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Have the courage to innovate without borders and make evidence-based decisions
to deliver solutions that address real patient needs
AiM Institute hhc mission statement
Delivering NextGen Targeted Immunotherapies
Myeloid lineage targeting therapeutics to address
unmet needs in immuno-oncology
Eisai Scientific Day
Nadeem Sarwar
President, Eisai AiM Institute Andover innovative Medicines
99
Our generation of drug discoverers
have the tools needed to cure cancers
100
Unprecedented hope for cancer patients:
but only small subset of patients currently benefit
Immunotherapies & precision medicines provide most powerful arsenal
ever available in fight against cancer
Considerable and unmet residual needs remains
Game changing scientific discoveries have driven unprecedented
translational investments
101
*1: Genomics England: A genome analysis project in the UK involving more than 100,000 people
*2: Cancer MoonShot: A $ 1 billion national project in the US led by the Vice president Joe Biden aiming to make more cancer therapies available to more patients
*3: Parker Institute for Cancer Immunotherapy in US: A collaboration between the country's leading immunologists and cancer centers, established by Sean Parker aiming for cancer cure
*4: Bloomberg-Kimmel Institute: A new institute for cancer immunotherapy research established in John’s Hopkins University with support from Michael R. Bloomberg, Sydney Kimmel and others.
Genomics England*1
Cancer MoonShot Initiative*2
Parker Institute*3
Bloomberg-Kimmel Institute*4
……….
NextGen precision immunotherapeutics:
Targeting the tumor microenvironment
The tumor and its cellular environment are interdependent, with both defining the extent of:
immune tolerance, growth, evolution
Tumor
Microenvironment
102
Novel immune-microenvironment clues from an old source:
Aspirin, prostalandins and myeloid cells
Aspirin may reduce risk of several cancers –
MoA likely prostaglandin and myeloid cell driven
11,000 participant RCT
of cancer prevention
Potent and specific modulation of EP receptors may provide
novel therapeutic opportunity for targeting tumor immune microenvironment
Reduction in cancer incidence associated
with aspirin in large-scale meta-analyses:
Esophageal: 30%
Stomach: 30%
Colorectal: 35%
Adapted from Rothwell et al. Several
103
Prostaglandin E2 (PGE2) signaling disrupts anti-tumor activity of
immune cells
Macrophage
Dendritic cell
T-cell
EP4 receptor
EP2
Investigational E7046: First in Class EP4 Specific Antagonist
Reverses of PGE2-mediated tumor promotion and immune suppression
E7046 PGE2
104
E7046 clinical plan and status
RP2D
Submission
Phase I:
Open-labeled multi-center study
Selected cancers with high myeloid cell infiltration
Collection of multiomic data, samples and FDG-PET
Phase 1b/2 with CRT:
Open labeled multi-center combination study
PET tracer development currently ongoing
Combination with pre-operative radiotherapy in locally advanced rectal cancer
Regulatory Activities
/Full Development
101 Study:
Monotherapy,
RP2D (Recommended
Phase 2 Dose)
RT/CRT
comb. (Radiotherapy/
Chemo-
radiotherapy)
FY2015 FY2016 FY2017 FY2018 FY2019 FY2020
Ph-1
Ph-1b comb.
Ph-2 comb. CRT
105
Available immunotherapies provide unprecedented hope for subsets of
oncology patients in whom such therapies work
Immunosuppresive myeloid cell lineage in tumor microenvironment
provide novel and complementary path to address unmet patient needs
Our first in class EP4 receptor antagonist – E7046 – currently in clinical
development provides a unique opportunity to test this hypothesis
Integration of large-scale multi-omic and imaging data being employed to
identify right target, right tumor, right patient & right dose for E7046
106
Eisai Scientific Day
Takashi Owa, Ph.D.
