Innate Pharma Sa Class A · EURONEXT:IPH

Innate Pharma Sa Class A — Investor Day (June 2021)

60 slides from Innate Pharma Sa Class A's investor day presentation, Jun 23, 2021

  1. Slide 1: Virtual Investor Event

    Virtual Investor Event TELLOMAK: Lacutamab Data in Mycosis Fungoides ANKET™: Innate’s Next Generation NK Cell Engager Platform June 23, 2021 PARIS: IPH.PA NASDAQ: IPHA © 2021 Innate Pharma. All rights reserved.

  2. Slide 2: Disclaimer on Forward-Looking Information and Risk Factors

    Disclaimer on Forward-Looking Information and Risk Factors 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 co

  3. Slide 3: Speakers on today's call

    Speakers on today’s call Mondher Mahjoubi, M.D. Eric Vivier, D.V.M., Ph.D. Chief Executive Officer SVP, Chief Scientific Officer Chairman of the Executive Board Joyson Karakunnel, M.D., Martine Bagot, M.D., Ph.D M.Sc, FACP Professor and Head of the Dermatology Department at the Saint-Louis Hospital,

  4. Slide 4: Agenda

    AGENDA Welcome and Introductions Mondher Mahjoubi, M.D. Lacutamab Overview & Recent Developments Joyson Karakunnel, M.D., M.Sc, FACP TELLOMAK Study: Overview & Mycosis Fungoides Cohort Stage 1 Data Review Martine Bagot, M.D., Ph.D Q&A Session Mondher Mahjoubi, Joyson Karakunnel & Martine Bagot ANKET

  5. Slide 5: Today's event features key advancements in our portfolio

    Today’s event features key advancements in our portfolio Recent data presentations at ICML and FOCIS reinforce our strategy and development capabilities TELLOMAK: early data from stage 1 of the ANKET™: proprietary platform for developing KIR3DL2-expressing mycosis fungoides cohort next-generation mu

  6. Slide 6: Scientific Innovation Drives Our Strategy

    Scientific Innovation Drives Our Strategy We aim to harness our scientific know-how in innate immunity and antibody engineering to develop oncology products that improve the lives of patients Drive near-term Advance our Build a value with innovative R&D sustainable Lacutamab pipeline business 6

  7. Slide 7: Innate's Approach: Harnessing Innate Immunity in Cancer

    Innate’s Approach: Harnessing Innate Immunity in Cancer Choosing the right targets to leverage the body’s immune response Priming and activation (APCs and T cells) Engage NK cells 1 towards tumor Cancer antigen presentation (DCs) Lacutamab (KIR3DL2) Lymph node Trafficking of ANKETTM (NKp46) T cells

  8. Slide 8: Executing Against All Three Pillars of Our Strategy

    Executing Against All Three Pillars of Our Strategy Drive near-term Advance our Build a value with innovative R&D sustainable Lacutamab pipeline business • Proprietary ANKETTM platform • TELLOMAK Cohort 2 (KIR3DL2- driving pipeline • Monalizumab: Phase 3 trial expressing MF) advanced to • IPH6101/SA

  9. Slide 9: Our Robust Pipeline of Proprietary & Partnered Assets

    Our Robust Pipeline of Proprietary & Partnered Assets Program Target Indication Pre-Clinical Phase 1 Phase 2 Phase 3 Partner Sézary Syndrome PHASE 2 (FDA FAST TRACK/EMA PRIME DESIGNATION) – Lacutamab KIR3DL2 (IPH4102) Mycosis Fungoides PHASE 2 – Squamous Cell Carcinoma of the Head and PHASE 3 Neck M

  10. Slide 10: Lacutamab Overview & Recent Developments

    Lacutamab Overview & Recent Developments Joyson Karakunnel, M.D., CMO

  11. Slide 11: Lacutamab: Lead Proprietary Asset

    LACUTAMAB Lacutamab: Lead Proprietary Asset First-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody lacutamab • Lacutamab under development for the treatment of various forms of T-cell lymphomas (TCL) KIR3DL2 • Compelling Phase 1 data in Sézary syndrome (SS), published in Lancet Oncolog

