AACR WRAP UP CALL NICOLAI WAGTMANN APRIL 19 TH, 2016

Transcription

1 AACR WRAP UP CALL NICOLAI WAGTMANN APRIL 19 TH, 216

2 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 March 12, 215, available on the AMF s website ( and on the Company s website ( 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

3 INNATE PHARMA PIPELINE PROGRAM TARGET INDICATION STAGE Lirilumab Licensed to Bristol-Myers Squibb KIR2DL1,2,3 Acute Myeloid Leukemia - Single agent Solid and hematological tumors - Multiple combinations Phase II 6 Phase I & II trials Monalizumab Co-development with AstraZeneca NKG2A Solid and hematological tumors - Single agent and multiple combinations 5 Phase I/II trials IPH412 KIR3DL2 Cutaneous T-cell lymphomas Phase I IPH431 MICA Cancer Research IPH52 CD39 Cancer Research Discovery CD73 Cancer Research IPH33 TLR3 Inflammation Research TECHNOLOGY NK bispecific engagers COLLABORATIONS Sanofi Antibody Drug Conjugate (ADC) Page 3

4 AACR216 HIGHLIGHTS Broad pipeline of first-in-class checkpoint antibodies Monalizumab - durvalumab combo trial supported by data showing that addition of anti-nkg2a nearly doubled the frequency of complete tumor regressions compared to anti PD-1 alone First-in-class humanized pan-specific MICA/B acts by dual mode of action, exhibiting both ADCC and countering immuno-suppression First-in-class anti-cd39 mab targeting tumor microenvironment exhibits single-agent anti-tumor activity in mouse models New CD73 antibodies have compelling characteristics, strengthening Innate s positioning in targeting the tumor microenvironment Page 4

5 INNATE PHARMA PIPELINE PROGRAM TARGET INDICATION STAGE Lirilumab Licensed to Bristol-Myers Squibb KIR2DL1,2,3 Acute Myeloid Leukemia - Single agent Solid and hematological tumors - Multiple combinations Phase II 6 Phase I & II trials Monalizumab Co-development with AstraZeneca NKG2A Solid and hematological tumors - Single agent and multiple combinations 5 Phase I/II trials IPH412 KIR3DL2 Cutaneous T-cell lymphomas Phase I IPH431 MICA Cancer Research IPH52 CD39 Cancer Research Discovery CD73 Cancer Research IPH33 TLR3 Inflammation Research TECHNOLOGY NK bispecific engagers COLLABORATIONS Sanofi Antibody Drug Conjugate (ADC) Page 5

6 MONALIZUMAB FIRST-IN-CLASS ANTI-NKG2A MAB CO-DEVELOPMENT AND COMMERCIALIZATION AGREEMENT WITH ASTRAZENECA

7 Combination MONALIZUMAB INITIAL CLINICAL DEVELOPMENT PLAN SETTING PATIENTS INDICATION STATUS LOCALIZATION Monotherapy Phase I/II 43 Head & Neck Neo-adjuvant setting Started Dec. 214 Europe Monotherapy Phase I/II 38 Ovarian cancer High grade platinum sensitive or resistant Started Sept. 215 Canada Ibrutinib Phase I/II Up to 45 Chronic Lymphocytic Leukemia Relapsed or refractory Started Oct. 215 US Cetuximab Phase I/II Up to 7 Head & Neck Relapsed or refractory Started Dec. 215 US and Europe Durvalumab (anti-pd-l1) Phase I with cohort expansion Up to 28 Solid tumors Started Feb. 216 US and Europe Page 7

8 MONALIZUMAB TARGETS NKG2A CHECKPOINT ON NK CELLS AND CD8 T CELLS NKG2A is an inhibitory receptor on tumor infiltrating CD8 T cells and NK cells NKG2A recognize HLA-E in humans and Qa-1 in mice NK cell Tumor cell CD8 T cell NK cell and T cell inhibition by NKG2A + Activation by NKG2A blockade Page 8

9 QA-1 b IS INDUCED ON A2 CELLS IN VITRO BY IFN-g AND IN VIVO AFTER ENGRAFTMENT IN MICE A Qa-1 b PD-L1 H-2K d Medium In vitro IFN-g B Ex vivo Qa1 and PD-L1 expression also upregulated on tumor-infiltrating macrophages and monocytes Page 9

