Slide 1: Company Presentation 2Q2016
COMPANY PRESENTATION 2Q2016
Slide 2: Forward Looking Statement
FORWARD LOOKING STATEMENT This document has been prepared by Innate warranty or undertaking, express or implied, is Pharma S.A. (the “Company”) solely for the made as to, and no reliance should be placed on, purposes of a presentation to investors the fairness, accuracy, completeness or concerning t
Slide 3: Innate Pharma at a Glance
INNATE PHARMA AT A GLANCE Portfolio of first-in-class Differentiated science checkpoint inhibitors in Immuno-Oncology Innovative ADC and bispecific Partnerships with BMS, AZN, Sanofi antibody technologies Page 3
Slide 4: 2015: Creating the Platform for Growth
2015: CREATING THE PLATFORM FOR GROWTH • Strengthening the base > Landmark co-development and commercialization agreement with AstraZeneca for monalizumab in immuno-oncology > Initial clinical program of 5 trials implemented with monalizumab > Large ongoing clinical program with lirilumab • Building
Slide 5: Long Term Strategy
LONG TERM STRATEGY MOVING TOWARDS AN INTEGRATED BIOPHARMA COMPANY Global co-development and commercialization R&D 2015 collaboration Monalizumab (PII) 2003 - 2009 2010 2015 2020 1999 License Expansion of proprietary pipeline Inception 2011 • IPH4102 in-house development Lirilumab (PII) • In-licensin
Slide 6: Three Pillars of Developments
THREE PILLARS OF DEVELOPMENTS CLINICAL • 2 broad potential checkpoint inhibitors partnered PIPELINE with leaders in IO currently in Phase II • 1 Phase I proprietary cytotoxic mAb PRECLINICAL • Core focus in innate receptor pharmacology PIPELINE • Targeting T and NK effector cells and beyond • Novel
Slide 7: Innate Pharma Pipeline
INNATE PHARMA PIPELINE PROGRAM TARGET INDICATION STAGE Lirilumab Acute Myeloid Leukemia - Single agent Phase II Licensed to KIR2DL1,2,3 Bristol-Myers Squibb Solid & heme tumors - Multiple combinations 6 Phase I & II trials 0 Monalizumab Solid & heme tumors - Single agent and multiple Co-development
Slide 8: Expected Newsflow in 2016-2017
EXPECTED NEWSFLOW IN 2016-2017 PROGRAM MAIN NEWS 2015/2016 NEXT STEPS Lirilumab Effikir & combination in solid tumors on track License to Start of clinical trials read-out in 2016 Bristol-Myers Squibb 5 new combination trials in heme malignancies 0 Monalizumab First data in 2017 Co-development with
Slide 9: Targeting NK Cells as a Therapeutic Approach
TARGETING NK CELLS AS A THERAPEUTIC APPROACH
Slide 10: Innate Pharma Value Proposition
INNATE PHARMA VALUE PROPOSITION CHECKPOINT INHIBITION BEYOND PD-1 PATHWAY BLOCKADE • Heterogeneity in cancers, between patients or intra tumoral opens opportunity for differentiated novel agents Patient stratification and Combination therapy • Multiple agents needed to address large population of pa
Slide 11: Targeting NK Cells
TARGETING NK CELLS Anti-CD137 | BMS, Agonist mAB CD16-targeting bispecifics | Affimed Checkpoint inhibitors: NKp46-targeting bispecifics | Innate Lirilumab | IPH/BMS Bispecifics Monalizumab | IPH/AZN IL-12 - Celsion, Cytokine Innate Pharma CEA-IL-2 | Roche, Antibody-IL2 fusion proteins CARNK cells |
Slide 12: NK Cells Exert Potent Anti-Cancer Functions