  12. Slide 12: Pursuing Lacutamab Across T-Cell Lymphomas

    LACUTAMAB Pursuing Lacutamab Across T-Cell Lymphomas Sezary Cutaneous Syndrome T-Cell Lymphoma Fast to market approach (CTCL) Niche indication with high unmet need Mycosis Fungoides Expand potential beyond SS Explore impact of KIR3DL2 expression on clinical outcome Peripheral Multiple trials to supp

  13. Slide 13: Development Informed by Target Expression

    Development Informed by Target Expression KIR3DL2 EXPRESSION INCIDENCE Major markets (US, EU5, Japan), 2025 SEZARY SYNDROME • >90% of patients express target* ~80–200 patients1 • All tissues involved (skin, blood and lymph nodes) MYCOSIS FUNGOIDES 2,200–4,000 patients1 • ~50% of patients express tar

  14. Slide 14: TELLOMAK Phase 2 Study in Two CTCL Subtypes

    LACUTAMAB TELLOMAK Phase 2 Study in Two CTCL Subtypes Potential for Sézary syndrome cohort to serve as pivotal trial Sézary Syndrome (N~60) Mycosis Fungoides (N~90) ≥ 2 prior systemic therapies ≥ 2 prior systemic therapies Cohort #1 Cohort #2 Cohort #3 All comers, SS, must include KIR3DL2 expressing

  15. Slide 15: Initiating Data-Driven Strategy in PTCL

    LACUTAMAB Initiating Data-Driven Strategy in PTCL N O W N E X T S T E P S RELAPSED SETTING 03 FRONTLINE Highest unmet medical need; Driven by data in the relapsed two-pronged approach: setting to advance into earlier lines 02 • Monotherapy (Phase 1b study in mid- 2021) • Combination with CHOP • Comb

  16. Slide 16: Martine Bagot, M.D., Ph.D.

    Martine Bagot, M.D., Ph.D. Professor and Head of the Dermatology Department at the Saint-Louis Hospital, University of Paris, France

  17. Slide 17: Lacutamab in Patients with Mycosis Fungoides According to KIR3DL2 Expression: Early Results

    LACUTAMAB IN PATIENTS (PTS) WITH MYCOSIS FUNGOIDES (MF) ACCORDING TO KIR3DL2 EXPRESSION: EARLY RESULTS FROM THE TELLOMAK PHASE 2 TRIAL Martine Bagot 1, Youn Kim 2, Pier Luigi Zinzani 3, Stephane Dalle 4, Marie Beylot-Barry 5, Pablo L. Ortiz-Romero 6, Andrea Cambalia 7, Olivier Dereure 8, Laurent Mor

  18. Slide 18: Conflict of Interest Disclosure – Martine Bagot

    Conflict of Interest Disclosure – Martine Bagot - Employment or leadership position: N/A - Consultant or advisory role: Innate Pharma, Kyowa Kirin, Takeda, Galderma, Helsinn/Recordati - Stock ownership: N/A - Honoraria: N/A - Research funding: N/A - Other remuneration: N/A

  19. Slide 19: Background

    Background

  20. Slide 20: Lacutamab First-in-Class Anti-KIR3DL2 Humanized Antibody

    LACUTAMAB FIRST-IN-CLASS ANTI-KIR3DL2 HUMANIZED ANTIBODY Lacutamab VL IPH4102 Mycosis Sézary KIR3DL2 D0 Fungoides Syndrome KIR3DL2 ~ 50% of > 90% of D1 expression patients patients VH D2 Marie-Cardine A et al, Cancer Res 2014 Sponsor: Innate Pharma Battistella M et al, Blood 2017 Page 20

  21. Slide 21: Results of First-in-Human Phase 1 Study

    RESULTS OF FIRST-IN-HUMAN PHASE 1 STUDY GOOD SAFETY PROFILE AND HIGH ACTIVITY OF LACUTAMAB IN SÉZARY SYNDROME • Cutaneous T cell lymphoma = 44 > Sézary syndrome = 35 patients • ≥ 2 prior systemic therapies • No DLT, MTD not reached • RP2D: 750mg IV infusion • Global response: 42.9% (95%CI: 28 – 59)