10 NKG2A AND PD-1 EXPRESSION ON A2 TUMOR INFILTRATING NK AND CD8+ T CELLS IN UNTREATED MICE Spleen Tumor NK cells NKG2A - PD-1 - NKG2A - PD-1 + NKG2A + PD-1 - NKG2A + PD CD8 T cells Distribution of NKG2A and PD-1 receptors analyzed on day 22 (means of 6 mice/group) One third of tumor infiltrating PD-1+ CD8 T cells co-express NKG2A Page 1

11 T u m o r v o l u m e ( m m 3 ) ANTI-NKG2A: SINGLE-AGENT IN VIVO EFFICACY, DEPENDENT ON PRESENCE OF NK CELLS 4 3 PR: % CR: 18 % Isotype control 4 3 PR: % CR: 4 % Anti-NKG2A 4 3 PR: % CR: % Anti-NKG2A NK cell depleted Days Days Days Anti-NKG2A mab treatment induced NK cell-mediated anti-tumor efficacy in a prophylactic setting. Mice were randomized when tumor volumes 7 mm 3 (n=1-11/group) and treated 4 times (once a week) with IC, anti-nkg2a (2 µg, iv), or anti-asialo-gm1 (1 µl, ip) mabs. Tumor volume was measured twice a week. Individual tumor volumes of one experiment. Page 11

12 C D 8 + T l y m p h o c y t e s ( % ) THE FREQUENCY OF NKG2A+ CD8 T CELLS IS INCREASED IN MICE RESISTANT TO PD-1 PATHWAY BLOCKADE N K G 2 A + P D C D 8 + T c e l l s 1 5 * * * * s p l e e n * * * * t u m o r 1 * * * 5 I C A n t i - P D - 1 Mice treated with indicated mabs (2 µg, ip, 3 times every 3-4 days) after tumor engraftment were sacrificed on days 21 and 28. CD8 + T cells were characterized by flow cytometry. Means +/- SD of % NKG2A + PD-1 + CD8 + among CD8 + T cells. P<.5 (***), P<.5 (****). N=3-6. % NKG2A + NK cells among NK cells were not modified by anti-pd-1 treatment (data not shown). Page 12

13 T u m o r v o T l u m e o r ( m v o m l u 3 ) m e ( m m 3 ) T u m o r v o l u m e ( m m 3 ) T u m o r v o T l u m e o r ( m v m o l u 3 ) m e ( m m 3 ) S u r v i v a l S ( u % r ) v i v a l ( % ) A A A T u m o r v o l u m e ( m m 3 ) A T u m o r v o l u m e ( m m 3 ) COMBINED NKG2A AND PD-1 BLOCKADE INCREASES COMPLETE RESPONSE RATE AND SURVIVAL C o n t r o l 4 C o n t r o l 4 C o n t r o l 3 4 P R : 5 % 3 C R : 5 % 2 P R : 5 % 3 C R : 5 % 2 P R : 5 % 1 C R : 5 % D a y s P R : % C R : 3 7 % 2 P R : % P R : 5 % 3 C R : 3 7 % 2 C R : 2 P 5 R % : % 1 C R : 3 7 % A n t i - N K G 2 A 4 A n t i - N K G 2 A 4 A n t i - N K G 2 A 3 4 P R : 5 % 3 C R : 1 % 2 P R : 5 % 3 C R : 1 % 2 P R : 5 % 1 C R : 1 % D a y s D a y s D a y s D a y s D a y s A n t i - P D - 1 A n t i - N K G 2 A + A n t i - P D A n t i - P D - 1 C o n t r o l 4 A n t i - N K G 2 A + A n t i - P D - 1 A n t i - N K G 2 A A n t i - P D A n t i - N K G 2 A + A n t i - P D - 1 A n t i - N K G 2 A + A n t i - P D P R : 1 % C R : 6 3 % 3 2 P R : 1 % P R : 5 % 3 C R : 6 3 % 8 2 C R : P1 R %: 1 % 2 1 C R : 6 3 % D a y s D a y s D a y s D a y s * 8 6 * * 4 * * * * 6 * * 4 2 * * * * * * 4 * * * D a y s D a y s D a y s C o n t r o l A n t i - N K G 2 A A n t i - P D - 1 D a y s D a y s Mice were randomized when tumor volumes 7 mm (n=19-2 mice/group) and treated 3 times (every D a y s D a y s D a y s 3-4 days) with IC, anti-nkg2a (2 µg, iv), anti-pd-1 (2 µg, ip) or anti-nkg2a and anti-pd-1 mab. A: Pool of individual tumor volumes of two independent experiments. B: Kaplan-Meier survival. Log Rank test, P<.5 (*), P<.5 (**), P<.5 (***). A n t i - P D - 1 A n t i - N K G 2 A + A n t i - P D - 1 B B B B S u r v i v a l ( % ) S u r v i v a l ( % ) 2 C o n t r o l A n t i - N K G 2 A C o n t r o l A n t i - P D - 1 A n t i - N K G 2 A C o n t r o l A n t i - N K G 2 A + A n t i - P D - 1 A n t i - P D - 1 A n t i - N K G 2 A 1 A n t i - N K G 2 A + A n t i - P D - 1 A n t i - P D A n t i - N K G 2 A + A n t i - P D - 1 * * * * * * m 3 ) Page 13

