COMPANY PRESENTATION 2Q 2014 Page 1 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 statements. Although the Company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to various risks and uncertainties, which could cause the Company’s actual results or financial condition to differ materially from those anticipated. Please refer to the risk factors outlined from time to time in the Company’s regulatory filings or publications. • This document contains data pertaining to the Company's potential markets and the industry and environment in which it operates. Some of these data comes from external sources that are recognized in the field or from Company’s estimates based on such sources. • The information contained herein has not been independently verified. No representation, warranty or undertaking, express or implied, is made as to, and no reliance should be placed on, the fairness, accuracy, completeness or correctness of the information or opinions contained herein. The Company is under no obligation to keep current the information contained in this presentation and any opinion expressed is subject to change without notice. The Company shall not bear any liability whatsoever for any loss arising from any use of this document or its contents or otherwise arising in connection therewith. • Please refer to the Document de Référence filed with the Autorité des marchés financiers (“AMF”) on April 7, 2014, available on the AMF’s website (www.amf-france.org) and on the Company’s website (www.innatepharma.com). Such documents may not be necessarily up to date. • This document and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares of the Company in any country. Page 2 Innate Pharma at a glance First-in-class immunomodulating antibodies targeting innate immunity • Leading scientific edge in innate immunity pharmacology • Portfolio of first-in-class immunomodulating mAbs • Primary focus in immunooncology • Potential for developments in chronic Inflammation Page 3 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 NK inhibition • Mediated by NK cells Ruggeri et al, Blood, 2007 Page 4 Innate Pharma’s pipeline PROGRAM TARGET licensed to Bristol-Myers Squibb Valid PC PI PII PIII Acute Myeloid Leukemia Lirilumab (IPH2102/BMS-986015) INDICATION KIR2DL1,2,3 Solid tumors, comb. with ipilimumab Solid tumors, comb. with nivolumab IPH2201 NKG2A Cancer IPH4102 KIR3DL2 Cutaneous T-cell lymphomas IPH33 TLR3 Inflammation / Autoimmunity IPH43 MICA Cancer Page 5 Innate Pharma positioning in immuno-oncology Clinical pipeline of immunomodulating antibodies in cancer TARGET PHASE I PHASE II PHASE III MARKET Inhibitory receptors AZN CTLA-4 PD-1 / PD-L1 Merck KGaA, AZN, AMP/GSK, BMS KIR BMS BMS, Merck, Roche, AZN IPH/BMS LAG-3 BMS NKG2A IPH IMP Activating receptors CD137 Pfizer CSF-1R AMG, LLY, Roche B7-H3 Servier/MGNX CD40 CRUK, Roche OX40 AZN GITR GITR Inc, Merck CD27 Celldex BMS Page 6 Lirilumab Page 7 First-in-class NK cell checkpoint inhibitor • Fully human antibody blocking NK cell inhibitory receptor KIR2DL1/2/3 (IgG4) o Blocks interaction with MHC class 1 molecules MHC class I KIR receptor Stressed cell NK Cell + Activating ligand Activating receptor KIR signaling inhibits NK cell • Development and commercialization rights licenced to Bristol-Myers Squibb in 2011 o $35 million upfront, up to $430 million in milestone payments, double-digit royalties Stressed cell NK Cell + KIR-blockade allows NK activation Page 8 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 Minimization Elderly CR1 Max 2 consolidations Not eligible for HST Center 1º vs 2nd AML No. consolidations Cytogenetics R A N D O M I Z E Lirilumab 0.1 mg/kg q 12 weeks Intermittent full KIR occupancy Lirilumab 1.0 mg/kg q 4 weeks Continuous full KIR occupancy Placebo q 4 weeks Treatment for 2 years Primary endpoint: Leukemia-Free Survival (Independent Review Committee) N=50 per arm (100 events) for overall α at 0.05 one-sided and power of 0.80, assuming median LFS of 12 months in the control group vs. 20 months in the treatment groups Recruitment period: 15-18 months; Maximum follow-up period: 24 months after last patient entry http://www.innate-pharma.com/sites/default/files/asco2013_tps3117.pdf Page 9 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 centers (USA): > Memorial Sloan-Kettering Cancer Center, New York, NY > Dana-Farber Cancer Institute, Boston, MA > University of Chicago Comprehensive Cancer Center, Chicago, IL > Johns Hopkins Comprehensive Cancer Center, Baltimore, MD > Providence Portland Medical Center, Portland, OR • Estimated enrollment: 162 http://www.innate-pharma.com/sites/default/files/asco2013_tps3110.pdf Page 10 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 number 1 2 3 4 5 Total Total number of patients 3‐9 3‐9 3‐9 3‐9 3‐9 15‐45 Lirilumab, mg/kg 0.1 0.3 1 3 3 Ipilimumab, mg/kg 