COMPANY PRESENTATION

COMPANY PRESENTATION
2Q 2014
Page 1
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 April 7,
2014, available on the AMF’s website (www.amf-france.org) and on the Company’s website (www.innatepharma.com). 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
Innate Pharma at a glance
First-in-class immunomodulating antibodies
targeting innate immunity
•
Leading scientific edge in
innate immunity pharmacology
•
Portfolio of first-in-class
immunomodulating mAbs
•
Primary focus in immunooncology
•
Potential for developments in
chronic Inflammation
Page 3
NK cell activation improves survival in AML patients
• Following allo-transplantation, NK cells protect against tumor relapse in
AML patients
Effects are:
• Durable
NK activation
• Safe
• Controlled by KIR
NK inhibition
• Mediated by NK cells
Ruggeri et al, Blood, 2007
Page 4
Innate Pharma’s pipeline
PROGRAM
TARGET
licensed to
Bristol-Myers Squibb
Valid
PC
PI
PII
PIII
Acute Myeloid Leukemia
Lirilumab
(IPH2102/BMS-986015)
INDICATION
KIR2DL1,2,3
Solid tumors, comb. with ipilimumab
Solid tumors, comb. with nivolumab
IPH2201
NKG2A
Cancer
IPH4102
KIR3DL2
Cutaneous T-cell lymphomas
IPH33
TLR3
Inflammation / Autoimmunity
IPH43
MICA
Cancer
Page 5
Innate Pharma positioning in immuno-oncology
Clinical pipeline of immunomodulating antibodies in cancer
TARGET
PHASE I
PHASE II
PHASE III
MARKET
Inhibitory receptors
AZN
CTLA-4
PD-1 /
PD-L1
Merck KGaA, AZN,
AMP/GSK, BMS
KIR
BMS
BMS, Merck,
Roche, AZN
IPH/BMS
LAG-3
BMS
NKG2A
IPH
IMP
Activating receptors
CD137
Pfizer
CSF-1R
AMG, LLY, Roche
B7-H3
Servier/MGNX
CD40
CRUK, Roche
OX40
AZN
GITR
GITR Inc, Merck
CD27
Celldex
BMS
Page 6
Lirilumab
Page 7
First-in-class NK cell checkpoint inhibitor
• Fully human antibody blocking NK
cell inhibitory receptor KIR2DL1/2/3
(IgG4)
o Blocks interaction with MHC class 1
molecules
MHC class I
KIR receptor
Stressed cell
NK Cell
+
Activating ligand
Activating receptor
KIR signaling inhibits NK cell
• Development and commercialization
rights licenced to Bristol-Myers
Squibb in 2011
o $35 million upfront, up to $430
million in milestone payments,
double-digit royalties
Stressed cell
NK Cell
+
KIR-blockade allows NK activation
Page 8
Intergroup ALFA/Goelams EFFIKIR Phase II trial
Double-blind placebo-controled randomized trial of lirilumab in AML
• First randomized Phase II of lirilumab
• Sponsored by Innate
1:1:1
Minimization
Elderly
CR1
Max 2 consolidations
Not eligible for HST
Center
1º vs 2nd AML
No. consolidations
Cytogenetics
R
A
N
D
O
M
I
Z
E
Lirilumab 0.1 mg/kg q 12 weeks
Intermittent full KIR occupancy
Lirilumab 1.0 mg/kg q 4 weeks
Continuous full KIR occupancy
Placebo q 4 weeks
Treatment for 2 years
Primary endpoint: Leukemia-Free Survival (Independent Review Committee)
N=50 per arm (100 events) for overall α at 0.05 one-sided and power of 0.80, assuming median LFS of
12 months in the control group vs. 20 months in the treatment groups
Recruitment period: 15-18 months; Maximum follow-up period: 24 months after last patient entry
http://www.innate-pharma.com/sites/default/files/asco2013_tps3117.pdf
Page 9
Phase I study of lirilumab in combination with nivolumab
Patients with advanced solid tumors
• Dose escalation completed
• Cohort expansion in various solid tumors:
> Nivolumab 3mg/kg, every other weeks and lirilumab 3mg/kg, every four weeks