14 CONCLUSIONS: IPH221 Preclinical mouse model presented at AACR strongly support the combination trial of monalizumab and durvalumab: > NKG2A ligand was not expressed on A2 cells at baseline, but induced on subcutaneous solid tumor cells similar to HLA-E overexpression on tumors vs normal cells in humans > NKG2A receptor expressed on over 5% of NK cells and induced on tumorinfiltrated CD8 T cells, particularly in mice resistant to anti-pd1 > Single-agent anti-nkg2a delayed tumor growth > Treatment with combination of NKG2A and PD-1 checkpoint inhibitors resulted in significantly enhanced anti-tumor responses. Nearly twice as many mice achieved complete tumor cell regression compared to treatment with PD-1 alone > Hence, NKG2A pathway may be a significant factor in adaptive resistance to PD-1 pathway blockade Page 14

15 INNATE PHARMA PIPELINE PROGRAM TARGET INDICATION STAGE Lirilumab Licensed to Bristol-Myers Squibb KIR2DL1,2,3 Acute Myeloid Leukemia - Single agent Solid and hematological tumors - Multiple combinations Phase II 6 Phase I & II trials Monalizumab Co-development with AstraZeneca NKG2A Solid and hematological tumors - Single agent and multiple combinations 5 Phase I/II trials IPH412 KIR3DL2 Cutaneous T-cell lymphomas Phase I IPH431 MICA Cancer Research IPH52 CD39 Cancer Research Discovery CD73 Cancer Research IPH33 TLR3 Inflammation Research TECHNOLOGY NK bispecific engagers COLLABORATIONS Sanofi Antibody Drug Conjugate (ADC) Page 15

16 IPH431: FIRST-IN-CLASS ANTI-MICA/B ANTIBODY MICA and MICB are polymorphic molecules often expressed on transformed and stressed cells MICA/B are ligands for NKG2D receptors on NK cells and CD8+ T cells. Kidney carcinoma CRC Endometrium Tumor localization Positive Cases (n=) Kidney 1% (2) Large intestine/sigmoid colon 1% (2) Endometrium 1% (1) Thyroid Gland Melanoma (lung metastasis) HCC Thyroid Gland 1% (1) Metastatic melanoma 9% (1) Liver 85% (2) Breast (TMA) 82% (28) Melanoma 71% (7) Lung (TMA) 62% (29) Chronic exposure to MICA/B down-regulates NKG2D receptors MICA/B can also be expressed on immunosuppressive macrophages Page 16

17 DUAL MECHANISM OF ACTION OF IPH431 PRESENTED AT AACR NK cell Tumor cell CD8 T cell Macrophage NK and T cell inhibition by chronic exposure to MICA/B + Dual mechanism of action: tumor antigen targeting and immunomodulation Page 17

18 IPH43: POTENT ADCC BY RESTING PRIMARY HUMAN NK CELLS A549 Raji-MICA* Binding % S p e c ific L y s is % S p e c ific L y s is M F I M F I Lysis A b. [µ g /m L ] A b. [µ g /m L ] IPH431 Isotype control Rituximab Cetuximab PBMC from healthy donors E/T = 2/1 Page 18

