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