Eisai Way Toward Sustainable Value Creation
37TH ANNUAL J.P. MORGAN HEALTHCARE CONFERENCE

Ryohei Yanagi, Ph.D.
CFO (Chief Financial Officer), Chief IR Officer

Ivan Cheung
Chairman & CEO, Eisai Inc. (USA)January 9, 2019
Eisai Co., LtdSafe Harbor Statement
 Forecast or target figures in this material are not official earnings guidance but represent midterm strategies, goals, and visions. Official
earnings guidance should be referred to in the disclosure of the annual financial report (Consolidated Financial Statement) in accordance withthe rules set by Tokyo Stock Exchange.
 Materials and information provided during this presentation may contain so-called “forward-looking statements.” These statements are basedon current expectations, forecasts and assumptions that are subject to risks and uncertainties that could cause actual outcomes and results todiffer materially from these statements.
 Risks and uncertainties include general industry and market conditions, and general domestic and international economic conditions such as
interest rate and currency exchange fluctuations. Risks and uncertainties particularly apply with respect to product-related forward-looking
statements. Product risks and uncertainties include, but are not limited to, technological advances and patents attained by competitors;
challenges inherent in new product development, including completion of clinical trials; claims and concerns about product safety and efficacy;
regulatory agency examination periods and obtaining regulatory approvals; domestic and foreign healthcare reforms; trends toward managed
care and healthcare cost containment; and governmental laws and regulations affecting domestic and foreign operations.
 Furthermore, for products that are approved, there are manufacturing and marketing risks and uncertainties, which include, but are not limited
to, inability to build production capacity to meet demand, unavailability of raw materials, and failure to gain market acceptance.

 The Company cannot guarantee the actual outcomes and results for any forward-looking statements.
 The Company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information,
future events or otherwise.
 The English-language presentation was translated from the original Japanese-language version. In the event of any inconsistency between thestatements in the two versions, the statements in the Japanese-language version shall prevail.

 The Company discloses its consolidated financial statements according to the International Financial Reporting Standards (IFRS).

2

Corporate Philosophy

Striving to be a human health care (hhc) Company
Eisai’s Value Creation Process and Flow

Chain of Targets and Results3Non-Financial Capital andEquity Spread Value Relevance Model*1
*1
*2

*1
4

*2

Striving for Sustainable Corporate Value Creation by Enhancing Non-Financial Capital

IIRC-PBR Model

Value relevance of the six capitals that compose corporate value
Net assets (book value on accounting basis) is related to financial capitaland Market Value Added (MVA) is related to non-financial

5Neurology(Mainly Alzheimer’s Disease Including
Collaboration with Biogen)

6

BAN2401 from Study 201*1

Suggested disease modifying effect (1)Adjusted mean difference from placebo group in ADCOMS*3

CLINICAL IMPROVEMENT

Correlation of ADCOMS*2 and PET SUVr
rp = 0.838• Correlation of amyloid
clearance in the brain andimprovement in clinicalsymptom decline with BAN2401
administration was observed(rp=0.838)

Adjusted mean difference from placebo group in PET SUVr*3

AMYLOID CLEARANCE

N with 18 months
PET data
7

10 mg/kg
bi-weekly

10 mg/kg
monthly

5 mg/kg
bi-weekly

5 mg/kgmonthly

2.5 mg/kg
bi-weekly

37

82

24

23

23

Note: rp is Pearson’s correlation coefficient *1: Investigational. Co-development with Biogen. Licensed in from BioArctic *2: ADCOMS: Alzheimer’s Disease Composite Score *3: Adjusted mean was based on a protocolspecified mixed effects model with repeated measures (MMRM). The MMRM model included baseline as a covariate, with treatment group, visit, region, randomization stratification variables (clinical stage, concurrent
AD medication, APOE4 status), and treatment group-by-visit interaction as fixed effects. Data shown are for subjects enrolled in the PET sub-study with PET SUVr and clinical data at 12 or 18 months (N=288)