> Patients dosed for up to two years
• Participating centers (USA):
> Memorial Sloan-Kettering Cancer Center, New York, NY
> Dana-Farber Cancer Institute, Boston, MA
> University of Chicago Comprehensive Cancer Center, Chicago, IL
> Johns Hopkins Comprehensive Cancer Center, Baltimore, MD
> Providence Portland Medical Center, Portland, OR
• Estimated enrollment: 162
http://www.innate-pharma.com/sites/default/files/asco2013_tps3110.pdf Page 10
Phase I study of lirilumab in combination with ipilimumab
Patients with advanced solid tumors
• Regimen schedule: concurrent administration q3 weeks x 4 then q12 weeks x 4
• Dose escalation: observation period of 9 weeks after first cycle
Dosage during dose escalation
Dose level
number
1
2
3
4
5
Total
Total number
of patients
3‐9
3‐9
3‐9
3‐9
3‐9
15‐45
Lirilumab,
mg/kg 0.1
0.3
1
3
3
Ipilimumab,
mg/kg 3
3
3
3
10
• Participating centers (USA)
> Memorial Sloan-Kettering Cancer Center,
New York, NY
> Dana-Farber Cancer Institute, Boston, MA
• Cohort expansion:
> Treat at the MTD or maximum
> Ohio State University, Columbus, OH
administered dose
> Sarah Cannon Research Institute/
Tennessee Oncology, Nashville, TN
• Indications:
> Non-small cell lung cancer
> Moffitt Cancer Center, Tampa, FL
> Castrate resistant prostate cancer
> Masonic Cancer Center, University of
Minnesota, MN
> Melanoma
http://www.innate-pharma.com/sites/default/files/asco2013_tps3106.pdf Page 11
Lirilumab enhances efficacy of rituximab
• KIR blockade enhances ADCC function of NK cells in vivo and in vitro
Kohrt et al., Blood, 2013
Page 12
IPH2201, anti-NKG2A
Page 13
NKG2A: a checkpoint receptor on infiltrating NK and T cells
NK cell
CD8+ T cell
Effector functions
+
NKG2D NKp46
Effector functions
-
+
TCR
CD94/NKG2A
CD94/NKG2A
CD8
MIC-A ???
HLA-E
HLA-A, B (C, E)
HLA-E
Target cell
(tumor or infected cell, stressed cell in chronic inflammation)
Page 14
Mechanism of action of IPH2201 (anti-NKG2A)
•
IPH2201 blocks inhibitory signaling, enhancing immune attack on tumor
cells ex vivo and in vivo
Infiltrating NK and
CD8+ T cells
NKG2A
receptor
Stressed cell
HLA-E
-
+
+
+
Activating
receptor
Direct killing
Anti-NKG2A
Activating
ligand
Cytokine release
Page 15
Potential for development of IPH2201 in diverse types of
hematological and solid tumors
•
HLA-E upregulated on a wide variety of tumor types; can correlate with
poor prognosis
Internal data
Page 16
Phase II ready
• Dose-escalation safety trial conducted by Novo Nordisk A/S
o
92 pts, moderate RA, low-dose MTX
o
IV single dose (SD, up to 10 mg/kg) and SC SD and MD (up to 4
mg/kg)
o
No safety issues identified, MTD not reached, no DLT
• Favorable safety profile, and first-in-class target, suggest wide potential
for combination therapy
Page 17
IPH2201 initial development plan
2014
2015
2016
2017
H&N Phase II single agent
H&N Phase II combo cetuximab
CLL Phase II combo ibrutinib
Ovarian Phase II single agent
Ovarian Phase II combo SOC
Additional indications to be considered:
• Melanoma
• Cervix
•
AML
•
Renal
•
Colorectal
•
Bladder
•
NSCLC
•
•
Endometrium
Others (ongoing
investigations)
Page 18
Portfolio of first-in-class therapeutic mAbs with diverse MOAs
Compound
Ab type
MOA
Anti-KIR2DL1/2/3
IgG4
Activate NK cells
Anti-NKG2A
IgG4
Activate NK and CD8+ T cells
Anti-KIR3DL2
IgG1
ADCC, target tumor antigen
Rare disease
Anti-TLR3
IgG4
Blocking inflammation
Anti-MICA