  22. Slide 22: Patients and Methods

    Patients and Methods

  23. Slide 23: TELLOMAK: T-Cell Lymphoma Anti-KIR3DL2 Therapy

    TELLOMAK : T-CELL LYMPHOMA ANTI-KIR3DL2 THERAPY A Multi-cohort International Open-label Phase 2 Trial Lacutamab monotherapy 750mg (1 hour IV infusion) • weekly x 5, every 2 weeks x 10, every 4 weeks until progression or unacceptable toxicity. Cohort # 1 Sézary Syndrome ≥ 2 prior systemic therapies t

  24. Slide 24: Main Study Endpoints

    MAIN STUDY ENDPOINTS • Primary endpoint > Overall response rate (Global confirmed response) according to the international consensus criteria 1 • Disease evaluation  Skin (mSWAT), Blood (central flow cytometry), Lymph node and viscera (CT or PET/CT)  At week 5 then every 8 weeks x 1 year followed

  25. Slide 25: Key Eligibility Criteria

    KEY ELIGIBILITY CRITERIA • Mycosis fungoides cohorts > Relapsed and/or refractory stage IB, IIA, IIB, III, IV; > ECOG performance status ≤2; > KIR3DL2 ≥ 1% (Cohort 2) or <1% (Cohort 3) in at least one skin lesion based on central evaluation by immunohistochemistry (IHC); > No evidence of large cell

  26. Slide 26: Preliminary Results from Stage 1 of the MF Cohorts

    Preliminary Results from Stage 1 of the MF Cohorts

  27. Slide 27: Patient Characteristics

    PATIENT CHARACTERISTICS • Cohort 2: 17 / 21 recruited in Stage 1 (recruitment ongoing) • Cohort 3: 19 / 18 recruited in Stage 1 (recruitment completed) Cohort 2 Cohort 3 KIR3DL2 ≥ 1% KIR3DL2 < 1% (N=17) (N=19) Age in years, Median (range) 59 (33 – 76) 60 (19 – 81) - Female 6 (35%) 3 (16%) - Male 11

  28. Slide 28: Global Response and Duration

    GLOBAL RESPONSE AND DURATION MEDIAN FU = 4.8 MONTHS 4 confirmed (1CR, 3PR) & 2 not yet confirmed (uPR) global responses** 9 / 17 patients still ongoing therapy * reported after DCO date ** After DCO: the 2 uPR have been confirmed CR: complete response, PR: partial response, uPR: unconfirmed partial

  29. Slide 29: Response by Compartment Cohort 2 – KIR3DL2 ≥ 1%

    RESPONSE BY COMPARTMENT COHORT 2 – KIR3DL2 ≥ 1% Skin (N = 17) Involved at Compartment Responses baseline Skin 17 1CR, 8PR, 2uPR** Blood 7 4CR Lymph node 8 1PR Viscera 0 - ** After DCO: the 2 uPR in skin have been confirmed * reported after DCO date N: number, CR: complete response, PR: partial respo

  30. Slide 30: Response by Compartment Cohort 3 – KIR3DL2 < 1%

    RESPONSE BY COMPARTMENT COHORT 3 – KIR3DL2 < 1% Skin (N = 19) Involved at Compartment Responses baseline Skin 19 2 PR Blood 2 - Lymph node 6 - Viscera 0 - * reported after DCO date N: number, CR: complete response, PR: partial response Page 30

  31. Slide 31: Treatment Related Adverse Events Cohort 2 + 3

    TREATMENT RELATED ADVERSE EVENTS* (AT LEAST 5%) COHORT 2 + 3 (N = 36) Any grade Grade 3 / 4 Asthenia 4 (11%) 0 Nausea 4 (11%) 0 Arthralgia 2 (6%) 0 Diarrhea 2 (6%) 0 Fatigue 2 (6%) 0 AEs leading to treatment discontinuation 1 (3%) 1 (3%)^ Serious adverse events 1 (3%) 1 (3%) ^ Fatal adverse events 0

