Slide 1: Understanding the Potential of Lacutamab Across T Cell Lymphoma
Understanding the Potential of Lacutamab Across T Cell Lymphoma February 9, 2021 © 2020 Innate Pharma. All rights reserved. PARIS: IPH.PA NASDAQ: IPHA
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
Slide 3: Agenda
AGENDA Welcome & Introduction Mondher Mahjoubi, MD Lacutamab Overview & Development Strategy Joyson Karakunnel, MD, MSc, FACP Epidemiology & Unmet Need in CTCL & PTCL Pierluigi Porcu, MD Collaboration with LYSA for PTCL Olivier Hermine, MD, PhD Upcoming Catalysts & Concluding Remarks Joyson Karakunn
Slide 4: Speakers on today's call
Speakers on today’s call Pierluigi Porcu, MD Professor of Medical Oncology, Dermatology and Cutaneous Biology Mondher Mahjoubi, MD Director, Division of Hematologic Malignancies and Hematopoietic Chief Executive Officer Stem Cell Transplantation at Thomas Jefferson University, US Chairman of the Exe
Slide 5: A Leading Company in the Field of Innate Immunity
A Leading Company in the Field of Innate Immunity • Global, clinical-stage oncology-focused MARSEILLE FRANCE biotech company. ROCKVILLE MARYLAND • Scientific excellence in the field of innate immunity with expertise in natural killer cell biology and antibody engineering. • Focused pipeline of antib
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
Slide 7: Strong Science + Strong Partnerships = Robust Pipeline
Strong Science + Strong Partnerships = Robust Pipeline Validated Strong Track Robust Science Record of Pipeline in high-impact Collaborations with innovative publications pre-clinical and with industry and clinical assets academia 7
Slide 8: 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) Cancer antigen presentation (DCs) Lymph node Trafficking of T cells to tumors Reverse suppression 3 Ampliication of the innate immune re
Slide 9: Innate's Robust Pipeline Leveraging Expertise in Antibody Engineering & Innate Immunity
Innate’s Robust Pipeline Leveraging Expertise in Antibody Engineering & Innate Immunity Against Novel Cancer Targets 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 P
Slide 10: Lacutamab Overview & Development Strategy
Lacutamab Overview & Development Strategy Joyson Karakunnel, MD, CMO
Slide 11: Lacutamab: Lead Proprietary Asset
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 Oncology • EMA PR
Slide 12: 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
Slide 13: Phase 2 TELLOMAK Study Evaluating Lacutamab Across Subtypes of CTCL
Phase 2 TELLOMAK Study Evaluating Lacutamab Across Subtypes of CTCL Cohort SS all comers (≥ 2 lines including mogamulizumab) #1 SS N=~60 Stage 1 Stage 2 Cohort MF KIR3DL2 Expressing MF KIR3DL2 Expressing (≥ 2 prior systemic therapies) (≥ 2 prior systemic therapies) #2 MF N=21 N=29 Cohort MF KIR3DL2
Slide 14: Early Signals in KIR3DL2-Expressing MF Support Advancing Cohort 2 into Stage 2
Early Signals in KIR3DL2-Expressing MF Support Advancing Cohort 2 into Stage 2 of TELLOMAK Stage 1 Stage 2 Cohort MF KIR3DL2 Expressing MF KIR3DL2 Expressing (≥ 2 prior systemic therapies) (≥ 2 prior systemic therapies) #2 MF N=21 N=29 Cohort MF KIR3DL2 non-Expressing MF KIR3DL2 non-Expressing (≥ 2
Slide 15: Data-Driven Strategy in PTCL
Data-Driven Strategy in PTCL N O W N E X T S T E P S RELAPSE SETTING 03 FRONTLINE Highest unmet medical need; Driven by data in relapse setting two-pronged approach: to advance into earlier lines • Single agent activity (monotherapy) 02 • Combination with CHOP • Combination studies with: 1) GemOx an
Slide 16: Pierluigi Porcu, MD
Pierluigi Porcu, MD Professor of Medical Oncology, Dermatology and Cutaneous Biology Director, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation at Thomas Jefferson University, US Principal Investigator of Innate’s Phase 2 TELLOMAK clinical trial