NK CELLS EXERT POTENT ANTI-CANCER FUNCTIONS Uptake of target Stressed cells cell debris • Direct cytotoxicity: mDC > Kill tumors and infected cells Maturation > Triggered by conserved stress- antigens Activation • Cytokine production: > e.g. IFN- and IL-2 that Direct lysis or ADCC stimulate T cells
Slide 13: Therapeutic Potential of NK Cells
THERAPEUTIC POTENTIAL OF NK CELLS REVEALED IN ACUTE MYELOID LEUKEMIA • NK cells can protect against tumor relapse, leading to improved survival in AML patients after stem cell transplantation Effects are: • Durable NK activation • Safe NK inhibition • Mediated by NK cells • Controlled by KIR Velardi
Slide 14: Lirilumab
LIRILUMAB FIRST-IN-CLASS ANTI-KIR MAB LICENSED TO BRISTOL-MYERS SQUIBB
Slide 15: Licensing Agreement with Bristol-Myers Squibb
LICENSING AGREEMENT WITH BRISTOL-MYERS SQUIBB Development and commercialization rights licensed to Bristol-Myers Squibb $35m Up to $430m upfront at in milestone signing (2011) payments Double-digit royalties Page 15
Slide 16: Lirilumab
LIRILUMAB FIRST-IN-CLASS NK CELL CHECKPOINT INHIBITOR • Fully human antibody (IgG4) blocking NK cell inhibitory receptor KIR2DL1/2/3 • Prevents interaction with HLA class 1 molecules to potentiate NK anti-tumor activity Anti-KIR KIR HLA-C KIR HLA-C NK cell Tumor cell + Activating Activating ligand +
Slide 17: EffiKIR Phase II Trial
EFFIKIR PHASE II TRIAL DOUBLE-BLIND PLACEBO-CONTROLLED RANDOMIZED TRIAL IN AML • Target enrollment completed in July 2014 (150 patients) • Data on LFS expected 2H16 • One active arm stopped in March 2015 upon DSMB recommendation > DSMB considered that treatment in the stopped arm could not be superi
Slide 18: Clinical Program with Lirilumab
CLINICAL PROGRAM WITH LIRILUMAB SETTING PATIENTS INDICATION STATUS Data on LFS Randomized Acute Myeloid Leukemia Monotherapy 150 expected Phase II Maintenance setting 2H 2016 Phase I with cohort Selected solid tumors: Enrollment close Nivolumab 162 expansion MEL, NSCLC, GI, SCCHN, HCC to completion
Slide 19: Monalizumab
MONALIZUMAB FIRST-IN-CLASS ANTI-NKG2A MAB CO-DEVELOPMENT AND COMMERCIALIZATION AGREEMENT WITH ASTRAZENECA
Slide 20: Co-development and Commercialization Agreement with AstraZeneca
CO-DEVELOPMENT AND COMMERCIALIZATION AGREEMENT WITH ASTRAZENECA Global co-development and commercialization agreement for monalizumab $100m $250m initial payment prior to initiation of Phase III (June 2015) up to $925m additional milestones Co-promotion rights in Double-digit Europe royalties (50% p
Slide 21: Monalizumab Targets NKG2A Checkpoint on NK and CD8 T Cells
MONALIZUMAB (IPH2201) TARGETS NKG2A CHECKPOINT ON NK AND CD8 T CELLS • NKG2A is an inhibitory receptor on tumor infiltrating CD8 T cells and NK cells Anti-NKG2A NKG2A HLA-E NK cell Tumor cell + Activating Activating ligand + receptor HLA-E MHC NKG2A Anti-NKG2A TCR T cell NK and T cell inhibition by
Slide 22: NKG2A Is Expressed on Tumor Infiltrating Lymphocytes
NKG2A IS EXPRESSED ON TUMOR INFILTRATING LYMPHOCYTES Upregulation of NKG2A NKG2A on tumor infiltrating on NK cells inside tumors CD8+ T cells Lung carcinoma Cervical cancer Blood NK (HC) Intratumoral NK Blood T cell Intratumoral T cell From L to R : Platonova et al. 2011, Sheu et al. 2005 Page 22
Slide 23: Clinical Development Plan Informed by Expression of HLA-E