  32. Slide 32: TELLOMAK Conclusions

    TELLOMAK CONCLUSIONS • In MF patients, KIR3DL2 ≥ 1% appears to be more associated with advanced stage disease, blood and lymph node involvement in comparison to KIR3DL2 <1%. • Lacutamab shows high level of clinical response in MF patients with KIR3DL2 expression ≥ 1%. Expansion to stage 2 is underwa

  33. Slide 33: Q&A

    Q&A

  34. Slide 34: Latest Innovations to our proprietary multi-specific NKCE Platform - ANKET

    Latest Innovations to our proprietary multi- specific NKCE Platform - ANKET™ Eric Vivier, D.V.M., Ph.D.

  35. Slide 35: aTAg aNKp46 Fc

    aTAg aNKp46 Fc IL-2v Tag: tumor antigen ; Fc: antibody portion binding CD16

  36. Slide 36: ANKET: Innate's Proprietary NK Cell Engager Platform

    ANKET™: Innate’s Proprietary NK Cell Engager Platform First NK cell engager (NKCE) technology to engage activating ANKET™ receptors (NKp46 and CD16), a cytokine (IL-2 variant) and a tumor antigen in a single tetra-specific molecule Harnesses NK cell effector functions against cancer is a versatile,

  37. Slide 37: NK Cells Can Provide a Spark in the Immune Response

    NK Cells Can Provide a Spark in the Immune Response Priming & activation Trafficking of T cells (APCs and T cells) to tumors Cancer antigen presentation (DCs) Innate immune Infiltration of T cells killing of cancer into tumors cells (cytotoxicity) Release of Tumor antigens Promotion of adaptive immu

  38. Slide 38: NKp46 Expression is Conserved on Tumor-infiltrating NK Cells

    NKp46 Expression is Conserved on Tumor-infiltrating NK Cells % of NK Cells Positive for Receptors ns ns Healthy - Blood Healthy - Blood ns * ns *** *ns *** **** ns **** ns **** % of NK cells positive for receptors % of NK cells positive for receptors 100 100 Cancer - Blood Cancer - Blood Cancer - Tu

  39. Slide 39: Different NK Cell Receptors Have Different Signaling Pathways and Outcomes

    Different NK Cell Receptors Have Different Signaling Pathways and Outcomes NKG2D NKp46 CD16 IL-2Rb IL-2Rg DAP10 CD3ζ, FcRγ # Zap70/ PI3K PI3K JAK1/3 Syk NFAT NFB STAT5 • NK cell activation + • NK cell activation +++ • Proliferation +++ • cytotoxicity • cytotoxicity • cytokines and chemokines # ITAM

  40. Slide 40: Tetra-specific ANKET is the First Technology to Engage NKp46, CD16 and IL-2R

    Tetra-specific ANKET™ is the First Technology to Engage NKp46, CD16 and IL-2R in a Single Molecule NKG2D NKp46 CD16 IL-2Rb IL-2Rg DAP10 CD3ζ, FcRγ # Zap70/ PI3K PI3K JAK1/3 Syk NFAT NFB STAT5 • NK cell activation + • NK cell activation +++ • Proliferation +++ • cytotoxicity • cytotoxicity • cytokin

  41. Slide 41: Tetra-specific ANKET is the First Technology to Engage NKp46, CD16 and IL-2R

    Tetra-specific ANKET™ is the First Technology to Engage NKp46, CD16 and IL-2R in a Single Molecule NKG2D NKp46 CD16 IL-2Rb IL-2Rg DAP10 CD3ζ, FcRγ # Zap70/ PI3K PI3K JAK1/3 Syk NFAT NFB STAT5 • NK cell activation + • NK cell activation +++ • Proliferation +++ • cytotoxicity • cytotoxicity • cytokin

