Slide 1: Company Presentation 1Q2015
COMPANY PRESENTATION 1Q2015
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 • Leading scientific edge in innate immunity pharmacology • Portfolio of first-in-class immunomodulating mAbs • Primary focus in immuno- oncology • Potential for developments in chronic Inflammation mAb: monoclonal antibody Page 3
Slide 4: Main News in 2014 / What to Expect in 2015
MAIN NEWS IN 2014 /WHAT TO EXPECT IN 2015 Lirilumab • EffiKIR Phase II on track Lirilumab clinical trials • Liri + nivo combination solid tumors on track read-out • 2 new combination trials in heme malignancies IPH2201 • Acquisition of full rights to IPH2201 IPH2201 Phase II trials • First patient i
Slide 5: Innate Pharma Pipeline
INNATE PHARMA PIPELINE PROGRAM TARGET INDICATIONS AND SETTING ONGOING STUDIES Lirilumab AML, single agent • Randomized Phase II (IPH2102/BMS-986015) KIR2DL1,2,3 licensed to Solid & heme tumors • 3 Phase I Bristol-Myers Squibb Multiple combinations IPH2201 NKG2A Head and Neck single agent • Phase II
Slide 6: Clinical Pipeline of Immunomodulating mAbs in Cancer
CLINICAL PIPELINE OF IMMUNOMODULATING MABS IN CANCER TARGET PHASE I PHASE II PHASE III MARKET CTLA-4 AZN BMS Checkpoint inhibitors PD-1 AZN BMS/ONO, Merck PD-L1 BMS Pfizer/Merck KGaA Roche, AZN KIR IPH/BMS NKG2A IPH LAG-3 BMS CD137 Pfizer, BMS Agonist antibodies B7-H3 Servier/MGNX CD40 Roche OX40 AZ
Slide 7: Innate Pharma Value Proposition
INNATE PHARMA VALUE PROPOSITION FIRST-IN-CLASS AGENTS IN IMMUNO-ONCOLOGY • Heterogeneity in cancers, between patients or intra tumoral opens opportunity for differentiation for novel agents Patient stratification and Combination therapy • Multiple agents needed to address large population of patient
Slide 8: Lirilumab
LIRILUMAB FIRST-IN-CLASS ANTI-KIR MAB
Slide 9: Therapeutic Potential of NK Cells in Acute Myeloid Leukemia
THERAPEUTIC POTENTIAL OF NK CELLS 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 • Controlled by KIR NK inhibition • Mediated by NK cells Velardi et al.,
Slide 10: Lirilumab: First-in-Class NK Cell Checkpoint Inhibitor
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 • Development and commercialization rights licensed to Bristol-Myers Squibb • $3
Slide 11: Rationale for Combining Lirilumab and T-Cell Checkpoint Agents
RATIONALE FOR COMBINING LIRILUMAB AND T-CELL CHECKPOINT AGENTS Activation through KIR blockade Anti-KIR KIR NK cell Tumor cell + Stimulation of T cells by NK cells Anti-PD-1 PD-1 T-cell Activation through PD-1 blockade Page 11
Slide 12: Lirilumab Enhances ADCC Function of NK Cells
LIRILUMAB ENHANCES ADCC FUNCTION OF NK CELLS Robbins et al., Poster ASH 2014 Page 12
Slide 13: Ongoing Clinical Program with Lirilumab
ONGOING CLINICAL PROGRAM WITH LIRILUMAB PATIENTS SETTING INDICATION STATUS (PLANNED) Randomized Acute Myeloid Leukemia LFS expected Monotherapy 150 Phase II Maintenance setting end of 2015 Enrollment Phase I with Selected solid tumors: Nivolumab 162 close to cohort expansion MEL, NSCLC, GI, SCCHN, H
Slide 14: Ongoing Clinical Program with Lirilumab
ONGOING CLINICAL PROGRAM WITH LIRILUMAB • 4 ongoing trials with lirilumab > 400+ patients, heme & solid tumors, single-agent and combinations • Multiple rationale of NK cell activation explored > Direct cytotoxic activity > Interplay with T cells > ADCC enhancement • Well tolerated in Phase I trial