Slide 17: T-cell Lymphomas: Epidemiology, disease spectrum, and clinical unmet need
T-cell Lymphomas Epidemiology, disease spectrum, and clinical unmet need Pierluigi Porcu, MD
Slide 18: Estimated New Cases of Leukemia, Lymphoma, and Myeloma in the US, 2019
Estimated New Cases (%) of Leukemia, Lymphoma, and Myeloma in the US, 2019 Cutaneous T-cell lymphomas ~2,000-2,500/year Figure 1 Source: Cancer Facts & Figures, 2019. American Cancer Society; 2019 Pierluigi Porcu, MD
Slide 19: WHO 2016 Classification of T-Cell Neoplasms
WHO 2016 Classification of T-Cell Neoplasms Pierluigi Porcu, MD
Slide 20: Cutaneous T-cell Lymphomas
Cutaneous T-cell Lymphomas Pierluigi Porcu, MD
Slide 21: CTCL Incidence Varies by Subtype, Subtypes Difficult to Diagnose
CTCL Incidence Varies by Subtype, Subtypes Difficult to Diagnose • CTCLs are heterogenous hematologic neoplasms of skin-homing, mature T cells • Initially skin-limited, they can involve visceral organs, lymph nodes, and blood1,2 • Annual incidence rate of CTCL ~0.5 per 100,000 people3 (~3,000/year);
Slide 22: Mycosis Fungoides: A low grade CD4+ T-cell lymphoma
Mycosis Fungoides: A low grade CD4+ T-cell lymphoma 1. A state of dynamic but stable equilibrium Normal or • Evolving (pre)malignant T-cell clone(s) Disease specific survival for Near normal • Near normal immune system early stage (IA, IB, IIA) MF Immune Competence 2. A state of dynamic and unstable
Slide 23: What is Sezary Syndrome?
What is Sezary Syndrome? Three clinical elements to Drug Overlap with MF determine response in SS Reactions PRP 1. Erythroderma (Skin) Benign Dermatoses 2. Circulating Tumor Cells (Blood) Atopic 3. Lymphadenopathy (Lymph Nodes) Dermatitis Erythroderma Blood Stage T4 Stage B2 Eosinophilia Increased I
Slide 24: Management of CTCL and Risk for Progression
Management of CTCL and Risk for Progression • MF is immunologically responsive Risk to progress to advanced disease • Multiple therapies necessary over disease course • Although FDA has approved multiple therapies, there is a high unmet need because most patients progress • Stable Disease is a meani
Slide 25: Natural Course of MF
Natural Course of MF – Indolent but progressive, lifelong poor QoL, multiple sequential therapies, not curable Mycosis Fungoides Sezary Syndrome median survival for all comers ~15 years median survival 2-3 years Early Stage MF Relapse from CR or Relapse from CR, Failure to maintain PR, Presentation
Slide 26: Six Systemic Agents are Approved for CTCL Treatment
Six Systemic Agents are Approved for CTCL Treatment Therapy MOA Approval Indication ORR% (year) Bexarotene (Targretin ®) 1, 2 Retinoid X agonist FDA/EMA Cutaneous lesions in 32% (2001) patients with CTCL refractory to ≥ 1 prior 15.8% (2017) systemic therapy Vorinostat (Zolinza ®) 3, 4 HDAC Inhibitor
Slide 27: Systemic Treatment Options in CTCL
Systemic Treatment Options in CTCL Mycosis fungoides Sézary syndrome Bexarotene, bexarotene-based 1st line ECP, Bexarotene + interferon combinations 2nd line Brentuximab / Mogamulizumab Mogamulizumab 3rd line Romidepsin / vorinostat ^ 4th line Interferon, methotrexate, gemcitabine, liposomal-doxorub
Slide 28: Peripheral T-cell Lymphomas
Peripheral T-cell Lymphomas Pierluigi Porcu, MD
Slide 29: COMPLETE Registry: Distribution of Diagnoses
COMPLETE Registry: Distribution of Diagnoses Pierluigi Porcu, MD Subtypes vary in geographic distribution and outcome
Slide 30: Progression Free Survival: Relapsed/Refractory PTCL