Chief Medicine Creation Officer
Oncology Business Group
“Ricchi” and Innovation in Small Molecule
Science to Target Cancer Microenvironment
at Tsukuba Research Laboratories (TRL)
107
Eribulin New Mechanisms of Action
1. Tubulin-based Antimitotic Effects
2. Complex Non-Mitotic Effects on Cancer Biology
1) Tumor Vasculature Remodeling
2) Reversal of Epithelial-Mesenchymal Transition (EMT)
3) Inhibition of Cancer Metastasis
4) Inhibition of Cancer Stem Cells
Linked with Phenotypic Changes in Cancer Cells and Cancer Microenvironment
Agoulnik et al., Dezso et al., Matsui et al., and McCracken et al., 2013 AACR Meeting;
Yoshida et al., 2013 AACR-NCI-EORTC; Funahashi et al., 2014; Yoshida et al., Br J Cancer, 2014
108
After a Single Dose of Eribulin, Perfusion
Becomes Uniform Across Tumor Core and Rim
with MX-1 human breast cancer xenografts (day 6)
Vehicle
Well perfused
Poorly perfused,
hypoxic area
Uniform perfusion,
tumor shrinkage
Eribulin, 0.3 mg/kg
Funahashi et al., 2014
DCE-MRI of representative tumors in vehicle- or eribulin-treated nude rats
109
Eribulin Reverses EMT in Tumors In Vivo
MX-1 human breast cancer cells xenografts in vivo
(single dose, 8 days, nude mice)
Yoshida et al., 2014
Epithelial marker
Mesenchymal markers
110
Eribulin Prevents Experimental Metastasis
and Increases Survival in Mice
Number of lung nodules
Yoshida et al., 2014
Survival of mice
Inject eribulin-treated or 5FU-
treated surviving breast cancer
cells into tail vein
111
Anti-Cancer Stem Cell Activity with Eribulin in the In Vivo
Serial Transplantation Model of HSAEC RD Cells
112
Control
PTX QD5 20 mg/kg
ERI Q4D3 1 mg/kg
Day
Tum
or
volu
me
(mm
3)
HSAEC RD lung cancer xenograft
Serial transplantation
Control
PTX Eribulin
( N = 10 )
HSAEC RD: Human small airway epithelial cell infected with retroviral vectors expressing KRASV12 (R) and CYCLIN-D1 (D)
Cell number
112
Presentation at AACR 2016 Shows Human Biology Evidence
on Eribulin New MOAs
• 52 patients with locally advanced or metastatic breast cancer treated with eribulin
• Before/after biopsies from 10 patients • Correlated response rate (RR) with immunohistochemical evaluation:
o TILS: PD-1, CD8, FOXP3 o Cancer cells: PD-L1, PD-L2 o EMT markers: E-cadherin, N-cadherin, vimentin, CA9
Conclusions • Statistically significant correlations
between clinical RR and change in marker status for PD-L1 (p = 0.024) FOXP3 (p = 0.004) E-cadherin (p = 0.004) CA9 (p = 0.024)
• Immune suppression markers (PD-L1, FOXP3) going negative correlated with Clinical RR Reversal of EMT (E-cadherin going
up)
• Loss of hypoxia (CA9 going down) correlated with clinical RR
113
Halichondrin Family
Cytotoxicity against B-16 melanoma cells
IC50 (nM)
Halichondrin B 12.5 mg C 7.2 mg
Norhalichondrin A 35.0 mg B 4.2 mg C 2.4 mg
Homohalichondrin A 17.2 mg B 3.1 mg C 2.1 mg
0.083 0.31 4.6 - - 0.23 0.089 -
Halichondria okadai Kadota 600 kg
• Isolation, structure determination and biological activity:
Hirata, Uemura et al J. Am. Chem. Soc. 1985, 107, 4796; Pure Appl. Chem. 1986, 58, 701.
• For isolation from different species of sponges, see:
Pettit et al J. Med. Chem. 1991, 34, 3339; J. Org. Chem. 1993, 58, 2538.