19 % C D N K c e lls % C D N K c e lls IPH431 OVERCOMES M2 MACROPHAGE-MEDIATED SUPPRESSION OF NK CELL ACTIVITY Isotype control IPH T u m o r c e lls M IC A * 1 M 1 m a c ro p h a g e s M 2 m a c ro p h a g e s Autologous macrophages and NK cells from healthy donors Page 19

20 P r o s ta te W e ig h t (g ) IPH43-moIgG2a CURES TRAMP-MICB MICE FROM PROSTATE CANCER Prostate weight (g) P= Isotype control IPH43-moIgG2a IPH43-moIgG2a is mousified IPH431 TRAMP/MICB mice described in Liu et al. In this model, male mice spontaneously develop prostate tumors expressing human MICB around 2 weeks of age Injections of mab i.v., twice a week starting from week 22 up to sacrifice at week 29 Page 2

21 IPH43-moIgG2a CURES TRAMP-MICB MICE FROM PROSTATE CANCER, RESTORING HISTOLOGY OF PROSTATE GLAND AND INDUCING NK CELL INFILTRATION Histology Isotype control (n=8) IPH43-moIgG2a (n=9) Normal/cured /8 4/9 (E) Well differentiated 5/8 (C) No NK infiltration 5/9 Localized or stabilized tumor (F) Poorly differentiated 3/8 (D) /9 NK infiltration IPH43-moIgG2a Isotype Control C. D. E. F. Page 21

22 CONCLUSIONS: IPH431 IPH431 is a humanized first-in-class pan allotype-specific anti-mica/b antibody which : > Efficiently mediates direct killing of tumor cells by ADCC > Overcomes suppressor macrophage-induced inhibition of NK cells > Inhibits MICA/B-induced NKG2D down-modulation > Demonstrates in vivo tumor efficacy in immuno-deficient mice > Mousified IPH43 cured TRAMP-MICB mice of prostate cancer Dual mechanism of action: Tumor antigen targeting and immunomodulation IND-enabling studies to start in 216 Page 22

23 INNATE PHARMA PIPELINE PROGRAM TARGET INDICATION STAGE Lirilumab Licensed to Bristol-Myers Squibb KIR2DL1,2,3 Acute Myeloid Leukemia - Single agent Solid and hematological tumors - Multiple combinations Phase II 6 Phase I & II trials Monalizumab Co-development with AstraZeneca NKG2A Solid and hematological tumors - Single agent and multiple combinations 5 Phase I/II trials IPH412 KIR3DL2 Cutaneous T-cell lymphomas Phase I IPH431 MICA Cancer Research IPH52 CD39 Cancer Research Discovery CD73 Cancer Research IPH33 TLR3 Inflammation Research TECHNOLOGY NK bispecific engagers COLLABORATIONS Sanofi Antibody Drug Conjugate (ADC) Page 23

24 THE ADENOSINE PATHWAY: ANTI-CD39 & ANTI-CD73 TARGETING THE TUMOR MICROENVIRONMENT T cell Other immune cell Tumor spreading NK cell Anti-CD39 Anti-CD39 Anti-CD73 Dendritic cell CD8 or CD4 T cell Tumor depletion CD39 and CD73 are enzymes expressed on regulatory T cells, immune cells and tumor cells > They promote immunosuppression by degrading adenosine triphosphate (ATP) into adenosine ATP : adenosine triphosphate AMP : adenosine monophosphate Page 24

25 IPH52: NOVEL, POTENT ANTI-CD39 ANTIBODY CD39 is expressed in several human cancers, including head & neck, lung, cervical, esophageal, sarcoma, liver, kidney, pancreatic, thyroid, endometrial tumors, as well as in lymphoma and melanoma Head & neck Squamous Cell Carcinoma Cervix Squamous cell carcinoma Liver Hepatocellular liver K Pancreas Adenocarcinoma Soft tissue Mucinous liposarcoma Lung AdenoK Esophagus Adenocarcinoma Kidney Clear Cell Carcinoma Thyroid Papillary carcinoma Uterus Endometrioid AdK IPH52 is a humanized anti-cd39 mab > Aims at preventing production of immunosuppressive Ado and promoting the accumulation of ATP in the tumor microenvironment > May stimulate anti-tumor immunity across a wide range of tumors Page 25