CLINICAL DEVELOPMENT PLAN INFORMED BY EXPRESSION OF HLA-E • Many tumors overexpress HLA-E, the ligand of NKG2A, suggesting a major mechanism of immune evasion • HLA-E upregulated on a wide variety of tumor types > Ovarian (>70%)1, Head and Neck (~80%)2, Colorectal (>80%), Lung (40%), CLL (>90%)3, Oe
Slide 24: Monalizumab Initial Clinical Development Plan
MONALIZUMAB INITIAL CLINICAL DEVELOPMENT PLAN TO GENERATE DATA IN 2017 SETTING PATIENTS INDICATION STATUS LOCALIZATION Head & Neck Started Dec. Monotherapy Phase I/II 43 Europe Neo-adjuvant setting 2014 Ovarian cancer Started Sept. Monotherapy Phase I/II 38 High grade platinum Canada 2015 sensitive
Slide 25: IPH4102
IPH4102 FIRST-IN-CLASS ANTI-KIR3DL2 CYTOTOXIC MAB IN-HOUSE DEVELOPMENT
Slide 26: Cutaneous T Cell Lymphoma
CUTANEOUS T CELL LYMPHOMA ORPHAN DISEASE WITH HIGH MEDICAL NEED • CTCL is a heterogeneous group of T-cell NHL presenting primarily in the skin > ~6,000 patients in EU and US > Mycosis fungoides (MF) and Sézary syndrome (SS), its leukemic variant, are the most common CTCL subtypes > Overall survival
Slide 27: KIR3DL2 Is Specifically Expressed on CTCL Cells
KIR3DL2 IS SPECIFICALLY EXPRESSED ON CUTANEOUS AND CIRCULATING CTCL CELLS • Irrespectively of disease grade and on most subtypes > ~65% of all CTCL; > Expression is more prominent in Sézary syndrome, transformed mycosis fungoides and CD30+ LPD (ALCL subtype): from 80% to 100% of patients • Restricte
Slide 28: Potent Antitumor Activity of IPH4102 in Models of Advanced CTCL
POTENT ANTITUMOR ACTIVITY OF IPH4102 IN MODELS OF ADVANCED CTCL • Humanized cytotoxic IgG1 RAJI-KIR3DL2 SC xenograft model Autologous ADCC with CTCL patient cells Patient #10 (representative of n = 15) 2000 **** Tumoral volume (mm 3) 100 IPH4102 1500 80 rituximab %7AAD+ CD4+ Isotype control Sézary c
Slide 29: Phase I Study of IPH4102 Started in 2015
PHASE I STUDY OF IPH4102 STARTED IN 2015 • Dose-escalation + cohort expansion • EU and US, involving referral expert study: centers: > Dose-escalation: 10 dose levels of > St Louis Hospital, Paris (Pr M. Bagot) repeated administrations of IPH4102 > UMC Leiden, the Netherlands (Dr M. > Cohort expansi
Slide 30: Discovery
DISCOVERY IPH43 (ANTI- MICA/B) ANTI-CD39 ANTI-CD73
Slide 31: IPH43 First-in-Class Anti-MICA/B mAb
IPH43 FIRST-IN-CLASS ANTI-MICA/B MAB • MICA/B is a ligand for the activating receptor NKG2D expressed on NK cells and CD8+ T cells. Its expression is induced upon tumoral transformation A. B. Tissue Positive/Total cases % Positive A. Breast Cancer 24/29 83% B. Colo-rectal 17/28 61% Cancer C. D. C. L
Slide 32: Adenosine Pathway: Anti-CD39 & Anti-CD73
ADENOSINE PATHWAY: FIRST-IN-CLASS ANTI-CD39 & ANTI-CD73 CHECKPOINT INHIBITOR PROGRAMS ATP Treg ATP Treg Other CD39 Other immune AMP immune CD39 cell cell CD73 ATP CD73 Anti-CD39 AMP Anti-CD73 Tumor Tumor ATP depletion NK spreading Adenosine NK Immunosuppression activation TCD8 TCD4 P2X receptor TCD8
Slide 33: Key Corporate and Financial Facts
KEY CORPORATE AND FINANCIAL FACTS
Slide 34: Key Figures
KEY FIGURES Year ended December 31 In thousand euros (IFRS) 2015 2014 Revenue and other income 25,141 7,623 Research and development expenses (29,906) (22,671) General and administrative expenses (6,008) (4,918) Net operating expenses (35,914) (27,589) Operating income / (loss) (10,772) (19,966) Fin