Blunt, Munro et al Tetrahedron Lett. 1994, 35, 9435; J. Org. Chem. 1997, 62. 1868; Bioorg. Med. Chem. 2009, 17, 2199. 114
Halichondrin B In Vitro Antiproliferative Profile
115
Eribulin
(NSC 707389)
Halichondrin B
(NSC 609395)
GI50 values from NCI-60 cell panel analysis
https://dtp.cancer.gov/timeline/posters/Halichondrin.pdf
Halichondrin B In Vivo Antitumor Profile
116
LOX melanoma s.c. xenograft model
in nude mice
LOX melanoma bone marrow metastasis model
in nude rats
Halichondrin B
Vinblastine
Halichondrin B
Vinblastine
Vehicle
Days Su
rviv
al (
%)
The i.v. treatment schedules and doses were 20 mg/kg Q2D5 for halichondrin B (-□-) and homohalichondrin B (-◆-) given i.v. and 4 mg/kg Q7D2 i.v. for vinblastine (-◇-). Control animals (-■-) were treated with saline at Q2D5 schedule.
Animals were injected intracardially with 1 x 106 LOX cells day 0 , and the i.p. treatments of halichondrin B (9 mg/kg, Q2D5) , vinblastine (1.8 mg/kg, Q7D2) and saline (Q2D5) were started on day 7.
J Exp Ther Oncol. 1996;1(2):119-25
Lenvatinib Combination with Anti-PD-1 Therapy
Scientific Rationale
Lenvatinib reduces immune suppressive myeloid derived cells (TAM) and induce activated cytotoxic T cells (CD8 T-cell) , promoting antitumor activity of anti-PD-1 therapy.
Kato et al., EORTC-NCI-AACR 2015
117
Lenvatinib Combination with Anti-PD-1 Therapy
Lenvatinib reduces immune suppressive myeloid derived cells and induce activated
cytotoxic T cells, promoting antitumor activity of anti-PD-1 therapy
TAM
VEGF CSF
Treg
TCR
MHC Antigen
CTL
Cancer
Monocyte
TGF-b
TAM
TCR
MHC Antigen
Cancer
Monocyte
Attack
PD-1
CTL
PD-L1
TAM
Decrease
Immune Inhibitory Cytokine (TGF-b)
Down
Immune Inhibitory Receptor
(PD-1, Lag3) Down
Immune Stimulatory cytokine(IL12)
Up
PD-1 Ab
Lenvatinib (VEGF blockade)
IFNg
Immune suppressive tumor microenvironment
Lenvatinib causes Immune stimulating tumor microenvironment
Improved antitumor activity of anti-PD-1 therapy
Rayman et al. also reported the similar MOA for sunitinib with
PD-1 blockade in the mouse RCC model (SITC 2015)
TAM secretes TGF-b, which activates immune suppressive Treg and inhibits cytotoxic T cells.
PD-L1 expressed on tumor cells activate PD-1 and suppressed CTL
118
Kato et al., EORTC-NCI-AACR 2015
Cancer Stemness Platform in TRL (1)
AXL inhibitor Targeting Mesenchymal Cancer Cells &
Tumor Vessel Formation
AXL is a key regulator for mesenchymal cancer (stem-like) cells & tumor vessel formation.
Activation of AXL and concomitant epithelial-mesenchymal transition (EMT) were reported in EGFR-mutant NSCLC with acquired resistance to erlotinib. Nat Genet., 44, 852 (2012) AXL was identified as a mesenchymal marker gene associated with innate anti-PD-1 resistance in melanoma patients. Cell, 165, 35 (2016) A clinical sample of triple negative breast cancer after weekly paclitaxel treatment showed upregulation of AXL expression.