Slide 15: 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 end of 2015 (100 events) 1:1:1 R Minimization A Lirilumab 0.1 mg/kg q 12 weeks N Intermittent full KIR occupancy Elderly Center D 1st comple
Slide 16: IPH2201
IPH2201 FIRST-IN-CLASS ANTI-NKG2A MAB
Slide 17: IPH2201 Targets NKG2A Checkpoint Inhibitory Receptor on NK and CD8 T Cells
IPH2201 TARGETS NKG2A CHECKPOINT INHIBITORY RECEPTOR ON NK AND CD8 T CELLS • NKG2A is a 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 inhibitio
Slide 18: Many Tumors Overexpress NKG2A Ligand
MANY TUMORS OVEREXPRESS NKG2A LIGAND SUGGESTING A MAJOR MECHANISM OF IMMUNE EVASION • HLA-E upregulated on a wide variety of tumor types Page 18
Slide 19: Phase II Program
PHASE II PROGRAM Indication Planned trials combination with SCCHN Single agent cetuximab if activity combination with Ovarian cancer Single agent signal standard chemotherapy CLL Combination with ibrutinib • Indications with high expression of HLA-E • Potential for well defined, rapid path to regist
Slide 20: Rationale for Testing IPH2201 in SCCHN
RATIONALE FOR TESTING IPH2201 IN SCCHN • HLA-E is expressed in about 80% of patients with squamous cell carcinoma of the head and neck (SSCHN) • HLA-E expression associated with histopath grade of laryngeal tumors1 HLA-E immunoperoxidase staining of laryngeal specimen (in brown)1 Normal laryngeal ti
Slide 21: NKG2A Expression in SCCHN and NK Activation by IPH2201
NKG2A EXPRESSION IN SCCHN AND NK ACTIVATION BY IPH2201 SCCHN tumor infiltrating NK activation by SCCHN lymphocytes express NKG2A1 cells enhanced by IPH22012 %CD137+ on NKG2A+ cells 1.Katou F, Cancer Res 2007; 2. internal data Page 21
Slide 22: Phase II of IPH2201 as Single Agent in Pre-Operative OSCC Patients
PHASE II OF IPH2201 AS A SINGLE AGENT IN PRE-OPERATIVE PATIENTS WITH OSCC • treatment-naïve pre-operative patients with Population resectable intermediate or high risk (stage III-IVa) • First 6 patients: IPH2201 at 4 mg/kg q2w x 4 Dose • Subsequent patients: IPH2201 at 10 mg/kg q2w x 4 Planned enrol
Slide 23: IPH4102
IPH4102 FIRST-IN-CLASS ANTI-KIR3DL2 CYTOTOXIC MAB
Slide 24: KIR3DL2 Is Specifically Expressed on Cutaneous and Circulating CTCL Cells
KIR3DL2 IS SPECIFICALLY EXPRESSED ON CUTANEOUS AND CIRCULATING CTCL CELLS • Irrespectively of disease grade and on most subtypes • Restricted expression on normal tissues Patients biopsies stained with Innate’s anti-KIR3DL2 mAb SS pt #1, grade IIIB tMF pt #1, grade IIB CD30+ LPD pt #3, grade IB 86.5
Slide 25: Potent Antitumor Activity in Models of Advanced CTCL
POTENT ANTITUMOR ACTIVITY IN MODELS OF ADVANCED CTCL • Humanized cytotoxic IgG1 • Start of Phase I expected in 2015 • Orphan drug status in EU for the treatment of cutaneous T-cell lymphoma RAJI-KIR3DL2 SC xenograft model Autologous ADCC with CTCL patient cells Patient #10 (representative of n = 15)
Slide 26: Key Corporate and Financial Facts
KEY CORPORATE AND FINANCIAL FACTS
Slide 27: Key Figures
KEY FIGURES 6-months ended June In thousands of euros (IFRS) 2014 2013 Current revenue and other income 4,137 6,978 Research and development (10,890) (7,003) General and administrative (2,310) (2,152) Operating expenses (13,200) (9,155) Operating income/(loss) (9,063) (2,177) Financial income, net,
Slide 28: Share Information
SHARE INFORMATION 10,2% • Listed on Euronext, IPO in November 2006 9,3% > Euronext Paris: FR0010331421 – IPH 7,9% > €178m raised since inception 57,5% 7,3% • Stock liquidity (in 2014) 5,9% 1,9% > 53.0m outstanding shares (54.4m diluted) > Average daily trading volume >300,000 Novo Nordisk A/S * BPIf