Slide 35: Share Information
SHARE INFORMATION • Listed on Euronext, IPO in November 2006 10.2% > Euronext Paris: FR0010331421 – IPH 8.3% 2.3% > Unsponsored ADR: INNTY • Stock liquidity (in 2015) 79.2% > Average daily trading volume >300,000 > 53.8m outstanding shares (55.7 fully diluted) • Analyst coverage: Novo Nordisk A/S* >
Slide 36: Management Team
MANAGEMENT TEAM Hervé Jérôme Pierre Marcel BRAILLY TIOLLIER DODION ROZENCWEIG PhD, PhD, MD, MBA, MD, CEO & Co-founder Chief Development Chief Medical President, Innate Officer Officer Pharma Inc. Immunotech SA, Pasteur Merieux ARIAD, Pfizer, Beckman-Coulter Sangstat Novartis, Aventis BMS Catherine N
Slide 37: Investor Relations
INVESTOR RELATIONS Laure-Hélène Mercier Sr Director, Investor relations investors@innate-pharma.com Tel: +33 (0)4 30 30 30 87 Fax: +33 (0)4 30 30 30 30
Slide 38: Appendix
APPENDIX Data on lirilumab P 39 Data on monalizumab P 47 Data on other assets P 54 & technology
Slide 39: Lirilumab Appendix
LIRILUMAB APPENDIX
Slide 40: Phase I with Lirilumab
PHASE I WITH LIRILUMAB • Single-agent Phase I with a variety of hematologic and solid tumors > Slowly progressive or stable disease or in complete response > Does not allow assessment of tumoral response • Primary endpoint: safety; secondary endpoints: PK/PD • 37 patients treated, at 6 dose levels f
Slide 41: Clinical Experience with Hybridoma Anti-KIR IPH2101
CLINICAL EXPERIENCE WITH HYBRIDOMA ANTI-KIR IPH2101 PHASE I IN ACUTE MYELOID LEUKEMIA • Elderly AML patients in complete remission after induction and consolidation treatment - maintenance setting • Phase I dose-escalation including 23 patients in first CR, and extension including 12 patients • Dose
Slide 42: Clinical Experience with Hybridoma Anti-KIR IPH2101
CLINICAL EXPERIENCE WITH HYBRIDOMA ANTI-KIR IPH2101 COMBINATION PHASE I IN MULTIPLE MYELOMA • Phase I dose-escalation of IPH2101 in combination with lenalidomide (LEN) in 15 patients with relapsed/refractory MM > Prior therapies: one prior line: 10 pts; 2 prior lines: 5 pts; prior LEN: 10 pts • Trea
Slide 43: EffiKIR Positioning in Acute Myeloid Leukemia
EFFIKIR POSITIONING IN ACUTE MYELOID LEUKEMIA STRONG MEDICAL NEED IN ELDERLY PATIENTS • 5-year survival rate in elderly Treatment paradigm patients with AML is 5 to 15% Patients <60y (<50%) Patients >60y (>50%) ~ 50% ~ 50% • No current standard of care for elderly patients in post- Induction chemoth
Slide 44: Lirilumab Enhances ADCC Function of NK Cells
LIRILUMAB ENHANCES ADCC FUNCTION OF NK CELLS In vivo effects of KIR blockade (lirilumab) on elotuzumab activity in xenograft tumor model Robbins et al., Poster ASH 2014 Page 44
Slide 45: Lirilumab in Combination with Hypomethylating Agents
LIRILUMAB IN COMBINATION WITH HYPOMETHYLATING AGENTS • Hypomethylating agents are epigenetic modifiers • 2 of these drugs have been approved: > 5 azacytidine in high risk myelodysplastic syndrome (MDS) (US and EU) > decitabine as palliative treatment of acute myeloid leukemia (US only) • These agent
Slide 46: Bibliography