AXL/Gas6 signaling was shown to accelerate the formation of pericyte covered tumor vessels resistant to anti-VEGF therapies. Cancer Res., 65, 9294 (2005)
119
Endothelial cell (EC)
Smooth muscle cell (SMC)
Cancer cell
Autocrine/paracrine AXL/Gas6 signaling
EC migration, proliferation.
and survival
SMC migration,
proliferation and survival
Cancer cell EMT
AXL IHC staining
Cancer Stemness Platform in TRL (2)
ALDH (Aldehyde Dehydrogenase) Inhibitor Targeting Cancer Stemness
ALDH consists of 19 isoforms • ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH1L1, ALDH1L2
• ALDH2
• ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2
• ALDH4A1, ALDH5A1, ALDH6A1, ALDH7A1, ALDH8A1,
ALDH9A1, ALDH16A1, ALDH18A1
1. High ALDH expression in variety of cancers 2. Upregulation of ALDH expression after chemotherapy 3. Positive correlation between ALDH expression and tumor grade relevant to poor prognosis
• Kaplan–Meier curves among ALDH1(-) and ALDH1(+) patients with all breast cancer subtypes showed a statistically significant correlation between ALDH(+) status and shorter disease-free survival (DFS)/overall survival (OS): Breast Cancer Res Treat., 156, 261 (2016).
4. ALDH knock-down led to suppression of cancer stem-like properties in vitro and tumor growth in vivo.
120
Stemness markers
In vitro In vivo H358 s.c. model
Oncology “Ricchi” and Innovation to
Provide Cure with Particular Focus on
Cancer Genomics and Cancer Microenvironment
Epithelial cancer cells
Mesenchymal cancer cells
Myeloid cells
Lymphoid cells
Cancer stem cells
Endothelial cells
EMT*1 MET*2
Mesenchymal stromal cells
(Fibroblasts, etc.)
Cytotoxics
1st generation RTKIs*3
Immune checkpoint
inhibitors
Angiogenesis
inhibitors
TRL Platform
Lenvatinib/Eribulin
H3B Platform
Cancer genomics
Splicing
AIM Institute Platform Prostaglandin receptors
TRL Platform
Eribulin/Cancer Stemness
TRL Platform
Lenvatinib
MOR Platform
Anti-TEM-1 Ab
*1 Epithelial-Mesenchymal Transition *2 Mesenchymal-Epithelial Transition
*3 Receptor tyrosine kinase inhibitors 121
Alton B. Kremer MD, PhD
Chief Clinical Officer
Chief Medical Officer
Key Global Assets
Eribulin and Lenvatinib:
Toward Establishing
New Treatment Paradigms
Eisai Scientific Day
122
Mechanism of Action of Lenvatinib
RAS
RAF
T202/Y204
MEK
PI3K
AKT
mTOR
Lenvatinib
S6K
S6
P P
P
ERK1/2 P
S235/S236
T389
T421/S424
Angiogenesis
FGFR VEGFR
Adapted from Stjepanovic N, Capdevila J. Biologics: Targets and Therapy. 2014:8;129-139; Eisai data on file.
123
Proposed Mechanism of Interaction
Between Lenvatinib and Everolimus
Everolimus
RAS
RAF
T202/Y204
MEK
PI3K
AKT
mTOR
Lenvatinib
S6K
S6
P P
P
ERK1/2 P
S235/S236
T389
T421/S424
Angiogenesis
FGFR VEGFR
Adapted from Stjepanovic N, Capdevila J. Biologics: Targets and Therapy. 2014:8;129-139; Eisai data on file. 124
Laboratory Rationale for the Combination of
Lenvatinib with Everolimus
Complementary activities of lenvatinib plus everolimus
Enhancement of the inhibitory activity against VEGF-induced angiogenesis by the combination of lenvatinib with everolimus
Synergistic enhancement of the inhibitory activity against FGF-induced angiogenesis by the combination
