Innate Pharma Sa Class A · EURONEXT:IPH
Innate Pharma Sa Class A — Investor Day (October 2015)
44 slides from Innate Pharma Sa Class A's investor day presentation, Oct 2, 2015
Slide 1: CTCL Luncheon
CTCL LUNCHEON YOUN KIM, MD, PROF. OF DERMATOLOGY, STANFORD CANCER INSTITUTE & SCHOOL OF MEDICINE NEW YORK, OCTOBER 2, 2015 Page 1
Slide 2: Forward Looking Statement
FORWARD LOOKING STATEMENT This document has been prepared by Innate warranty or undertaking, express or implied, is Pharma S.A. (the “Company”) solely for the made as to, and no reliance should be placed on, purposes of a presentation to investors the fairness, accuracy, completeness or concerning t
Slide 3: Innate Pharma at a Glance
INNATE PHARMA AT A GLANCE Leading scientific edge Primary focus in innate immunity pharmacology in immuno-oncology Portfolio of first-in-class Partnerships with leaders in IO checkpoint inhibitors BMS and AZN Page 3
Slide 4: A Long Term Strategy
A LONG TERM STRATEGY CREATE AND RETAIN MAXIMAL VALUE IPH2201 (PII) NK Cell R&D collaboration • Global co-development and commercialization (2015) 2003 - 2009 • Initial payment: $250 million • Further milestone payments: up to $925 million • Double digit royalties on sales • Right to co-promote in Eu
Slide 5: Innate Pharma Pipeline
INNATE PHARMA PIPELINE PROGRAM TARGET INDICATIONS AND SETTING ONGOING STUDIES Lirilumab AML, single agent • Randomized Phase II (IPH2102/BMS-986015) KIR2DL1,2,3 licensed to Solid & heme tumors • 6 Phase I and II trials Bristol-Myers Squibb Multiple combinations IPH2201 Solid & heme tumors co-develop
Slide 6: Youn Kim, MD, Professor of Dermatology, Stanford Medical School
YOUN KIM, MD, PROFESSOR OF DERMATOLOGY, STANFORD MEDICAL SCHOOL Youn H. Kim, M.D., is an internationally renowned expert in cutaneous lymphomas. She serves as Director of the Multi-disciplinary Cutaneous Lymphoma Program, Director of the Residency Program in the Department of Dermatology, and Medica
Slide 7: Targeting KIR3DL2 with IPH4102 in CTCL
TARGETING KIR3DL2 WITH IPH4102 IN CTCL Youn H Kim, MD Department of Dermatology Director, Multidisciplinary Cutaneous Lymphoma Group Stanford Cancer Institute & School of Medicine Page 7
Slide 8: Disclosure Statement
DISCLOSURE STATEMENT Youn Kim, MD • Steering Committee > Eisai, Kyowa Hakko Kirin, Takeda/Millennium • Consultant or Advisory Board > Actelion, Celgene, Galderma, Soligenix, Neumedicine, Seattle Genetics, MiRagen, Horizon • Investigator > Kyowa Hakko Kirin, Merck, Takeda/Millennium, Seattle Genetics
Slide 9: First-in-Human Trial of Anti-KIR3DL2 IPH4102 in CTCL
FIRST-IN-HUMAN TRIAL OF ANTI-KIR3DL2 IPH4102 IN CTCL SEPTEMBRE 2015 Page 9
Slide 10: CTCL: A Rare Disease with High Unmet Medical Need
CTCL A RARE DISEASE WITH HIGH UNMET MEDICAL NEED Page 10
Slide 11: Cutaneous T-cell Lymphomas (CTCL)
Cutaneous T-cell Lymphomas (CTCL) CTCL is heterogeneous New WHO‐EORTC Classification group of NHL presenting primarily in the skin, of Mycosis fungoides and variants/subtypes malignant clonal T cells Sézary syndrome PC CD30+ lymphoproliferative disorders Subcutaneous panniculitis‐like T‐cell lymphom
Slide 12: Mycosis Fungoides & Sézary Syndrome
