: Anti-CD73 Antibodies
ANTI-CD73 ANTIBODIES EFFICIENTLY REVERSE AMP-MEDIATED T CELL SUPPRESSION 80000 C T V o n t o t a l T c e ll s 60000 40000 • In an in vitro assay, T cell proliferation was inhibited by AMP, 3 0 0 0which can be converted ( M F I) 0 by CD73 to immunosuppressive adenosine 20000 10000 • This immunosuppre
Slide 81: IPH33, Anti-TLR3
IPH33, ANTI-TLR3 • Monoclonal antibody program that aims to block the toll-like receptor-3 (TLR3) > TLR3 is an inducer of pro-inflammatory cytokines and a participant in inflammatory feedback loops • Anti-TLR3 blocking, through antibody internalisation, may be used in a broad spectrum of chronic inf
Slide 82: Bibliography
BIBLIOGRAPHY IPH52, ANTI-CD73 & IPH33 IPH52, anti-CD39 IPH33, anti-TLR3 > Bastid et al., Inhibition of CD39 enzymatic function at the > Cavassani et al., TLR3 is an endogenous sensor of tissue surface of tumor cells alleviates their immunosuppressive necrosis during acute inflammatory events. activi
Slide 83: Technologies Appendix
TECHNOLOGIES APPENDIX
Slide 84: Proprietary Antibody-Drug Conjugates Technology
PROPRIETARY ANTIBODY-DRUG CONJUGATES TECHNOLOGY SITE-SPECIFIC CONJUGATION TECHNOLOGY FOR HOMOGENOUS ADC • New site-specific conjugation technology using bacterial transglutaminase (BTG) enzyme on an minimally modified antibody scaffold (single point mutation) • ADCs with DAR of exactly 2:1 or 4:1 Pa
Slide 85: Proprietary Antibody-Drug Conjugates Technology
PROPRIETARY ANTIBODY-DRUG CONJUGATES TECHNOLOGY SITE-SPECIFIC CONJUGATION TECHNOLOGY FOR HOMOGENOUS ADC • Stability ex vivo in human and cynomolgus plasma over one week • Stability and favorable pharmacokinetics in rat over 2 weeks • Efficacy validated in preclinical models • May be used for a broad
Slide 86: Bispecific Antibody Technology Engaging NK Cells
BISPECIFIC ANTIBODY TECHNOLOGY ENGAGING NK CELLS • Innovative bispecific antibody technology for engaging NK cells to kill tumor cells through NKp46 • NKp46 is an activating receptor expressed on all NK cells • NKp46-bispecific NK cell engagers brings tumor cells and NK cells together and trigger NK
Slide 87: Bibliography
BIBLIOGRAPHY ADC, NKP46 ADC TECHNOLOGY > Lhospice et al., Site-specific conjugation of monomethyl auristatin E to anti-CD30 antibodies improves their pharmacokinetics and therapeutic index in rodent models. Mol Pharm 2015 Jun 1;12(6):1863-71 > Panowksi et al., Site-specific antibody drug conjugates