Combination of potent antiangiogenic activity as well as direct antitumor activity by the combination
Dual targeting of the mTOR-S6K-S6 pathway by the combination
Source: Module 2.6.2, Discussion and Conclusion 125
Phase II Study in Renal Cell Carcinoma (RCC)
(Study 205, NCT01136733)
Global, randomized, open-label, phase II trial
Key eligibility criteria
• Advanced or
metastatic RCC
• Measurable disease
• Progression on or
within
9 months from prior
treatment
• Progression on/after
1 prior VEGF-targeted
therapy
• Eastern Cooperative
Oncology Group
Performance Status
(ECOGPS) ≤ 1
Lenvatinib, 18 mg
+ Everolimus, 5 mg
Both PO once daily
n = 51
•
Lenvatinib 24 mg PO qd
n = 52
•
Everolimus 10 mg PO qd
n = 50
Primary endpoints
• Progression-free
Survival*
LEN/EVE vs EVE
LEN vs EVE
Selected secondary
endpoints
• Progression-free
Survival
LEN/EVE vs LEN
• Objective
Response Rate
• Overall Survival
• Safety and
tolerability
1:1:1
R
A
N
D
O
M
I
Z
E
Treatment until
disease progression or unacceptable toxicity
*Based on investigator review and RECIST v1.1 126
Kaplan-Meier Plot of Progression-Free Survival
(Investigator Assessment – Study 205)
0.0
0.2
0.4
0.6
0.8
1.0
0 3 6 9 12 15 18 21 24
Pro
gre
ss
ion
-Fre
e S
urv
iva
l
Time (months) Number at risk:
Lenvatinib/Everolimus 51 41 27 23 16 10 5 1 0
Everolimus 50 29 15 11 7 3 1 0 0
+ +
LEN+EVE
(n = 51) EVE
(n = 50)
PFS, months, median
(95% CI) 14.6 (5.9-20.1) 5.5 (3.5-7.1)
HR vs everolimus
95% CI 0.40
(0.24-0.68)
+ +
United States Package Insert. *Internal data
After post-hoc multiplicity adjustment with the Bonferroni method, the adjusted P value for lenvatinib/everolimus compared with single agent everolimus was P = 0.0011*
127
Lenvatinib 18 mg +
Everolimus 5 mg
(n=51)
Everolimus 10 mg
(n=50)
Progression-Free Survival (PFS)a
Median PFS in months (95% CI) 14.6 (5.9, 20.1) 5.5 (3.5, 7.1)
Hazard Ratio (95% CI)b
Lenvatinib + Everolimus vs Everolimus
0.37 (0.22, 0.62) −
Overall Survivalc
Median OS in months (95% CI) 25.5 (16.4, 32.1) 15.4 (11.8, 20.6)
Hazard Ratio (95% CI)b
Lenvatinib + Everolimus vs Everolimus
0.67 (0.42, 1.08) −
Objective Response Rate (Confirmed)
Objective response rate, n (%) 19 (37) 3 (6)
(95% CI) (24, 52) (1, 17)
Tumor assessments were based on RECIST v1.1 criteria for progression but only confirmed responses are included for ORR.
Data cutoff date = 13 Jun 2014
CI = confidence interval
a. Point estimates are based on Kaplan-Meier method and 95% CIs are based on the Greenwood formula using log-log transformation.
b. Hazard ratio is based on a stratified Cox regression model including treatment as a
covariate factor and hemoglobin and corrected serum calcium as strata.
c. Data cutoff date = 31 Jul 2015
Efficacy Results in Renal Cell Carcinoma
(Investigator Assessment – Study 205)
128
FDA Approval
On May 13, the U.S. Food and Drug Administration (FDA) approved lenvatinib capsules (18 mg) in combination with everolimus (5 mg) for the treatment of patients with advanced renal cell carcinoma (aRCC) who were previously treated with an anti-angiogenic therapy, which is a standard of care for this disease.