26 T u m o r v o lu m e (m m 3 ) P e r c e n t s u r v iv a l IPH52: NOVEL, POTENT ANTI-CD39 ANTIBODY VALIDATED IN PRECLINICAL MODELS IPH52 displays single agent activity Humanized mab inhibits tumor growth in xenogeneic tumor model T u m o r g r o w t h S u r v iv a l * * * * : p < D a y s d a y s H u a C D 3 9 H u IC Page 26

27 A M P (µ M ) HUMANIZED MAB INHIBITS CD39 ENZYME ACTIVITY IN MELANOMA TUMOR BIOPSIES H u m a n M e la n o m a B io p s ie s.8.6 P a tie n t1 P a tie n t2 P a tie n t B io p s y A T P B io p s y + A T P + H u IC + H u a C D 3 9 Efficacy of Hu acd39 to inhibit ATPase activity was evaluated on tumor biopsies, collected from 3 patients with metastatic melanoma, digested at 37 C with Collagenase and DNAse. Cells were further incubated with ATP at 4 C and AMP generated was quantified by Maldi Tof-MS. Page 27

28 POTENTIAL FOR COMBINATION WITH CANCER TREATMENTS CD39 disruption drives antitumor immune responses, either alone or in combination with PD-1 checkpoint blockers, ADCC antibodies and immunogenic chemotherapy, suggesting broad development potential Treatment with anti-pd1 and oxaliplatin in CD39 KO mice leads to 86% CR Tumor growth Survival WT mice CD39ko mice Page 28

29 CONCLUSIONS: IPH52 First-in-class humanized anti-cd39 mab with high affinity and specificity for CD39 blocks ATPase activity in vitro, both on tumor cells and immune cells In vivo, humanized anti-cd39 mab significantly inhibits CD39/CD73 positive tumor growth Broad development potential suggested by experiments in CD39 knock-out mice, including combination therapy with chemotherapy, ADCC-antibodies and/or immune checkpoint inhibitors IPH52 is currently in lead optimization Page 29

30 INNATE PHARMA PIPELINE PROGRAM TARGET INDICATION STAGE Lirilumab Licensed to Bristol-Myers Squibb KIR2DL1,2,3 Acute Myeloid Leukemia - Single agent Solid and hematological tumors - Multiple combinations Phase II 6 Phase I & II trials Monalizumab Co-development with AstraZeneca NKG2A Solid and hematological tumors - Single agent and multiple combinations 5 Phase I/II trials IPH412 KIR3DL2 Cutaneous T-cell lymphomas Phase I IPH431 MICA Cancer Research IPH52 CD39 Cancer Research Discovery CD73 Cancer Research IPH33 TLR3 Inflammation Research TECHNOLOGY NK bispecific engagers COLLABORATIONS Sanofi Antibody Drug Conjugate (ADC) Page 3

31 ANTI-CD73: NEW CHECKPOINT INHIBITOR PROGRAM TARGETING THE TUMOR MICROENVIRONMENT T cell Other immune cell Tumor spreading NK cell Anti-CD39 Anti-CD39 Anti-CD73 Dendritic cell CD8 or CD4 T cell Tumor depletion Targeting CD73 may block tumor cell metastasis by reducing the generation of immunosuppressive adenosine A panel of antibodies were discovered that inhibit CD73 function by different mechanisms, including the direct blocking of CD73 enzymatic activity or the down-modulation of membrane CD73 expression ATP : adenosine triphosphate AMP : adenosine monophosphate Page 31

32 M F I (x 1 5 ) M F I (x 1 5 ) M F I M F I ANTI-CD73 ANTIBODIES BIND WITH HIGH AFFINITY TO HUMAN AND CYNOMOLGUS CD73 MOLECULES A 4 C H O -h u C D C H O -c y n o C D C H O -m o C D 7 3 C m A b (n M ) m A b (n M ) m A b (n M ) B M D A -M B C y n o m -K m A b 1 m A b 2 m A b 3 m A b 4 T Y 2 3 C o n tro l KD (nm) Ka (1/Ms) Kd (1/s) mab E5 9.36E-5 mab E5 1.6E-4 mab E4 7.41E-5 mab E4 2.13E-4 m A b (n M ) m A b (n M ) Binding of anti-cd73 mabs was evaluated by flow cytometry A: on human, cynomolgus and mouse CD73- expressing CHO cell lines and B: on human (MDA-MB-231) and cynomolgus (Cynom-K1) cell lines that endogenously express CD73. C: Affinity of anti-cd73 mabs was measured by SPR. Page 32