MYCOSIS FUNGOIDES & SÉZARY SYNDROME Most common of the cutaneous T-cell lymphomas • Continued rising annual incidence in US (SEER)1 > 0.96 per 100,000 • 3,000 new cases > ↑ by 2.9 per million per decade > 4% of NHLs • Median age at diagnosis is 55-65 yrs > Two-thirds present with early stage disease
Slide 13: Mycosis Fungoides Treatment of Varying Skin Manifestations
MYCOSIS FUNGOIDES TREATMENT OF VARYING SKIN MANIFESTATIONS Patch Tumor T1-2 T3 Plaque Erythroderma T1-2 T4 Page 13
Slide 14: Management of Extracutaneous Disease
MANAGEMENT OF EXTRACUTANEOUS DISEASE Blood Viscera Lymph node Page 14
Slide 15: Sézary Syndrome
Sézary syndrome- generalized erythroderma, keratoderma, severe itching; freq staph aureus infection Page 15
Slide 16: CTCL Landscape: Survival per WHO-EORTC Subtype
CTCL LANDSCAPE SURVIVAL PER WHO-EORTC SUBTYPE * Depending on TNMB stage Mycosis fungoides (MF) and Sézary syndrome (SS), its leukemic variant, are the most common CTCL subtypes. Overall survival depends in part on disease subtype. Agar et al, JCO 2010; Kempf et al, Blood 2011; Willemze, Blood 1997;
Slide 17: Survival Decreased with Advancing T Class and Clinical Stage
SURVIVAL DECREASED WITH ADVANCING T CLASS AND CLINICAL STAGE DSS UTILIZING REVISED STAGING SYSTEM Plaque worse than patch disease Agar et al. J Clin Oncol 2010;28:4730 Page 17
Slide 18: Current Clinical Management of CTCL, 2015
CURRENT CLINICAL MANAGEMENT OF CTCL, 2015 WWW.NCCN.ORG => NHL => MF/SS IA IB/IIA IIB III IV Limited Generalized Tumors Erythroderma Extracutan patch/plaque patch/plaque disease Topical steroid, retinoid (bex), NM ECP + IFN, bexarotene phototherapy, local RT, imiquimod Phototherapy + bexarotene or IF
Slide 19: Efficacy of Systemic Agents in CTCL
EFFICACY OF SYSTEMIC AGENTS IN CTCL ONLY 4 AGENTS WITH FDA APPROVAL Efficacy data for FDA approval Agent (Class) Indication Year Study N ORR DOR CTCL with Pivotal 96 34% 15 mo Romidepsin prior systemic 2009 (HDAC inhibitor) therapy Supportive 71 35% 11 mo Denileukin Tumors that 1999, diftitox Pivota
Slide 20: Immune Modulation with mAbs in CTCL
IMMUNE MODULATION WITH MABS IN CTCL Page 20
Slide 21: Drugs in Development in CTCL: Mogamulizumab
DRUGS IN DEVELOPMENT IN CTCL MOGAMULIZUMAB (ANTI-CCR4) • CCR4: trafficking receptor for systemic memory Th2 and regulatory T cells to skin and lung. • Preliminary results: > Phase I/II study in MF + SS patients (38 evaluable pts): • ORR = 36.8% (28.6% in 21 MF patients and 47.1% in 17 SS patients) •
Slide 22: Drugs in Development in CTCL: Brentuximab Vedotin
DRUGS IN DEVELOPMENT IN CTCL BRENTUXIMAB VEDOTIN (ANTI-CD30 DRUG CONJUGATE) • CD30: is expressed on activated B, T and NK cells, and activated monocytes in hematopoietic tissues. • Targeted delivery of potent tubulin disrupting drug (MMAE) • Preliminary results: > 2 Phase II studies (48 pts with CD3
Slide 23: Response to Brentuximab Vedotin in Stage IVA2 MF
51 yo F stage IVA2 MF with LCT in skin/LNs: response to brentuximab vedotin Pre-treatment 12/20/2012 Post 2 cycles 1/29/2013 Responses are not durable Page 23
Slide 24: Phase I Study of Nivolumab in Lymphoid Malignancies