This was a Priority Review following Breakthrough Therapy Designation
The first and only FDA-approved combination of a multiple receptor tyrosine kinase inhibitor (lenvatinib) and an mTOR inhibitor (everolimus) for the treatment of advanced RCC
129
Phase III Study in Renal Cell Carcinoma (RCC)
Study 307, to open Sept 2016
Global, randomized, open-label, phase III trial
Key eligibility criteria
• Age ≥18 years
• Advanced RCC with a
clear-cell component and
histologic / cytologic
confirmation
• No prior systemic
anticancer therapy for
RCC
• Karnofsky Performance
Score ≥70
Lenvatinib 18 mg orally once daily
+ Everolimus 5 mg orally once daily
•
Lenvatinib 20 mg orally once daily
+ Pembrolizumab 200 mg IV every 3 weeks
•
Sunitinib 50 mg orally once daily
4 weeks on / 2 weeks off
Primary endpoints
• PFS (independent
imaging review
using RECIST 1.1)
Secondary endpoints
• ORR
• OS
• Safety and
tolerability
Selected exploratory
endpoints
• HRQoL
• DOR
• PK/PD
• Biomarkers
1:1:1
n = ~735
R
A
N
D
O
M
I
Z
E
Treatment until
disease progression
or unacceptable toxicity
Stratification factors:
• Geography
(Western Europe and North
America, Rest of World)
• MSCKK prognostic group
(Low, Intermediate, High)
130
First Line RCC Study 307:
Key Target Dates
Study Open
September 2016
Database lock
December 2019
Topline results
4Q FY2019
131
Phase III Study in Investigational
Hepatocellular Carcinoma (HCC)
(Study 304, NCT01761266)
Key eligibility
criteria
(N = 940)
• Confirmed
unresectable HCC
• Measurable
disease by
mRECIST
• Barcelona Clinic
Liver Cancer Stage
B or C
• Child-Pugh score A
• ECOG PS:0 or 1
• No prior anticancer
agents
R
A
N
D
O
M
I
Z
E
1 : 1
Lenvatinib
12 or 8 mg daily PO
(based on body
weight)
Sorafenib
400 mg daily PO
BID
Primary endpoint
• Overall Survival
Selected secondary
endpoints
• Progression-free
Survival
• Time to Progression
• Objective Response
Rate
• Safety and
tolerability
• PK parameters
• Quality of life
Treatment until
disease
progression (mRECIST)
Stratification • Geographic
Region
• Macroscopic
portal vein
invasion or
extrahepatic
spread or both
(No/Yes)
• ECOG (0/1)
• Body weight
(< 60 kg/ ≥ 60 kg)
132
Phase Ib/II Study of Lenvatinib +
Pembrolizumab in Selected Solid Tumors
(Study 111, NCT02501096)
Phase Ib Phase II (opened 31 Jan 2016)
Lenvatinib 20 mg QD (RP2D)
+ Pembrolizumab 200 mg Q3W
(21-day cycle)
n = 60-120
Renal Cell (20)*
Melanoma (7)
Urothelial (6)
NSCLC (1)
Endometrial (20)
SCCHN (5)
* Number Of Subjects Enrolled As Of 23 June 2016
Cohort Lenvatinib Pembrolizumab
1A 24 mg 200 mg
2A 20 mg 200 mg 3A 14 mg 200 mg
Same tumor types as Phase 2
n = 10 – 30 subjects (13 subjects actual)
133
Study in planning: Phase Ib Study of Lenvatinib
+ Pembrolizumab in Hepatocellular Carcinoma
(Study 116)
DLT evaluation part
• N=6-10
• Starting dose of
lenvatinib:
12mg QD (BW ≥ 60 kg)
/8 mg QD (BW < 60 kg)
• Dose of pembrolizumab:
200mg /Q3W
• BCLC: Stage B or C
• Child-Pugh A
• ECOG PS: 0-1
Expansion part
• No prior
systemic
therapy
• N=20
(10 in Japan
/10 in US)
Primary endpoints
• MTD & RP2D for combination
of lenvatinib + pembrolizumab
Selected secondary endpoints
• Safety and tolerability
• Efficacy: ORR/ PFS/ OS/
Duration of response
(Tumor assessments to be
performed using irRECIST)
• Pharmacokinetics
• Blood / tumor biomarkers
134
Phase Ib/II Study of Eribulin + Pembrolizumab in
Metastatic Triple-Negative Breast Cancer
(Study 218, NCT02513472)
Key eligibility criteria
• Aged 18 years or greater
• 0-2 prior lines of
chemotherapy for
metastatic disease
• Measurable disease
• ECOG PS:0 or 1
• Adequate bone marrow,
renal, and hepatic
function
Primary endpoints
• Dose-limiting
Toxicities
• Objective
Response Rate
Selected secondary
endpoints
• Progression-free
Survival
• Overall Survival
• Duration of
Response
• Outcomes in the
PD-L1–positive
subgroup
• Safety and
Tolerability
Eribulin 1.4 mg/m2 on Days 1, 8
+ Pembrolizumab 200 mg on Day 1
(21-day cycle)
n = approximately 95
Current enrollment: 85 patients*
* Number Of Subjects Enrolled As Of 23 June 2016 135
Current Status of Combinations with PD-1
• Lenvatinib (Study 111)
– Preliminary data to be presented at major conference
– Further studies based on cohort data as they accumulate
– Phase 3 RCC study already planned (Study 307)
• Eribulin (Study 218)
– Preliminary data to be presented at major conference
– Cohorts for patients with urological malignancies to be added
• Total 52 patients
• Cohorts: a) ineligible for cis-platinum; b)following cis-platinum
• Will open October 2016
136
Summary
Lenvatinib has obtained a second line RCC indication in combination with everolimus in the U.S.
