Innate Pharma Sa Class A · EURONEXT:IPH
Innate Pharma Sa Class A — Merger or Acquisition (June 2017)
27 slides from Innate Pharma Sa Class A's merger presentation, June 2017
Slide 1: Anti-C5aR Acquisition: Novel Checkpoints in Immuno-Oncology
KIR2DL1,2,3 NKG2A NKP46 ANTI-C5AR KIR3DL2 ACQUISITION CD39 MICA/B CD73 JUNE 2017 NOVEL CHECKPOINTS IN IMMUNO-ONCOLOGY
Slide 2: Forward Looking Statement
FORWARD LOOKING STATEMENT This document has been prepared by Innate Pharma S.A. (the The information contained herein has not been independently “Company”) solely for the purposes of a presentation to verified. No representation, warranty or undertaking, express or investors concerning the Company.
Slide 3: Innate Pharma Acquires First-in-Class Anti-C5aR Antibody
INNATE PHARMA ACQUIRES FIRST-IN-CLASS ANTI-C5AR ANTIBODY
Slide 4: Anti-C5aR, a Novel Therapeutic Approach in Immuno-Oncology
ANTI-C5AR, A NOVEL THERAPEUTIC APPROACH IN IMMUNO-ONCOLOGY (IO) • Anti-C5aR (IPH5401) is a first-in-class therapeutic mAb targeting myeloid-derived suppressor cells (MDSC) and neutrophils in the tumor microenvironment > These cells suppress anti-tumor immune-responses > They are associated with resi
Slide 5: Strengthening of Innate Pharma's Pipeline of First-in-Class mAbs in IO
STRENGTHENING OF INNATE PHARMA’S PIPELINE OF FIRST-IN-CLASS MABS IN IO Checkpoint-inhibited T and NK cells No T or NK cells T and NK cells suppressed or excluded in tumor Inflamed Non inflamed NK cell checkpoint MDSC Bispecific antibodies lirilumab IPH5401 NK and T cell checkpoint ADCC mAb monalizum
Slide 6: Summary of the Transaction
SUMMARY OF THE TRANSACTION • Agreement granting IPH full worldwide exclusive rights to develop and commercialize a first-in-class clinical-stage anti-C5aR antibody • Upfront payment of €40M > €37.2M in new Innate shares and €2.8M in cash > The number of shares to be issued will be based on the 10 da
Slide 7: Rationale for Targeting MDSC and C5aR in Oncology
RATIONALE FOR TARGETING MDSC AND C5AR IN ONCOLOGY
Slide 8: IPH5401, a First-in-Class mAb
IPH5401, A FIRST-IN-CLASS MAB MECHANISM OF ACTION • IPH5401 is a fully human anti-C5aR blocking antibody > High affinity and high potency; no Fc-mediated depletion or agonist activity • Has potential to enhance anti-tumor immunity across a range of tumor types > MDSC-targeting has proven effectivene
Slide 9: MDSC Are Abundant in Numerous Cancers
MDSC ARE ABUNDANT IN NUMEROUS CANCERS Gentles et al. Nature Medicine 2015 Page 9
Slide 10: MDSC and Neutrophils Often Associated with a Poor Prognosis
MDSC AND NEUTROPHILS ARE OFTEN ASSOCIATED WITH A POOR PROGNOSIS Gentles et al. Nature Medicine 2015 Page 10
Slide 11: MDSC May Render Patients Refractory to Checkpoint Blockers
MDSC MAY RENDER PATIENTS REFRACTORY TO CHECKPOINT BLOCKERS Hedge et al., Clin Cancer Res 2016 Page 11
Slide 12: MDSC Promote Tumor Growth and Suppress Anti-Tumor Immune Responses
MDSC PROMOTE TUMOR GROWTH AND SUPPRESS ANTI-TUMOR IMMUNE RESPONSES • MDSC and neutrophils suppress effector T and NK cells by the production of cytokines and induction of Tregs • MDSC secrete pro-inflammatory and pro-angiogenic factors that promote tumor growth and metastasis • C5a is a potent chemo
Slide 13: Recent Data Provide Rationale for C5aR-Blockade in Oncology
RECENT DATA PROVIDE RATIONALE FOR C5AR-BLOCKADE IN ONCOLOGY • C5a and its receptor are upregulated in several types of cancer1,2 • C5aR mediates accumulation of MDSC in mouse tumors3 • M2 macrophages express high levels of C5aR and respond strongly to C5a-induced chemotaxis4 • C5aR signaling stimula
Slide 14: C5a and Its Receptor Are Upregulated in Several Types of Cancer
C5A AND ITS RECEPTOR ARE UPREGULATED IN SEVERAL TYPES OF CANCER • C5aR appears to be highly express in several cancer types with abundant MDSC 1 IHC for C5aR in colorectal and esophagus 2 Elevated levels of C5a in circulation of NSCLC patients 1 1 Hidetoshi Nitta et al., Clin Cancer Res, 2013; 2 Cor