BIBLIOGRAPHY LIRILUMAB, ANTI-KIR > Curti et al, 2016. Larger size of donor alloreactive NK cell repertoire correlates with better response to NK cell immunotherapy in elderly acute myeloid leukemia patients. Clinical Cancer Research > Benson et al., 2015, A phase I trial of the anti-KIR antibody IPH
Slide 47: Monalizumab Appendix
MONALIZUMAB APPENDIX
Slide 48: KIR and NKG2A Expression on Different Subsets of NK Cells
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 48
Slide 49: Monalizumab Phase I Safety Data
MONALIZUMAB PHASE I SAFETY DATA • Good safety profile in Phase I → Dose-escalation safety trial in rheumatoid arthritis patients - 92 pts, mild to moderate severity RA, low-dose MTX - IV single dose (up to 10 mg/kg) and SC single and multiple doses (up to 4 mg/kg) - No safety issues identified, MTD
Slide 50: Squamous Cell Carcinoma of the Head and Neck
SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK (SCCHN) TREATMENT STRATEGY IN LOCALLY ADVANCED DISEASE • SCCHN is the sixth most common cancer worldwide1 (estimate) > 650,000 cases and 200,000 deaths /yr worldwide, most common cancer in Asia1 > At diagnosis, 60% patients have locally advanced disease;
Slide 51: Ovarian Cancer
OVARIAN CANCER TREATMENT STRATEGY IN HIGH GRADE PRETREATED PATIENTS • 5th most common site of all cancers in women, leading cause of death in gynecologic cancers > Overall incidence : 12/100,000 (21,290 estimated new cases in US in 2015) • Most common subtype is high grade serous carcinoma (~60% of
Slide 52: Chronic Lymphocytic Leukemia
CHRONIC LYMPHOCYTIC LEUKEMIA 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 deaths (Siegel, Ma et al., 2014) > Median age of diagnosis is
Slide 53: Bibliography
BIBLIOGRAPHY MONALIZUMAB, ANTI-NKG2A > Wieten et al., 2014 Clinical and immunological significance of HLA-E in stem cell transplantation and cancer. Tissue Antigen > Zeestraten et al., 2014. Combined analysis of HLA class I, HLA-E and HLA-G predicts prognosis in colon cancer patents. Britsh Journal
Slide 54: Other Assets & Technology
OTHER ASSETS & TECHNOLOGY
Slide 55: IPH33, Proprietary Preclinical Asset
IPH33, PROPRIETARY PRECLINICAL ASSET A BLOCKING MAB TARGETING TLR3 • Blocking TLR3 aims at preventing inflammatory cytokine production, upstream of current treatments for inflammation > Major inducer of type I IFN and inflammatory cytokines (IL-6, TNF) > Overexpressed on inflammatory epithelial cell
Slide 56: IPH33, Proprietary Preclinical Asset
IPH33, PROPRIETARY PRECLINICAL ASSET A BLOCKING MAB TARGETING TLR3 • Mouse model of LPS+Elastase induced COPD Neutrophils Infiltrat infiltration de Neutrophiles in lungs dans les Poumons Lung tissue Destruction destruction Tissulaire dans les Poumons 8 10 0 5 1.010 2 cell number in BAL Destructio
Slide 57: Bibliography
BIBLIOGRAPHY IPH4102, IPH43 & IPH33 IPH4102, anti-KIR3DL2 > Sicard et al., 2014. IPH4102, a Humanized KIR3DL2 Antibody with Potent Activity against Cutaneous T-cell Lymphoma. Cancer Research > Bouaziz et al., 2010. Absolute CD3+ CD158k+ lymphocyte count is reliable and more sensitive than cytomorpho
Slide 58: 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 59: 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 s
Slide 60: 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