We will initiate a phase 3 study in first line RCC in September studying lenvatinib in combination with everolimus and in combination with pembrolizumab
We expect the results of the phase 3 study of lenvatinib in HCC by the end of 2016
Combination studies with pembrolizumab are ongoing with both lenvatinib and eribulin across 8 different tumors
137
Flagship Programs in Oncology
All the compounds shown in this slide are investigational. *1: Collaboration with Merck for the Ph 1b/2 combination study with Pembrolizumab. *2: Collaboration with Halozyme Therapeutics, Inc for the combination with PEGPH20. 138
Combination therapy with pembrolizumab: Ph 1b/2 study is ongoing for Triple-negative breast cancer.
Combination therapy with PEGPH20: Phase Ib/II study site initiation in 1Q FY16. Investigating the potential to treat HER2-negative breast cancer.
Lenvatinib*1
E7046
EP4 Inhibitor
H3B-6527
FGFR4 Inhibitor
H3B-8800
Splice Modulator
Eribulin*1,2
Global, randomized, open-label, Ph 3 study for RCC 1st line is planned to start in September 2016 in combination with pembrolizumab or everolimus.
Global submission for HCC 1st line is planned within FY16. Combination therapy with pembrolizumab: Ph 1b/2 study is ongoing for Lung,
melanoma, head and neck, bladder, renal and endometrial cancer.
Multi-center Ph 1study is ongoing to determine recommended Ph 2 dose. Open-label multi-center Ph 1b/2 study is planned to start in the 2nd half of FY16, a
combination study with pre-operative radiotherapy in locally advanced rectal cancer.
IND approved April 2016, FPFV for Ph 1 study in July 2016 Phase I in advanced, unresectable HCC (with and without cirrhosis) and IHCC (Intra
Hepatic Cholangiocarcinoma)
Clinical proof of concept is planned in patients with high FGF19 expression
IND approved April 2016, FPFV for Ph 1 study in July 2016 Ph1 in advanced myeloid malignancies, with multiple expansion arms to probe
activity in selected patients with MDS, CMML and AML. Potential Ph2 registrational trials in splice factor mutant-positive patients with MDS.
Can
cer
Gen
e
Dep
en
den
ce a
nd
Ab
err
an
t S
plicin
g
En
do
thelial
cells
Launch target: FY2020
Launch target: Beyond FY2020
Launch target: FY2017 for HCC
Can
cer
Mic
roen
vir
on
men
t
Eisai Scientific Day
Closing Remarks
Haruo Naito, KBE
CEO
139
TO THE LARGEST UNMET MEDICAL NEEDS
OF THE GLOBE “AD/DEMENTIA”,
WE WILL PROVIDE
A VARIETY OF PREEMPTIVE OPPORTUNITIES
BY USING DIFFERENT MOA AGENTS
140
UTILIZING OUR WORLD-CLASS
SMALL MOLECULE SCIENCE,
AND FOCUSING ON
“CANCER MICROENVIRONMENT”
AND “ONCOGENOMICS”,
WE WILL AIM CURE OF CANCERS