33 P h o s p h a t e (% o f c e lls a lo n e ) P h o s p h a t e (% o f c e lls a lo n e ) P h o s p h a t e (% o f c e lls a lo n e ) MAB1 POTENTLY INHIBITS CELLULAR CD73 ENZYME ACTIVITY WITHOUT HOOK EFFECT A R e c o m b in a n t C D 7 3 B C e llu la r C D 7 3 a c tiv ity d o w n -m o d u la tio n E n z y m e A c tiv ity (% ) S to ic h io m e tric c o n d itio n s C D 7 3 e x p r e s s io n (% o f T ) m A b 1 m A b 2 m A b 3 m A b 4 C o n tro l C m A b (n M ) C e llu la r C D 7 3 a c tiv it y T im e (m in ) M D A -M B N C I-H A m A b (n M ) m A b (n M ) m A b (n M ) Recombinant CD73 was incubated with anti-cd73 mabs then with AMP (125 µm) and ATP (12.5 µm). A: AMP degradation was indirectly measured with Cell Titer Glo reagent. B: CD73 expression after MDA-MB-231 incubation with anti-cd73 mabs at 37 C was revealed by flow cytometry with non-competing anti-cd73 mabs. C: Human tumor cell lines were incubated with anti-cd73 mabs then with AMP (1 µm). Resulting phosphate was measured in the supernatant. Page 33

34 P r o lif (% o f c o n tro l) ANTI-CD73 ANTIBODIES EFFICIENTLY REVERSE AMP-MEDIATED T CELL SUPPRESSION Activated + AMP + mab1 Activated + AMP Activated Resting C T V o n to ta l T c e lls (M F I) C D 4 + T c e lls m A b (n M ) P r o lif (% o f c o n tro l) C D 8 + T c e lls m A b (n M ) m A b 1 m A b 2 m A b 3 m A b 4 C o n tro l Cell Trace Violet (CTV)-labelled lymphocytes were incubated with anti-cd73 mabs, anti-cd3/cd28- coated beads and AMP (8µM). Cell division was followed by flow cytometry. Page 34

35 CONCLUSIONS: CD73 We have discovered new original anti-cd73 checkpoint antibodies that block CD73 enzymatic activity and/or induce CD73 down-modulation The 4 mabs efficiently reverse AMP-dependent T cell suppression in vitro The mab that most potently inhibits CD73-mediated immune suppression (Ab1) is a strong blocker of CD73 enzyme activity The 4 mabs have distinct epitopes all located on the apex of the N-terminal domain of CD73 Antibodies displaying the most interesting features were humanized and further evaluation of their activity is ongoing Page 35

36 CONCLUSIONS Broad pipeline of first-in-class checkpoint antibodies Monalizumab - durvalumab combo trial supported by data showing that addition of anti-nkg2a nearly doubled the frequency of complete tumor regressions compared to anti PD-1 alone First-in-class humanized pan-specific MICA/B acts by dual mode of action, exhibiting both ADCC and countering immuno-suppression First-in-class anti-cd39 mab targeting tumor microenvironment exhibits single-agent anti-tumor activity in mouse models New CD73 antibodies have compelling characteristics, strengthening Innate s positioning in targeting the tumor microenvironment Page 36

37 OUR RESEARCH AMBITIONS Strengthening our preclinical pipeline Growing capabilities Expanding into tumor microenvironment Harnessing our innate immunity focus and expertise Page 37

38 WHERE TO SEE US IN Q2 CIMT: Mechanisms of Efficacy in Cancer Immunotherapy Mainz - Germany May 1, 216 to May 12, 216 Innate Pharma Research Day New York, USA May 16, 216 ASCO Annual Meeting 216 Chicago, USA June 3, 216 to June 7, 216 Citi Swiss Healthcare Investor Day Zurich, Switzerland May 19, 216 Goldman Sachs 37th Annual Global Healthcare Conference Rancho Palos Verdes, USA June 7 to June 9, 216 Bryan Garnier 1st Oncology Day Paris, France June 17, 216 Société Générale CIB Healthcare & Biotechnology Conference Paris, France June 28, 216 For more events, visit our website or and our booth #264 at AACR meeting Page 38