Slide 15: C5aR KO Mice: Fewer MDSCs and Reduced Tumor Growth
C5AR KO MICE: FEWER AND LESS FUNCTIONAL MDSCs, AND REDUCED TUMOR GROWTH C5aR KO mice MDSCs from have reduced C5aR KO mice numbers of are unable to tumor suppress T cell infiltrating proliferation MDSCs MDSCs from C5aR KO mice C5aR KO mice produce have reduced reduced levels tumor growth of ROS and R
Slide 16: Human M2 Macrophages Express High Levels of C5aR
HUMAN M2 MACROPHAGES EXPRESS HIGH LEVELS OF C5AR AND RESPOND STRONGLY TO C5A-INDUCED CHEMOTAXIS 100 100 M 1 % C D 1 3 7 + N K c e lls % C D 1 3 7 + N K c e lls 80 80 M 2 60 60 40 40 M1 and M2 migrations were 20 20 performed individually and 0 0 T u m o r c e lls M IC A * 0 0 1 - + + + - + + + quanti
Slide 17: C5a Blockade Controls Lung Tumor Growth, Synergizes with Anti PD-1
C5A BLOCKADE CONTROLS THE GROWTH OF ESTABLISHED LUNG TUMORS, AND SYNERGIZES WITH ANTI PD-1 393P model: Kras driven highly aggressive lung adenocarcinoma Similar efficacy observed in a model of Lewis lung cancer Ajona D et al; Cancer Discovery 2017 Page 17
Slide 18: Conclusions
CONCLUSIONS • Tumor microenvironment and infiltration by immunosuppressive cells (e.g. MDCS) are increasingly viewed as a key tumor escape mechanism • Anti-C5aR is a novel approach for reducing infiltration and activation of MDSC > Inhibits both MDSC and suppressor neutrophils • IPH5401 is a first-i
Slide 19: Broad, Innovative and Diversified Portfolio
BROAD, INNOVATIVE AND DIVERSIFIED PORTFOLIO CLINICAL PROGRAM TARGET INDICATION STAGE OWNERSHIP Squamous cell carcinoma of the head and neck (SCCHN) Randomized Phase I/II Licensed to Lirilumab KIR2DL-1,-2,-3 Solid and hematological tumors - Multiple combinations Phase I & II trials Bristol-Myers Squi
Slide 20: Investor Relations
INVESTOR RELATIONS Laure-Hélène Mercier Chief Financial Officer investors@innate-pharma.com Tel: +33 (0)4 30 30 30 87
Slide 21: Appendix
APPENDIX
Slide 22: Bibliography: Targeting MDSC
BIBLIOGRAPHY: TARGETING MDSC • The role of myeloid cells in cancer therapies (Engblom et al. Nat. Rev. Cancer 2016) • Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells (Kim et al. PNAS 2014) • Prostate: Effective combinatorial imm
Slide 23: Bibliography: C5aR in Cancer
BIBLIOGRAPHY: C5AR IN CANCER • Complement C5a Receptor (C5aR) promotes myeloid-derived suppressor cells (MDSC) and reduces T cells (Markiewski et al Nature Immunology 2008) • C5aR ko mice exhibit reduced tumor grwoth and in mouse TC1 solid tumor model, single-agent C5aR antagonist peptide inhibited
Slide 24: C5a/C5aR Pathway in MDSCs and Cancer
C5A/C5AR PATHWAY IN MDSCs AND CANCER CD11b+ CD11b+ CD14- CD14+ CD15+ CD15- Ly6G+ Ly6G- C5aR is one of the few markers expressed on both Ly6C- Ly6C+ Neutrophils and MDSCs CD33- CD33+ C5aR+ C5aR+ Anti-C5aR Decreased trafficking of Neutrophils and MDSCs Recruitment of Neutrophils and MDSCs Influx of CD
Slide 25: C5aR Functions
C5aR FUNCTIONS Monocytes and macrophages . . Chamotaxie phag Neutrophils Ds a « phagocytosis Tt « adhesion CD11b/CD18T —- CD62Ll « Cytokine/chemokine release T ° transendothelial migration MMP9 ° TNFa, IL-1 and IL-6 T « chemotaxis © Synergy with TLR ligands and Ic « phagocytosis Tt « CR1, -3 and act
Slide 26: C5a Induces PD-L1 Expression and Cytokine Release in Monocytes
C5A INDUCES PD-L1 EXPRESSION AND CYTOKINE RELEASE IN MONOCYTES C5a induces PD-L1 C5a induces the production of immunosuppressive expression on human cytokines in human monocytes monocytes via C5aR1 but not C5aR2 Ling-Ling An et al., Sci Rep., 2016 Page 26
Slide 27: C5a Blockade Decreases Lung Cancer Growth and Metastasis
C5A BLOCKADE DECREASES LUNG CANCER GROWTH AND METASTASIS, AND SYNERGIZES WITH ANTI PD-1 393 P model: Kras driven highly aggressive lung adenocarcinoma Prevention of multiorgan metastasis Similar efficacy observed in a model of Lewis lung cancer Ajona D et al; Cancer Discovery 2017 Page 27