  42. Slide 42: IL-2v Does Not Bind to IL-2Ra

    IL-2v Does Not Bind to IL-2Ra CD25 (IL-2Ra) CD122 (IL-2Rb) 300 300 200 200 RU RU 100 100 0 0 -50 0 50 100 150 200 0 100 200 300 Time (s) Time (s) aTAg IL2 WT aTAg IL2v aTAg IL2v aNKp46 Fc aNKp46 Fc aNKp46 Fc 42

  43. Slide 43: IL-2v Promotes IL-2R Activation on NK Cells and Limits Regulatory T Cell Activation

    IL-2v Promotes IL-2R Activation on NK Cells and Limits Regulatory T Cell Activation NKCells NK cells CD4++Foxp3 CD4 Foxp3+ +Tregs Tregs CD4++CD25 CD4 CD25lowlowT TCells cells CD8+ +T TCells CD8 cells 100 100 100 100 pSTAT5 positive cells (%) 80 80 80 80 60 60 60 60 40 40 40 40 20 20 20 20 0 0 0 0 10

  44. Slide 44: Tetra-specific ANKET Provides IL-2 Signals Targeted to NK Cells

    Tetra-specific ANKET™ Provides IL-2 Signals Targeted to NK Cells NKCells NK cells CD4++Foxp3 CD4 Foxp3+ +Tregs Tregs CD4++CD25 CD4 CD25lowlowT TCells cells CD8+ +T TCells CD8 cells 100 100 100 100 pSTAT5 positive cells (%) 80 80 80 80 60 60 60 60 40 40 40 40 20 20 20 20 0 0 0 0 10 -4 10 -3 10 -2 10

  45. Slide 45: Tetra-specific ANKET Induces NK Cell Proliferation

    Tetra-specific ANKET™ Induces NK Cell Proliferation CTV* Dilution aTAg IL2v aNKp46 Fc aTAg IL2v aNKp46 Fc null aTAg aNKp46 Fc *CTV: Cell trace violet 45

  46. Slide 46: Tetra-specific ANKET Induces Cytokine Production Upon Target Engagement

    Tetra-specific ANKET™ Induces Cytokine Production Upon Target Engagement % IFN-g+ NK Cells MIP1b MFl* (on NK Cells) aTAg IL2v aNKp46 Fc aTAg IL2v aNKp46 Fc null aTAg IL2v aNKp46 Fc aTAg IL2v aNKp46 Fc MFI: Median fluorescence intensity 46

  47. Slide 47: Tetra-specific ANKET Induces Cytotoxicity Upon Tumor Recognition

    Tetra-specific ANKET™ Induces Cytotoxicity Upon Tumor Recognition Specific Lysis of Tumor Cells (%) aTAg IL2v 100 Specific lysis (%) aNKp46 Fc aTAg IL2v aNKp46 Fc null 50 aTAg IL2v aNKp46 Fc aTAg IL2v 0 aNKp46 Fc 10 -5 10 -4 10 -3 10 -2 10 -1 10 0 10 1 10 2 Concentration (nM) 47

  48. Slide 48: Tetra-specific ANKET Has Strong Anti-tumor Efficacy In Vivo

    Tetra-specific ANKET™ Has Strong Anti-tumor Efficacy In Vivo aTAg IL2v Vehicle aNKp46 Fc Vehicle 1500 1500 Tumor volume (mm3) Tumor volume (mm3) 1200 1200 900 900 600 600 300 300 40 mm3 40 mm3 0 0 0 10 20 30 40 50 0 10 20 30 40 50 Days (post cell engraftment) Days (post cell engraftment) 48

  49. Slide 49: Tetra-specific ANKET Efficacy is NKp46-dependent

    Tetra-specific ANKET™ Efficacy is NKp46-dependent aTAg IL2v aTAg IL2v aTAg IL2v Vehicle Vehicle aNKp46 Fc aNKp46 Fc null aNKp46 Fc 1500 1500 1500 1500 Tumor volume (mm3) Tumor volume (mm3) Tumor volume (mm3) Tumor volume (mm3) 1000 1000 1000 1000 500 500 500 500 0 0 0 0 0 10 20 30 40 0 10 20 30 40 0