3 3 3 3 10 • Participating centers (USA) > Memorial Sloan-Kettering Cancer Center, New York, NY > Dana-Farber Cancer Institute, Boston, MA • Cohort expansion: > Treat at the MTD or maximum > Ohio State University, Columbus, OH administered dose > Sarah Cannon Research Institute/ Tennessee Oncology, Nashville, TN • Indications: > Non-small cell lung cancer > Moffitt Cancer Center, Tampa, FL > Castrate resistant prostate cancer > Masonic Cancer Center, University of Minnesota, MN > Melanoma http://www.innate-pharma.com/sites/default/files/asco2013_tps3106.pdf Page 11 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 IPH2201, anti-NKG2A Page 13 NKG2A: a checkpoint receptor on infiltrating NK and T cells NK cell CD8+ T cell Effector functions + NKG2D NKp46 Effector functions - + TCR CD94/NKG2A 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 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 CD8+ T cells NKG2A receptor Stressed cell HLA-E - + + + Activating receptor Direct killing Anti-NKG2A Activating ligand Cytokine release Page 15 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 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 wide potential for combination therapy Page 17 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 • • Endometrium Others (ongoing investigations) Page 18 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 Anti-KIR3DL2 IgG1 ADCC, target tumor antigen Rare disease Anti-TLR3 IgG4 Blocking inflammation Anti-MICA TBD ADCC, target tumor antigen Modulating NK cells Other targets ADC technology Beyond I-O Beyond Cancer Beyond NK cells Page 19 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% 2,6% • 46.7m outstanding shares (48.1m diluted) • Average daily trading volume >500 000 Novo Nordisk A/S * BPI Groupe * • Analyst coverage: • Goldman Sachs, Leerink, Gilbert Dupont Wellington Management Company OrbiMed Fidelity Management Management Other/Autre * Shareholders represented at the Supervisory Board Page 20 Appendix Page 21 Appendix Page 22 Therapeutic potential of NK cells in Acute Myeloid Leukemia • NK cell activation shown to bring clear clinical benefit in bone marrow allografts in Acute Myeloid Leukemia patients > KIR-ligand incompatibility > Also seen in other hematological malignancies including multiple myeloma MHC Class I KIR receptor NK Cell Stressed Cell Activating ligand + Activating receptor KIR-mismatch situation • NK activation results in increase in graft-vsdisease without increase in graft-vs-host > Activated donor NK cells are active against malignant cells and not against normal cells of the host (patient) • Anti-KIR approach aims to mimic this situation with a drug Ruggeri et al, Blood, 2007, 110:433 Giebel et al., Blood, 102:814-819, 2003 (not shown) Velardi et al, Science, 2002, 295, 2009 (not shown) Page 23 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 – Full KIR saturation at doses ≥1mg/kg • Good tolerance with mild and transient adverse events. MTD not reached. Clear PK/PD relationship • Clinical outcome (2 patients from extension excluded, one in CR2 and one for early relapse within 5-days) Dose N* PFS (months) OS (months) <1 mg/kg 16 2. 3 12.6 1-3 mg/kg 16 9.5 20.0 HR (95%CI) 0.515 (0.245; 1.081) 0.490 (0.219; 1.096) P-value 0.075 0.076 Sources: Vey et al., Blood Sept. 21 and ASH 2013 poster Page 24 EffiKIR positioning in Acute Myeloid Leukemia Strong medical need for elderly patients • 5-year survival rate in elderly patients with AML is 5 to 15% Treatment paradigm Patients <60y (<50%) Patients >60y (>50%) ~ 50% • No current standard of care for elderly patients in post-induction setting Induction chemotherapy CR 65-85% • Intensive development effort in AML focused on relapsed / refractory disease • Lirilumab tested in maintenance for elderly patients ~ 50% CR ~ 50% Consolidation then transplantation Consolidation Maintenance chemotherapy EffiKIR trial TTP: ~ 2 years < 12 months Relapse Mortality (at 5-years): P <60y (70-80%) P >60y (85-95%) Page 25 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 5% 25% 44% KIR 26% 30% 12% 25% 33% 49% 2% 36% 23% 36% 10% 34% 20% NKG2A Internal data Page 26 NKG2A expression on tumor infiltrating lymphocytes Upregulation of NKG2A on NK cells inside tumors NKG2A on tumor infiltrating 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 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 • Metastatic or recurrent • HPV + and HPV • Documented PD within 1 month of platinumbased chemotherapy • < 1 regimen for recurrent or metastatic disease Optimum 2-stage Simon design • 19 - 39 evaluable patients • Primary efficacy endpoint: PFS at 4 months • PS 0-1 Regimen: • IPH2201: 10 mg/kg IV q4 weeks Page 28 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 Optimum 2-stage Simon • Platinum Refractory : documented PD within design • Metastatic or recurrent 