TBD
ADCC, target tumor antigen
Modulating NK cells
Other targets
ADC technology
Beyond I-O
Beyond Cancer
Beyond NK cells
Page 19
Corporate information
• Cash on hand: €37.2 million at March 31, 2014
Shareholders
11,1%
• Listed on Euronext, IPO in November 2006
• Euronext Paris: FR0010331421 – IPH
10,4%
• €128m raised since inception
8,8%
55,3%
• Stock liquidity (in 2013)
5,9%
5,9%
2,6%
• 46.7m outstanding shares (48.1m diluted)
• Average daily trading volume >500 000
Novo Nordisk A/S *
BPI Groupe *
• Analyst coverage:
• Goldman Sachs, Leerink, Gilbert Dupont
Wellington Management Company
OrbiMed
Fidelity Management
Management
Other/Autre
* Shareholders represented at the
Supervisory Board
Page 20
Appendix
Page 21
Appendix
Page 22
Therapeutic potential of NK cells in Acute Myeloid Leukemia
• NK cell activation shown to bring clear clinical
benefit in bone marrow allografts in Acute
Myeloid Leukemia patients
> KIR-ligand incompatibility
> Also seen in other hematological malignancies
including multiple myeloma
MHC
Class I
KIR
receptor
NK Cell
Stressed
Cell
Activating
ligand
+
Activating
receptor
KIR-mismatch situation
• NK activation results in increase in graft-vsdisease without increase in graft-vs-host
> Activated donor NK cells are active against
malignant cells and not against normal cells of
the host (patient)
• Anti-KIR approach aims to mimic this
situation with a drug
Ruggeri et al, Blood, 2007, 110:433
Giebel et al., Blood, 102:814-819, 2003 (not shown)
Velardi et al, Science, 2002, 295, 2009 (not shown)
Page 23
Phase I in AML with IPH2101
Hybridoma anti-KIR mAb
• Elderly AML patients in complete remission after induction and consolidation treatment maintenance setting
• Phase I dose-escalation including 23 patients in first CR, and extension including 12
patients
• Doses ranged from 0.0003 to 3 mg/kg – Full KIR saturation at doses ≥1mg/kg
• Good tolerance with mild and transient adverse events. MTD not reached. Clear PK/PD
relationship
• Clinical outcome (2 patients from extension excluded, one in CR2 and one for early
relapse within 5-days)
Dose
N*
PFS (months)
OS (months)
<1 mg/kg
16
2. 3
12.6
1-3 mg/kg
16
9.5
20.0
HR
(95%CI)
0.515
(0.245; 1.081)
0.490
(0.219; 1.096)
P-value
0.075
0.076
Sources: Vey et al., Blood Sept. 21 and ASH 2013 poster
Page 24
EffiKIR positioning in Acute Myeloid Leukemia
Strong medical need for elderly patients
• 5-year survival rate in elderly
patients with AML is 5 to 15%
Treatment paradigm
Patients <60y (<50%)
Patients >60y (>50%)
~ 50%
• No current standard of care for
elderly patients in post-induction
setting
Induction chemotherapy
CR 65-85%
• Intensive development effort in
AML focused on relapsed /
refractory disease
• Lirilumab tested in maintenance
for elderly patients
~ 50%
CR ~ 50%
Consolidation then
transplantation
Consolidation
Maintenance
chemotherapy
EffiKIR trial
TTP: ~ 2 years
< 12 months
Relapse
Mortality (at 5-years):
P <60y (70-80%)
P >60y (85-95%)
Page 25
KIR and NKG2A expression on different subsets of NK cells
Blood NK cells from four healthy donors (one in each panel)
stained for KIR and NKG2A
5%
25%
44%
KIR
26%
30%
12%
25%
33%
49%
2%
36%
23%
36%
10%
34%
20%
NKG2A
Internal data
Page 26
NKG2A expression on tumor infiltrating lymphocytes
Upregulation of NKG2A on
NK cells inside tumors
NKG2A on tumor infiltrating
CD8+ T cells
Lung carcinoma