Preliminary Results of a Phase I Study of Nivolumab in Patients with Relapsed or Refractory Lymphoid Malignancies Alexander M. Lesokhin! , Stephen M. Ansell’, Philippe Armand?, Emma C. Scott?, Ahmad Halwani’, Martin Gutierrez®, Michael M. Millenson’, Adam Cohen®, Stephen J. Schuster®, Daniel Lebovic
Slide 25: Study Design
Study Design ( Relapsed or ) (“Dose Escalation ) (dose Expansion \ (— Sips > Refractory HM (3mg/kg) (N=105) Primary Nivolumab Hodgkin ¢ Safety and Tolerability - No autoimmune 1img/kg>3mg/kg Lymphoma (n=23) disease Wks 1,4 then q2w Secondary - No prior organ or * Best Overall Response stem cell ¢ In
Slide 26: Best Overall Response
Best Overall Response Objective Complete Partial Response Rate, Responses, Responses, Stable Disease n (%) n(%) n (%) n(%) B-Cell Lymphoma* (n=29) 8 (28) 2 (7) 6 (21) 14 (48) Follicular Lymphoma (n=10) 4 (40) 1 (10) 3 (30) 6 (60) Diffuse Large B-Cell Tymphoma (n=11} 4 (36) 1 (9) 3 (27) 3 (27) T-Cell
Slide 27: KIR3DL2 & IPH4102 in CTCL: Introduction
KIR3DL2 & IPH4102 IN CTCL INTRODUCTION Page 27
Slide 28: KIR3DL2, Unique Therapeutic Target in CTCL
KIR3DL2, UNIQUE THERAPEUTIC TARGET IN CTCL • Inhibitory receptor, member of the Killer Immunoglobulin-like Receptor (KIR) family • In healthy individuals, there is limited expression of KIR3DL2 by normal blood cells (~25% NK cells and <15% T cells) • No KIR3DL2 expression on the FDA panel of human t
Slide 29: CTCL Landscape: KIR3DL2 Expression by WHO-EORTC Subtype
CTCL LANDSCAPE KIR3DL2 EXPRESSION BY WHO-EORTC SUBTYPE KIR3DL2 is expressed in ~65% of all CTCL, irrespectively of disease subtype. Expression is more prominent in Sézary syndrome, transformed mycosis fungoides and CD30+ LPD (ALCL subtype). Page 29
Slide 30: KIR3DL2 Expression in CTCL: Cutaneous Lesions
KIR3DL2 EXPRESSION IN CTCL CUTANEOUS LESIONS IHC staining of KIR3DL2 on skin biopsies of CTCL patients with Sézary syndrome, mycosis fungoides and CD30+ lymphoproliferative disorder (ALCL subtype) Page 30
Slide 31: KIR3DL2 Expression in CTCL: Leukemic Forms
KIR3DL2 EXPRESSION IN CTCL LEUKEMIC FORMS Correlation between KIR3DL2 and TCR-Vβ expression in flow cytometry on blood CTCL cells in Sézary syndrome patients (n = 32) 100 80 Spearman r = 0.6609 %CD4 +KIR3DL2+ p < 0.0001 60 40 20 0 0 20 40 60 80 100 %CD4 +Vbeta+ Marie-Cardine et al, Cancer Res. 2014
Slide 32: IPH4102 Has the Potential to Be a Highly Targeted CTCL Therapy
IPH4102 HAS THE POTENTIAL TO BE A HIGHLY TARGETED CTCL THERAPY • KIR3DL2 exhibits homogeneous expression on tumor cells • KIR3DL2 has very limited expression on normal cells subsets • Altogether, targeting KIR3DL2 may lead to > Improved targeting and better anti-tumoral effect > Improved safety prof
Slide 33: IPH4102 in CTCL: Non Clinical Efficacy Summary
IPH4102 IN CTCL NON CLINICAL EFFICACY SUMMARY Page 33
Slide 34: IPH4102 Key Features
IPH4102 KEY FEATURES • Selective binding to human KIR3DL2 with high affinity > No cross-reaction to other human KIRs • Humanized IgG1 designed to deplete KIR3DL2-positive tumor cells • Compelling efficacy in non clinical studies (large set of in vitro, in vivo and ex vivo models) > Main MOA include