Slide 29: Appendix
APPENDIX
Slide 30: 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 31: 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 IPH201 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 • Treat
Slide 32: 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 measurement of tumoral response • Primary endpoint: safety > Secondary endpoints: PK/PD • 6 dose levels from 0.015 mg/kg to 10
Slide 33: 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 34: 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 26% 49% 2% 5% 25% 44% 36% 23% KIR 30% 36% 10% 12% 25% 33% 34% 20% NKG2A Internal data Page 34
Slide 35: NKG2A Expression on Tumor Infiltrating Lymphocytes
NKG2A EXPRESSION ON TUMOR INFILTRATING LYMPHOCYTES Upregulation of NKG2A NKG2A on tumor infiltrating on NK cells inside tumors CD8+ T cells Lung carcinoma Cervical cancer Blood Tumor Blood NK (HC) Intratumoral NK From L to R : Platonova et al. 2011, Sheu et al. 2005 Page 35
Slide 36: SCCHN: Treatment Strategy in Locally Advanced Disease
SCCHN TREATMENT STRATEGY IN LOCALLY ADVANCED DISEASE • Sixth most common cancer worldwide1 (estimate) > 650,000 cases and 200,000 deaths /yr worldwide, most common cancer in Asia1 • US: about 42,440 new cases and 8,390 deaths in 20142 • EU: 139,000 new cases / yr3 and > 68000 death /yr1 • At diagnos
Slide 37: IPH2201 Phase I Safety Data
IPH2201 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 not
Slide 38: IPH43: First-in-Class Anti-MICA mAb
IPH43 FIRST-IN-CLASS ANTI-MICA MAB • MICA 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. MICA expression is upregulated by chemotherapies HeLa C. D. Tissue Positive/Total cases % Positive A. Breast Can
Slide 39: IPH43: First-in-Class Anti-MICA mAb
IPH43 FIRST-IN-CLASS ANTI-MICA MAB • Newly generated anti-MICA mAb display high affinities, are pan-alleles and can mediate direct cytotoxic effect through ADCC and/or CDC (not shown) and demonstrate in vivo efficacy ADCC Curative setting (SC model) KHYG-1-hCD16 vs. C1R-MICA*08 Page 39
Slide 40: 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 41: 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 42: 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 2.0 or 4.0 Pa
Slide 43: 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 44: Management Team
MANAGEMENT TEAM Hervé Nicolai Pierre Brailly Wagtmann Dodion PhD, PhD, MD, MBA, CEO & Co-founder Chief Scientific Chief Medical Officer Officer Immunotech SA, Beckman-Coulter Novo Nordisk A/S ARIAD, Pfizer, Novartis, Aventis Jérôme Marcel Tiollier Rozencweig, PhD, MD, Chief Development President, In
Slide 45: Bibliography
BIBLIOGRAPHY LIRILUMAB, ANTI-KIR > Kohrt et al., 2014. Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies. Blood > Vey et al., 2012. A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in CR. Blood >
Slide 46: Bibliography
BIBLIOGRAPHY IPH2201, ANTI-NKG2A > Gooden et al., 2011. HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8+ T lymphocytes. PNAS > Levy et al., 2008. HLA-E protein is overexpressed in primary human colorectal cancer. International j.oncology > Zeestraten et al., 2014. Combined
Slide 47: Bibliography
BIBLIOGRAPHY PRECLINICAL PROGRAMS 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 cytomorpholo
Slide 48: 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