Cervical cancer
Blood
Tumor
Blood NK (HC)
Intratumoral NK
From L to R : Platonova et al. 2011, Sheu et al. 2005
Page 27
Phase 2 trial of IPH2201 as a single agent in SCCHN
2014
2015
2016
2017
H&N Phase 2 single agent
Patient selection:
• Stage III/IV SCCHN
• Metastatic or recurrent
• HPV + and HPV • Documented PD within 1 month of platinumbased chemotherapy
• < 1 regimen for recurrent or metastatic
disease
Optimum 2-stage Simon
design
• 19 - 39 evaluable
patients
• Primary efficacy
endpoint: PFS at 4
months
• PS 0-1
Regimen:
• IPH2201: 10 mg/kg IV q4 weeks
Page 28
Phase 2 trial of IPH2201 + cetuximab in patients with
platinum-refractory SCCHN
2014
2015
2016
2017
H&N Phase 2 combo cetuximab
Patient selection:
• Stage III/IV SCCHN
Optimum 2-stage Simon
• Platinum Refractory : documented PD within design
• Metastatic or recurrent
1 month of platinum –based chemotherapy
• No prior cetuximab or other EGFR therapy
• PS 0-1
• 19 - 34 evaluable patients
• Primary endpoint:
RECIST Overall RR
Regimen:
• Cetuximab: 400mg/m2 IV then 250 mg/m2
IV weekly + IPH2201: 10 mg/kg IV q 4weeks
• Until PD or untoward toxicity
Page 29
Phase 2 trial of IPH2201+ ibrutinib in relapsed CLL
2014
2015
2016
2017
CLL Phase 2 combo ibrutinib
Patient selection:
• Relapsed refractory CLL
• ≥ 2 prior regimens
Optimum 2-stage Simon
design
• 10 – 29 evaluable patients
• PS 0-1
• Neutro ≥ 750, platelets ≥ 50,000
Regimen:
• Ibrutinib: 420 mg/d p.o. + IPH2201:
10 mg/kg IV q 4 weeks
Primary endpoint
• CR (International
workshop on CLL; bone
marrow biopsy
confirmation)
• Until PD or untoward toxicity
Page 30
Phase 2 trial of single agent IPH2201
in ovarian cancer
2014
2015
2016
2017
Ovarian Phase 2 single agent
Patient selection:
• Platinum resistant ovarian, peritoneal or
tubal carcinoma with progression within
1-6 months of completing platinum-based
chemotherapy
• ≤ 2 prior regimens for recurrent disease
• PS 0-2
• N = 25
• Primary endpoint:
PFS at 4 months
Regimen:
• IPH2201, 10 mg/kg IV q4 weeks up to
progression or untoward toxicity
Page 31
Phase 2 trial of IPH2201 combined with chemotherapy
in platinum-resistant ovarian cancer
2014
2015
2016
2017
Ovarian Phase 2 combo SOC
Patient selection:
• Platinum-resistant disease (disease progression within
<6 months of platinum therapy)
• ≤ 2 prior chemotherapy regimens
• ECOG performance status of 0-2
Regimen:
Optimum 2 –stage Simon
design
• 15 – 35 evaluable patients
• Primary endpoint:
Overall response rate
• Physician choice + IPH2201 10 mg/kg IV q4 weeks
• Physician choice: Gemcitabine, topotecan or Doxil/Caelyx
(Pegylated liposomal doxorubicin,PLD)
• Until disease progression or untoward toxicity
Page 32
Bibliography
Lirilumab, anti-KIR
o
Kohrt et al., 2014. Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in
combination with anti-CD20 antibodies. Blood
o
Vey et al., 2012. A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in CR. Blood
o
Romagne et al., 2009. Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that
augments natural killer-mediated killing of tumor cells. Blood
o
Vahlne et al., 2010. In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: maintained tolerance to normal
cells even in the presence of IL-2. European journal of immunology
o
Moretta et al., 2008. Human NK cells: from HLA class I-specific killer Ig-like receptors to the therapy of acute leukemias.