Progression FreeSurvival (PFS): Relapsed/RefractoryPTCL BCCA N=153 Romidepsin N=130 Brentuximab N=56 (ALCL) 3.7 months 4 months BV now approved 13.3 months in front line setting for CD30+ PTCL (US) and Brentuximab CD30+ ALCL (EU), Pralatrexate N=109 • PTCL N=21 thus no longer an Belinostat N=129 • A
Slide 31: PTCL: Current SOC
PTCL: Current “SOC” 1st line 2nd line ≥ 3rd line CD30 expressing Brentuximab CHP ~40% (mostly ALCL) Combination chemotherapy (e.g. GemOx, DHAP) Romidepsin (FDA approved) Pralatrexate (FDA approved) CD30 non-expressing Belinostat (FDA approved) CHOP-like chemo Single agent chemo (Gemcitabine) ~60% CD
Slide 32: Relapsed/Refractory PTCL: Current Treatment Overview
Relapsed/Refractory PTCL: Current Treatment Overview • Frontline therapy for PTCLs produces good response rates, including complete response rates, but fails to induce durable remission in most patients • With the exception of ALCL (Brentuximab vedotin), there is no consensus salvage therapy for pat
Slide 33: Targeting KIR3DL2 in TCL
Targeting KIR3DL2 in TCL Pierluigi Porcu, MD
Slide 34: Role of KIR3DL2 in CTCL
Role of KIR3DL2 in CTCL • KIR3DL2 is a member of the highly polymorphic family of killer-cell immunoglobulin-like receptors. • It is expressed on subsets of normal T and NK cells but widely expressed in most subtypes of T-cell lymphoma. • It is proposed as a the most sensitive diagnostic and prognos
Slide 35: KIR3DL2 expression in CTCL, according to WHO-EORTC subtype
KIR3DL2 expression in CTCL, according to WHO-EORTC subtype Sézary pt #1 Sézary pt #2 Sézary pt #3 86.5% KIR3DL2+ tumorcells 75.5% KIR3DL2+ tumor cells 77.5% KIR3DL2+ tumorcells tMF pt #1 tMF pt #2 tMF pt #3 88% KIR3DL2+ tumor cells 96% KIR3DL2+ tumor cells 83% KIR3DL2+ tumor cells INNATE PHARMA INTE
Slide 36: KIR3DL2 expression in PTCL
KIR3DL2 expression in PTCL (Innate Pharma proprietary IHC test) AITL (3/6) PTCL-NOS (7/11) ALCL (6/8) • AITL: Angio-Immunoblastic T-cell Lymphoma; • PTCL: Peripheral T-Cell Lymphoma; • ALCL: Anaplastic Large cell Lymphoma. Pierluigi Porcu, MD M. Cheminant et al, ICML 2019
Slide 37: Lacutamab: Phase I data
Lacutamab: Phase I data Pierluigi Porcu, MD
Slide 38: Phase 1 Trial Design and Key Results in SS patients
Phase 1 Trial Design and Key Results in SS patients Sézary Syndrome Subgroup (n=35) FDA Fast Track Designation granted based on these results Best Global Total 44 patients with CTCL ≥ 2 lines oftherapy Response Best change in mSWAT as compared to baseline • 25 (incl. 20 SS) in dose escalation (intra
Slide 39: Representative Patient Pictures: Patient 11-024
Representative PATIENT pictures: PATIENT 11-024 Screening Patient 11-024: • 75-year old male • Sézary Syndrome diagnosed in AUG2011 • 6 lines of previous therapies (incl. MTX, INFα, vorinostat then mogamulizumab, BEX, pembrolizumab) • Started at 3 mg/kg on 16OCT16 • Global PR since W14 (3 mg/kg) W28
Slide 40: Putting Lacutamab Phase 1 Data into Clinical Context
Putting Lacutamab Phase 1 Data into Clinical Context Recent results in MF/SS patients Mogamulizumab Vorinostat Patient population Patients who received at least one prior systemic therapy Response rate MF/SS: 28% MF/SS: 5% MF: 21% MF: 7% SS: 37% Sézary: 2% Median progression-free survival MF/Sézary:
Slide 41: Main Conclusions
Main Conclusions • SS represents an area of highest unmet medical need within CTCL • Lacutamab has promising activity with 43% Global Response highly meaningful. If data confirmed in TELLOMAK > important paradigm shift in SS patients with >2 prior systemic therapies • MF most common CTCL subtype; pa
Slide 42: Olivier Hermine, MD, PhD
Olivier Hermine, MD, PhD Professor of Hematology at the University of Paris Descartes Director, Division of Adult Hematology at Hôpital Universitaire Necker Enfants Malades Head of Lab. Cell. and mol. mechanisms of hematological disorders and therapeutic implications, INSERM U1163/Imagine Institute
