Slide 1: Company Presentation 2Q 2014
COMPANY PRESENTATION 2Q 2014 Page 1
Slide 2: Forward Looking Statement
Forward Looking Statement • This document has been prepared by Innate Pharma S.A. (the “Company”) solely for the purposes of a presentation to investors concerning the Company. This document is not to be reproduced by any person, nor to be distributed. • This document contains forward-looking statem
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 First-in-class immuno- • Primary focus in immuno- modulating antibodies oncology targeting innate immunity • Potential for developments in chronic Inflammation Page
Slide 4: NK cell activation improves survival in AML patients
NK cell activation improves survival in AML patients • Following allo-transplantation, NK cells protect against tumor relapse in AML patients Effects are: • Durable NK activation • Safe • Controlled by KIR • Mediated by NK cells NK inhibition Ruggeri et al, Blood, 2007 Page 4
Slide 5: Innate Pharma's pipeline
Innate Pharma’s pipeline PROGRAM TARGET INDICATION Valid PC PI PII PIII Acute Myeloid Leukemia Lirilumab (IPH2102/BMS-986015) KIR2DL1,2,3 Solid tumors, comb. with ipilimumab licensed to Bristol-Myers Squibb Solid tumors, comb. with nivolumab IPH2201 NKG2A Cancer IPH4102 KIR3DL2 Cutaneous T-cell lymp
Slide 6: Innate Pharma positioning in immuno-oncology
Innate Pharma positioning in immuno-oncology Clinical pipeline of immunomodulating antibodies in cancer TARGET PHASE I PHASE II PHASE III MARKET Inhibitory receptors CTLA-4 AZN BMS PD-1 / Merck KGaA, AZN, BMS, Merck, PD-L1 AMP/GSK, BMS Roche, AZN KIR IPH/BMS LAG-3 BMS IMP NKG2A IPH Activating recept
Slide 7: Lirilumab
Lirilumab Page 7
Slide 8: First-in-class NK cell checkpoint inhibitor
First-in-class NK cell checkpoint inhibitor • Fully human antibody blocking NK MHC class I KIR receptor cell inhibitory receptor KIR2DL1/2/3 - (IgG4) o Blocks interaction with MHC class 1 Stressed cell NK Cell + molecules Activating ligand Activating receptor KIR signaling inhibits NK cell • Develop
Slide 9: Intergroup ALFA/Goelams EFFIKIR Phase II trial
Intergroup ALFA/Goelams EFFIKIR Phase II trial Double-blind placebo-controled randomized trial of lirilumab in AML • First randomized Phase II of lirilumab • Sponsored by Innate 1:1:1 R Lirilumab 0.1 mg/kg q 12 weeks Minimization A Intermittent full KIR occupancy N Elderly Center D CR1 1º vs 2nd AML
Slide 10: Phase I study of lirilumab in combination with nivolumab
Phase I study of lirilumab in combination with nivolumab Patients with advanced solid tumors • Dose escalation completed • Cohort expansion in various solid tumors: > Nivolumab 3mg/kg, every other weeks and lirilumab 3mg/kg, every four weeks > Patients dosed for up to two years • Participating cente
Slide 11: Phase I study of lirilumab in combination with ipilimumab
Phase I study of lirilumab in combination with ipilimumab Patients with advanced solid tumors • Regimen schedule: concurrent administration q3 weeks x 4 then q12 weeks x 4 • Dose escalation: observation period of 9 weeks after first cycle Dosage during dose escalation Dose level Total number Lirilum
Slide 12: Lirilumab enhances efficacy of rituximab
Lirilumab enhances efficacy of rituximab • KIR blockade enhances ADCC function of NK cells in vivo and in vitro Kohrt et al., Blood, 2013 Page 12
Slide 13: IPH2201, anti-NKG2A
r ya IPH2201, anti-NKG2A innate pharma Page 13
Slide 14: NKG2A: a checkpoint receptor on infiltrating NK and T cells
NKG2A: a checkpoint receptor on infiltrating NK and T cells NK cell CD8+ T cell Effector functions Effector functions + - + - NKG2D NKp46 CD94/NKG2A TCR CD94/NKG2A CD8 MIC-A ??? HLA-E HLA-A, B (C, E) HLA-E Target cell (tumor or infected cell, stressed cell in chronic inflammation) Page 14
Slide 15: Mechanism of action of IPH2201 (anti-NKG2A)
Mechanism of action of IPH2201 (anti-NKG2A) • IPH2201 blocks inhibitory signaling, enhancing immune attack on tumor cells ex vivo and in vivo Infiltrating NK and Stressed cell CD8+ T cells Anti-NKG2A Direct killing NKG2A - receptor HLA-E + + + Activating Activating receptor ligand Cytokine release P
Slide 16: Potential for development of IPH2201 in diverse tumors
Potential for development of IPH2201 in diverse types of hematological and solid tumors • HLA-E upregulated on a wide variety of tumor types; can correlate with poor prognosis Internal data Page 16
Slide 17: Phase II ready
Phase II ready • Dose-escalation safety trial conducted by Novo Nordisk A/S o 92 pts, moderate RA, low-dose MTX o IV single dose (SD, up to 10 mg/kg) and SC SD and MD (up to 4 mg/kg) o No safety issues identified, MTD not reached, no DLT • Favorable safety profile, and first-in-class target, suggest
Slide 18: IPH2201 initial development plan