Immunological reviews
o
Ruggeri et al., 2002. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science
IPH4102, anti-KIR3DL2
o
o
Bouaziz et al., 2010. Absolute CD3+ CD158k+ lymphocyte count is reliable and more sensitive than cytomorphology to
evaluate blood tumour burden in Sezary syndrome. The British journal of dermatology
Bagot et al., 2001. CD4(+) cutaneous T-cell lymphoma cells express the p140-killer cell immunoglobulin-like receptor. Blood
IPH43, anti-MICA
o
Bauer et al., 1999. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science
o
Holdenrieder et al., 2006. Soluble MICA in malignant diseases. International journal of cancer.
o
Champsaur, M., and L.L. Lanier. 2010. Effect of NKG2D ligand expression on host immune responses. Immunological reviews
See IPH website for direct links to bibliography Page 33
Bibliography
IPH2201, anti-NKG2A
o
Levy et al., 2008. HLA-E protein is overexpressed in primary human colorectal cancer. International journal of oncology
o
Iwaszko et al., 2011. Clinical significance of the HLA-E and CD94/NKG2 interaction. Archivum immunologiae et therapiae
experimentalis
o
Gunturi et al., 2005. The role of TCR stimulation and TGF-beta in controlling the expression of CD94/NKG2A receptors on
CD8 T cells. European journal of immunology
o
Mamessier et al., 2011. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor
immunity. The Journal of clinical investigation
o
Derre et al., 2006. Expression and release of HLA-E by melanoma cells and melanocytes: potential impact on the response of
cytotoxic effector cells. J Immunol
o
Malmberg et al., 2002. IFN-gamma protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2Adependent mechanism. The Journal of clinical investigation
o
Levy et al., 2009. Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells.
Innate immunity
o
Godal et al., 2010. NK cell killing of AML and ALL blasts by killer cell Ig-like receptor-negative NK cells after NKG2A and LIR-1
blockade. Journal of the American Society for Blood and Marrow Transplantation
o
Nguyen et al., 2005. NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells
and inhibitory effect of NKG2A override GvL effect. Blood
IPH33, anti-TLR3
o
o
Cavassani et al., 2008. TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. The Journal of
experimental medicine
Le Goffic et al., 2007. Cutting Edge: Influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral
responses in human lung epithelial cells. J Immunol.
See IPH website for direct links to bibliography
Page 34
Key figures
Year ended December
In thousands of euros
Revenue from collaboration and licensing agreements
2013
2012
12,469
10,377
4,182
3,905
16,652
14,282
Research and development expenses
(15,131)
(13,417)
General and administrative expenses
(4,313)
(4,251)
Net operating expenses
(19,444)
(17,668)
(2,792)
(3,386)
(99)
185
(2,892)
(3,199)
Weighted average number of shares (in thousands):
38,703
37,802
Net loss per share
(0.07)
(0.08)
Government financing for research expenditures
Revenue and other income
Operating income / (loss)
Financial result
Net income / (loss)
• Cash & cash equivalents as at the end of 1Q 2014: €37.2m
Page 35
Investor relations
Laure-Hélène Mercier
Director, Investor relations
[email protected]
Tel: +33 (0)4 30 30 30 87
Fax: +33 (0)4 30 30 30 30
Page 36

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