  50. Slide 50: Tetra-specific ANKET Induces Accumulation of Activated NK Cells at the Tumor Bed

    Tetra-specific ANKET™ Induces Accumulation of Activated NK Cells at the Tumor Bed NKp46 GzmB Ncr1 (NKp46) IFN-g GzmB Ncr1 (NKp46) Ifn-g Gzmb 200 * 3 * 800 ** ** * ** norm. to GAPDH (x1000) ** ** ** Relative expression ** Vehicle 150 600 2 100 400 1 50 200 0 0 0 aTAg IL2v le b le b le b hic zuma hic

  51. Slide 51: Optimal Efficacy Requires All Arms in a Single Tetra-specific ANKET

    Optimal Efficacy Requires All Arms in a Single Tetra-specific ANKET™ aTAg IL2v aTAg IL2v + Vehicle Vehicle aNKp46 Fc aNKp46 Fc Fc null 1500 1500 1500 Tumor volume (mm3) Tumor volume (mm3) Tumor volume (mm3) 1000 1000 1000 500 500 500 0 0 0 0 10 20 30 40 0 10 20 30 40 0 10 20 30 40 Days Days Days 51

  52. Slide 52: Superiority of Tetra-specific ANKET in a Preclinical Model of Disseminated Tumors

    Superiority of Tetra-specific ANKET™ in a Preclinical Model of Disseminated Tumors aTAg IL2v aNKp46 Fc Vehicle obinutuzumab 52

  53. Slide 53: Tetra-specific ANKET are efficient and well-tolerated in NHP

    Tetra-specific ANKET™ are efficient and well-tolerated in NHP Minimal Systemic Cytokine Release and No Sign of Toxicity in Non Human Primates, Data Not Shown 100 Vehicle B cells (% of baseline) aCD20 0.05 mg/kg IL2v 0.5 mg/kg 0 aNKp46 Fc -100 -10 0 10 20 30 Days 53

  54. Slide 54: Antibody-based NK cell Engager Therapeutics

    & innate pharma Antibody-based NK cell Engager Therapeutics (Fy) = (ad) @) w ANKET™

  55. Slide 55: Concluding Remarks, Upcoming Catalysts & Long-term Vision

    Concluding Remarks, Upcoming Catalysts & Long-term Vision Mondher Mahjoubi, M.D. 55

  56. Slide 56: Developing a New Standard of Care Across KIR3DL2-Expressing T-Cell Lymphomas

    Developing a New Standard of Care Across KIR3DL2- Expressing T-Cell Lymphomas Cutaneous T-Cell Lymphoma (CTCL) Peripheral T-Cell Lymphoma (PTCL) Phase 2 TELLOMAK Trial Multi-trial Strategy Sezary Syndome Mycosis Fungoides From Relapsed to Frontline PTCL 80-200 patients 2,200-4,400 patients ~18,000 p

  57. Slide 57: Proprietary Multi-specific Platform Therapeutically Harnessing NK cells via NKp46: ANKET

    NK CELL ENGAGERS Proprietary Multi-specific Platform Therapeutically Harnessing NK cells via NKp46: ANKETTM Activation of natural adaptive anti-tumoral response • ANKET creates an entirely new class of molecules, build T cell MULTISPECIFIC from fragments of monoclonal antibodies (mAbs), to induce sy

  58. Slide 58: Summary: Driving Value Across our Business

    Summary: Driving Value Across our Business Driving near-term Progressing an Building a sustainable value with Lacutamab innovative and robust business R&D portfolio • Initiate monotherapy and • Monalizumab: Phase 3 trial • Leverage proprietary NK cell- combination PTCL studies in 2021 ongoing, $50M

  59. Slide 59: Q&A

    Q&A

  60. Slide 60: Thank You

    THANK YOU www.innate-pharma.com PARIS: IPH.PA NASDAQ: IPHA © 2021 Innate Pharma. All rights reserved.

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