IPH2201 initial 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 Additional indications to be considered: • Melanoma • Cervix • AML • Renal • Colorectal • Bladder • NSCLC
Slide 19: Portfolio of first-in-class therapeutic mAbs with diverse MOAs
Portfolio of first-in-class therapeutic mAbs with diverse MOAs Compound Ab type MOA Anti-KIR2DL1/2/3 IgG4 Activate NK cells Anti-NKG2A IgG4 Activate NK and CD8+ T cells ADCC, target tumor antigen Anti-KIR3DL2 IgG1 Rare disease Anti-TLR3 IgG4 Blocking inflammation ADCC, target tumor antigen Anti-MICA
Slide 20: Corporate information
Corporate information • Cash on hand: €37.2 million at March 31, 2014 Shareholders 11,1% • Listed on Euronext, IPO in November 2006 • Euronext Paris: FR0010331421 – IPH 10,4% • €128m raised since inception 8,8% 55,3% • Stock liquidity (in 2013) 5,9% 5,9% • 46.7m outstanding shares (48.1m diluted) 2,
Slide 21: Appendix
Appendix innate pharma
Slide 22: Appendix
Appendix Innate pharma nce 9
Slide 23: Therapeutic potential of NK cells in Acute Myeloid Leukemia
Therapeutic potential of NK cells in Acute Myeloid Leukemia MHC KIR Class I receptor • NK cell activation shown to bring clear clinical benefit in bone marrow allografts in Acute NK Cell Myeloid Leukemia patients Stressed Cell + Activating Activating > KIR-ligand incompatibility ligand receptor KIR-
Slide 24: Phase I in AML with IPH2101
Phase I in AML with IPH2101 Hybridoma anti-KIR mAb • 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 • Doses ranged from 0.0003 to 3 mg/kg – F
Slide 25: EffiKIR positioning in Acute Myeloid Leukemia
EffiKIR positioning in Acute Myeloid Leukemia Strong medical need for 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 Inducti
Slide 26: 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 26
Slide 27: NKG2A expression on tumor infiltrating lymphocytes
NKG2A expression on tumor infiltrating lymphocytes Upregulation of NKG2A on NKG2A on tumor infiltrating 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 27
Slide 28: Phase 2 trial of IPH2201 as a single agent in SCCHN
Phase 2 trial of IPH2201 as a single agent in SCCHN 2014 2015 2016 2017 H&N Phase 2 single agent Patient selection: • Stage III/IV SCCHN Optimum 2-stage Simon • Metastatic or recurrent design • HPV + and HPV - • 19 - 39 evaluable • Documented PD within 1 month of platinum- patients based chemotherap
Slide 29: Phase 2 trial of IPH2201 + cetuximab in platinum-refractory SCCHN
Phase 2 trial of IPH2201 + cetuximab in patients with platinum-refractory SCCHN 2014 2015 2016 2017 H&N Phase 2 combo cetuximab Patient selection: • Stage III/IV SCCHN • Metastatic or recurrent Optimum 2-stage Simon • Platinum Refractory : documented PD within design 1 month of platinum –based chemo
Slide 30: Phase 2 trial of IPH2201 + ibrutinib in relapsed CLL
Phase 2 trial of IPH2201+ ibrutinib in relapsed CLL 2014 2015 2016 2017 CLL Phase 2 combo ibrutinib Patient selection: Optimum 2-stage Simon • Relapsed refractory CLL design • ≥ 2 prior regimens • 10 – 29 evaluable patients • PS 0-1 • Neutro ≥ 750, platelets ≥ 50,000 Primary endpoint • CR (Internati
Slide 31: Phase 2 trial of single agent IPH2201 in ovarian cancer
Phase 2 trial of single agent IPH2201 in ovarian cancer 2014 2015 2016 2017 Ovarian Phase 2 single agent Patient selection: • Platinum resistant ovarian, peritoneal or tubal carcinoma with progression within 1-6 months of completing platinum-based • N = 25 chemotherapy • Primary endpoint: • ≤ 2 prio
Slide 32: Phase 2 trial of IPH2201 with chemotherapy in ovarian cancer
Phase 2 trial of IPH2201 combined with chemotherapy in platinum-resistant ovarian cancer 2014 2015 2016 2017 Ovarian Phase 2 combo SOC Patient selection: • Platinum-resistant disease (disease progression within <6 months of platinum therapy) • ≤ 2 prior chemotherapy regimens Optimum 2 –stage Simon •
Slide 33: Bibliography
Bibliography Lirilumab, anti-KIR o 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 o Vey et al., 2012. A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in CR. Blood o
Slide 34: Bibliography
Bibliography IPH2201, anti-NKG2A o Levy et al., 2008. HLA-E protein is overexpressed in primary human colorectal cancer. International journal of oncology o Iwaszko et al., 2011. Clinical significance of the HLA-E and CD94/NKG2 interaction. Archivum immunologiae et therapiae experimentalis o Gunturi
Slide 35: Key figures
Key figures Year ended December In thousands of euros 2013 2012 Revenue from collaboration and licensing agreements 12,469 10,377 Government financing for research expenditures 4,182 3,905 Revenue and other income 16,652 14,282 Research and development expenses (15,131) (13,417) General and administ
Slide 36: Investor relations
Investor relations Laure-Hélène Mercier Director, Investor relations investors@innate-pharma.com Tel: +33 (0)4 30 30 30 87 Fax: +33 (0)4 30 30 30 30 Page 36