Slide 43: Introducing LYSA & LYSARC
Introducing LYSA & LYSARC TOMORROW, BETTER TREATMENT FOR LYMPHOMA PATIENTS
Slide 44: Our Network
Our Network • Cooperative network of +500 lymphoma specialists • 120+ centers • 4 countries: France, Belgium, Portugal, Israel • Numerous international collaborations • Strong track record for oncology breakthroughs + Instituto Português de Oncologia of Lisbon + Sheba Medical Center of Tel Aviv LYSA
Slide 45: Our Missions
Gather lymphoma specialists Disseminate Our organized network of professionnals and knowledge on opinion leaders lymphoma Missions scientific journals, international congresses, Design research programs towards patients and clinical trial protocols at all stages of the disease 130+ from phas
Slide 46: Our Databases and Collections
30,000+ studied patients Our Databases and Collections LYSA-P Proof of concept for new projects LYSA-IM LYSA-BIO Clinical Trial Ancillary Studies Bioinformatics imaging PROPRIETARY Biostatistics biology DATABASE genomics 23,000+ … PATIENTS Data Publications clinical biological Collaborations Academi
Slide 47: A Visible Contribution to the Progress of Adult Lymphoma Therapy
A Visible Contribution to the Progress of Adult Lymphoma Therapy • Landmark phase II & III trials – benefit of rituximab in diffuse large cell lymphoma and in follicular lymphoma (former GELA group) – role of adjuvant radiotherapy in localized lymphoma, first studies with PET-CT adapted therapy • Id
Slide 48: LYSARC: Rationale for combining lacutamab with GEMOX
LYSARC The Lymphoma Academic Research Organisation Rational for combining lacutamab with GEMOX
Slide 49: Combination of Lacutamab with Gemox has synergistic anti-tumor activity in-vitro
Combination of Lacutamab with Gemox has synergistic anti-tumor activity in-vitro Increased surface KIR3DL2 expression by GEMOX Enhanced ADCC of IPH4102 by GEMOX Cheminant M et al, ICML 2019
Slide 50: Combination of Lacutamab with Gemox has synergistic anti-tumor activity in-vitro
Combination of Lacutamab with Gemox has synergistic anti-tumor activity in-vitro Lacutamab efficiently eliminates KIR3DL2+ primary ATL tumor cells by autologous NK cells ex vivo Cheminant, Bruneau, Ortonne, Gaulard et al, ICML 2019; Submitted
Slide 51: KILT: Randomized Phase 2 Clinical Trial of Lacutamab with GEMOX in r/r PTCL
KILT: Randomized Phase 2 Clinical Trial of Lacutamab in Combination with GEMOX in r/r PTCL Induction Maintenance Follow-up RESPONDERS: 1 visit RANDOMIZE 2:1 GEMOX + Lacutamab Maintained on lacutamab alone until every 3 R/R PTCL N=37 1 PRIOR LINE OF THERAPY disease progression or up to 2 years month
Slide 52: Global lacutamab overview
Global lacutamab overview Joyson Karakunnel, MD, CMO
Slide 53: 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
Slide 54: Summary & Upcoming Catalysts
Summary & Upcoming Catalysts Mondher Mahjoubi, MD, CEO
Slide 55: 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 • Deliver TELLOMAK with read- • Advancing NK cell-targeted • Strengthen financial position outs beginning in 2021 portfolio • Cash hori
Slide 56: Key Catalysts Over the Next 24 Months
Key Catalysts Over the Next 24 Months 2 0 2 1 LACUTAMAB MONALIZUMAB PRECLINICAL • Preliminary Phase 2 efficacy • Preliminary data on the • Update on NKCE platform data in MF combination of development • Start of PTCL studies monalizumab, cetuximab and durvalumab in IO-naïve patients with R/M SCCHN 2
Slide 57: Q&A
Q&A
Slide 58: Thank You
THANK YOU www.innate-pharma.com PARIS: IPH.PA NASDAQ: IPHA © 2020 Innate Pharma. All rights reserved.