1 month of platinum –based chemotherapy • No prior cetuximab or other EGFR therapy • PS 0-1 • 19 - 34 evaluable patients • Primary endpoint: RECIST Overall RR Regimen: • Cetuximab: 400mg/m2 IV then 250 mg/m2 IV weekly + IPH2201: 10 mg/kg IV q 4weeks • Until PD or untoward toxicity Page 29 Phase 2 trial of IPH2201+ ibrutinib in relapsed CLL 2014 2015 2016 2017 CLL Phase 2 combo ibrutinib Patient selection: • Relapsed refractory CLL • ≥ 2 prior regimens Optimum 2-stage Simon design • 10 – 29 evaluable patients • PS 0-1 • Neutro ≥ 750, platelets ≥ 50,000 Regimen: • Ibrutinib: 420 mg/d p.o. + IPH2201: 10 mg/kg IV q 4 weeks Primary endpoint • CR (International workshop on CLL; bone marrow biopsy confirmation) • Until PD or untoward toxicity Page 30 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 chemotherapy • ≤ 2 prior regimens for recurrent disease • PS 0-2 • N = 25 • Primary endpoint: PFS at 4 months Regimen: • IPH2201, 10 mg/kg IV q4 weeks up to progression or untoward toxicity Page 31 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 • ECOG performance status of 0-2 Regimen: Optimum 2 –stage Simon design • 15 – 35 evaluable patients • Primary endpoint: Overall response rate • Physician choice + IPH2201 10 mg/kg IV q4 weeks • Physician choice: Gemcitabine, topotecan or Doxil/Caelyx (Pegylated liposomal doxorubicin,PLD) • Until disease progression or untoward toxicity Page 32 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 Romagne et al., 2009. Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood o Vahlne et al., 2010. In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: maintained tolerance to normal cells even in the presence of IL-2. European journal of immunology o Moretta et al., 2008. Human NK cells: from HLA class I-specific killer Ig-like receptors to the therapy of acute leukemias. Immunological reviews o Ruggeri et al., 2002. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science IPH4102, anti-KIR3DL2 o o Bouaziz et al., 2010. Absolute CD3+ CD158k+ lymphocyte count is reliable and more sensitive than cytomorphology to evaluate blood tumour burden in Sezary syndrome. The British journal of dermatology Bagot et al., 2001. CD4(+) cutaneous T-cell lymphoma cells express the p140-killer cell immunoglobulin-like receptor. Blood IPH43, anti-MICA o Bauer et al., 1999. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science o Holdenrieder et al., 2006. Soluble MICA in malignant diseases. International journal of cancer. o Champsaur, M., and L.L. Lanier. 2010. Effect of NKG2D ligand expression on host immune responses. Immunological reviews See IPH website for direct links to bibliography Page 33 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 et al., 2005. The role of TCR stimulation and TGF-beta in controlling the expression of CD94/NKG2A receptors on CD8 T cells. European journal of immunology o Mamessier et al., 2011. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. The Journal of clinical investigation o Derre et al., 2006. Expression and release of HLA-E by melanoma cells and melanocytes: potential impact on the response of cytotoxic effector cells. J Immunol o Malmberg et al., 2002. IFN-gamma protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2Adependent mechanism. The Journal of clinical investigation o Levy et al., 2009. Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells. Innate immunity o Godal et al., 2010. NK cell killing of AML and ALL blasts by killer cell Ig-like receptor-negative NK cells after NKG2A and LIR-1 blockade. Journal of the American Society for Blood and Marrow Transplantation o Nguyen et al., 2005. NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect. Blood IPH33, anti-TLR3 o o Cavassani et al., 2008. TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. The Journal of experimental medicine Le Goffic et al., 2007. Cutting Edge: Influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells. J Immunol. See IPH website for direct links to bibliography Page 34 Key figures Year ended December In thousands of euros Revenue from collaboration and licensing agreements 2013 2012 12,469 10,377 4,182 3,905 16,652 14,282 Research and development expenses (15,131) (13,417) General and administrative expenses (4,313) (4,251) Net operating expenses (19,444) (17,668) (2,792) (3,386) (99) 185 (2,892) (3,199) Weighted average number of shares (in thousands): 38,703 37,802 Net loss per share (0.07) (0.08) Government financing for research expenditures Revenue and other income Operating income / (loss) Financial result Net income / (loss) • Cash & cash equivalents as at the end of 1Q 2014: €37.2m Page 35 Investor relations Laure-Hélène Mercier Director, Investor relations [email protected] Tel: +33 (0)4 30 30 30 87 Fax: +33 (0)4 30 30 30 30 Page 36
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