Slide 35: IPH4102 Efficacy in Mouse IV Models
IPH4102 EFFICACY IN MOUSE IV MODELS IPH4102 improves survival in a dose-dependent manner 100 10 µg IC 0.01 µg IPH4102 80 0.1 µg IPH4102 Percent survival 1 µg IPH4102 60 10 µg IPH4102 40 20 0 0 20 30 40 50 60 Days (post cell injection) End of Study Mice: SCID (n = 8) RAJI-KIR3DL2: 5 M IV at D0 IPH410
Slide 36: IPH4102 Efficacy Ex Vivo: Autologous ADCC
IPH4102 EFFICACY EX VIVO: AUTOLOGOUS ADCC EXPERIMENTAL CONDITIONS • Fresh blood taken from Sézary Syndrome patients Lympho. Gate 103 • CD4 and NK cells separately sorted from PBMC of 4.05 0.09 the same patient (by negative selection) 102 NK cells • NK and CD4 mixed at various E/T ratios + CD56 IPH41
Slide 37: IPH4102 Efficacy Ex Vivo: Autologous ADCC Results
IPH4102 EFFICACY EX VIVO: AUTOLOGOUS ADCC EFFICACY RESULTS Patient #10 Patient #11 Patient #17 Patient #7 100 100 30 50 80 80 40 %7AAD+ CD4+ IPH4102 Sézary cells rituximab 20 % killing 60 60 30 alemtuzumab 40 40 20 10 20 20 10 0 0 0 0 E/T ratio IPH4102 as potent as alemtuzumab in ex vivo autologous
Slide 38: IPH4102-101 FIH Clinical Study Overview
IPH4102-101 FIH CLINICAL STUDY OVERVIEW Page 38
Slide 39: IPH4102-101 First-in-Human Study Design: Overview
IPH4102-101 FIRST-IN-HUMAN STUDY DESIGN OVERVIEW • First-in-Human Phase I study of IPH4102 • Dose-escalation + cohort expansion study • Dose-escalation part: > 10 dose levels of repeated administrations of IPH4102 > Modified 3+3 design with accelerated titration > First patient expected to be treate
Slide 40: IPH4102-101 First-in-Human Study Design: Overview
IPH4102-101 FIRST-IN-HUMAN STUDY DESIGN OVERVIEW • Patient population: > Relapsed/refractory (≥ 2 previous lines of systemic therapy) CTCL patients • All subtypes eligible > For MF/SS patients: clinical stage ≥ IB > KIR3DL2-positivity on skin biopsies is required for eligibility • Centrally assessed
Slide 41: IPH4102-101 First-in-Human Study Design: Objectives
IPH4102-101 FIRST-IN-HUMAN STUDY DESIGN OBJECTIVES • Primary objective: to assess safety & tolerability of increasing IV doses of single agent IPH4102 by: • characterizing the dose-limiting toxicities (DLT) and (S)AEs • identifying the MTD or Recommended Ph 2 Dose (RP2D) • Secondary objectives: > To
Slide 42: IPH4102-101 First-in-Human Study Design
IPH4102-101 FIRST-IN-HUMAN STUDY DESIGN STUDY DESIGN • Dose-escalation Part: • Cohort expansion Part: accelerated 3+3 design same dose for all: RP2D pts with KIR3DL2+ tumors pts with KIR3DL2+ tumors all CTCL subtypes eligible pre-selected CTCL subtypes Dose- level 10 3 (+3) pts Dose- level 4 Recomme
Slide 43: IPH4102-101 Participating Sites
IPH4102-101 FIRST-IN-HUMAN STUDY DESIGN PARTICIPATING SITES • Two-continent Phase I study • Clinical sites (dose-escalation part): > St Louis Hospital, Paris France (M Bagot) > UMC Leiden, the Netherlands (M Vermeer) > Guy’s and St Thomas’ Hospital, London UK (S Whittaker) > Stanford U, Stanford CA,
Slide 44: A Novel Targeted Immunotherapy for CTCL
A NOVEL TARGETED IMMUNOTHERAPY FOR CTCL • See Pr Martin Bagot presentation at EORTC cutaneous lymphoma task force meeting - Torino sept. 2015 Page 44