Slide 1: Company Presentation 4Q2014
COMPANY PRESENTATION 4Q2014
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: What's New in 2014 / What to Expect in 2015
WHAT’S NEW IN 2014 /WHAT TO EXPECT IN 2015 Lirilumab • 3 ongoing trials: single agent in AML and solid Lirilumab clinical trials tumors in combination read-out • 2 new combination trials in heme malignancies IPH2201 • Acquisition of full rights to IPH2201 IPH2201 Phase II trials • Phase II clinical
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 • 4 Phase I Bristol-Myers Squibb Multiple combinations Head and Neck, CLL, Ovarian IPH2201 NKG2A • First Ph
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 / Merck KGaA, AZN, Roche, AZN BMS/ONO, Merck PD-L1 AMP/GSK, BMS KIR IPH/BMS LAG-3 BMS IMP NKG2A IPH CD137 Pfizer, BMS Agonist antibodies B7-H3 Servier/MGNX CD40 CRU
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 HLA-C KIR NK cell Tumor cell + Anti-CTLA-4 Stimulation of T cells by NK cells Or Anti-PD-1 CTLA-4 or PD-1 T-cell Activation through CTLA-4 or PD-1-blockade Page 11
Slide 12: Lirilumab Enhances ADCC Function of NK Cells
LIRILUMAB ENHANCES ADCC FUNCTION OF NK CELLS Kohrt et al., Blood, 2013 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 Enrolment Phase I with Selected solid tumors: Nivolumab 162 close to cohort expansion MEL, NSCLC, GI, SCCHN, HC
Slide 14: Ongoing Clinical Program with Lirilumab
ONGOING CLINICAL PROGRAM WITH LIRILUMAB • 5 ongoing trials with lirilumab > 500+ 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 enrolment 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 complet
Slide 16: IPH2201
IPH2201 FIRST-IN-CLASS ANTI-NKG2A MAB
Slide 17: IPH2201 Targets Both NK and CD8 T Cells
$ ) IPH2201 TARGETS BOTH NK AND CD8 T CELLS ¢« NKG2A is a inhibitory receptor on tumor infiltrating CD8 T cells and NK cells « Many tumors overexpress NKG2A ligand suggesting a major mechanism of immune evasion Anti-NKG2A receptor ‘ligand NKG2A H 4 TCR H+ >- © Activating Activating F | HLA + NK and
Slide 18: Broad Potential for Development of IPH2201
BROAD POTENTIAL FOR DEVELOPMENT OF IPH2201 • HLA-E upregulated on a wide variety of tumor types Internal data Page 18
Slide 19: Phase II to Start in 2014
PHASE II TO START IN 2014 • Focused Phase II program > 5 studies, 3 indications, single agent and combinations > Indications with high expression of HLA-E > Potential for well defined, rapid path to registration > Rapid read out of primary endpoints (ORR, CRR) • More comprehensive results by end of
Slide 20: Development Plan
DEVELOPMENT PLAN 2014 2015 2016 2017 H&N Phase II single agent H&N Phase II combo cetuximab CLL Phase II combo ibrutinib Ovarian Phase II single agent Ovarian Phase II combo SOC Opportunities • Integrated biomarker studies • Other relevant indications and combinations (eg with checkpoint inhibitors)
Slide 21: IPH4102
IPH4102 FIRST-IN-CLASS ANTI-KIR3DL2 CYTOTOXIC MAB
Slide 22: 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 • 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 23: 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 24: Key Corporate and Financial Facts
KEY CORPORATE AND FINANCIAL FACTS
Slide 25: 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 26: Share Information
SHARE INFORMATION 10.3% • Listed on Euronext, IPO in November 2006 > Euronext Paris: FR0010331421 – IPH 10.2% > €178m raised since inception 7.9% 56.5% 7.3% • Stock liquidity (in 2014) 5.9% > 53.0m outstanding shares (54.4m diluted) 1.9% > Average daily trading volume >500,000 Bpifrance Participatio
Slide 27: Appendix
APPENDIX
Slide 28: Clinical Experience with Hybridoma Anti-KIR IPH2101: Phase I in AML
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 29: Clinical Experience with Hybridoma Anti-KIR IPH2101: Multiple Myeloma
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 30: 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 31: 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 32: 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 32
Slide 33: 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 33
Slide 34: 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 35: 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 36: Bibliography
BIBLIOGRAPHY IPH2201, anti-NKG2A > Levy et al., 2008. HLA-E protein is overexpressed in primary human colorectal cancer. International journal of oncology > Iwaszko et al., 2011. Clinical significance of the HLA-E and CD94/NKG2 interaction. Archivum immunologiae et therapiae experimentalis > Gunturi
Slide 37: Bibliography
BIBLIOGRAPHY 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 cytomorphology to evaluate blood
Slide 38: 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