BAN2401 from Study 201*1

Suggested disease modifying effect (2)Slope analysis of ADCOMS*2

Estimated mean change from baseline

WORSENING

0.00• BAN2401 significantly slows rate of
disease progression
at the highest dose arm*3 comparedto placebo (p<0.001)

Slope = 0.0060
P<0.001-0.05• Significant treatment effect for
disease progression of AD
during treatment period is observedin BAN2401 arm, and also suggests
sustainable treatment effect andpotentially expanded treatment
effect over time

-0.10

-0.15

Slope
0.0083
傾き==0.0083
Placebo

10mg/kg bi-weekly

-0.20
0

8

6

12

18

months*1: Investigational. Co-development with Biogen. Licensed in from BioArctic*2: Linear regression model testing the slope of change from baseline. Slopes shown represent change in ADCOMS (Alzheimer’s Disease Composite Score) per month.
Sample size including 238 from placebo arm and 152 from 10mg/kg bi-weekly arm*3: 10 mg/kg bi-weekly

BAN2401 from Study 201*1

Median change from baseline
at 18 months (pg/ml)

Suggested disease modifying effect (3)Median change from baseline
at 18 months (pg/ml)

N with 18 mo. data
Interquartile range (Q1, Q3)

Median change from baseline
at 18 months (pg/ml)

N with 18 mo. data
Interquartile range (Q1, Q3)

N with 18 mo. data
Interquartile range (Q1, Q3)

9

CSF*2 biomarker data
+0.01

Reduction of phospho-Tau (p-Tau)-12
Placebo
16(-2, 12)Combined 10 mg/kg*3
23(-20, 1)

+13.5

Reduction of neurogranin-58
Placebo
16(-91, 32)

• Phospho-Tau181 (p-Tau) is a CSF marker for nerve damage downstream of Tau
pathway, that correlates with tau pathology• CSF p-Tau level is elevated in subjects with AD*4
• BAN2401 significantly reduces CSF p-Tau levels by 13% (12 pg/ml median reduction
from baseline) over 18 months

Combined 10 mg/kg*3• Neurogranin is a synaptic protein and a CSF marker of synaptic damage by
neurodegeneration• CSF neurogranin levels are elevated in subjects with early AD*5
• BAN2401 reduces CSF neurogranin levels by 11% (58 pg/ml median reduction frombaseline) over 18 months

23(-97, 8)

48%

+156

Observeddifference
vs. placebo+75

Slowing increase in neurofilament light chain (NfL)• Neurofilament light chain (NfL) is a neuronal structural scaffold protein and a CSF
marker of axonal degeneration*6 by neurodegeneration• CSF NfL levels are elevated in subjects with AD• BAN2401 slows increase in NfL in the CSF by 48% (median difference) compared toplacebo over 18 months

Placebo Combined 10 mg/kg*3
16(92, 195)

23(16, 188)*1: Investigational. Co-development with Biogen. Licensed in from BioArctic. *2: Cerebrospinal fluid *3: Subjects randomized to 10 mg/kg bi-weekly and 10 mg/kg monthly dose groups combined*4: Zetterberg H et al. J Alzheimers Dis. 2007 Nov;12(3):255-60 *5: Kvartsberg H et al. Alzheimer’s Dementia 2015; 11(10):1180-90 *6: Khalil M et al. Nat Rev Neurol. 2018; 14(10):577-589

BAN2401 from Study 201*1

Suggested treatment effect on Early AD

Amyloid➡Tau➡Neurodegeneration
Amyloid

Tau• Significant amyloid
clearance confirmed
through PET in theoverall population• CSF biomarker
that indicates
improvement ofpathophysiology• Over 80% of subjects
at highest doseconverted frompositive to negative
confirmed throughamyloid PET*2• Amyloid PET data
significant acrosssubgroups*3

10*4

Neurodegeneration• CSF biomarker
that indicates
improvement ofneurodegeneration- Inhibit nerve damage - Protect synapse(Reduction ofdownstream of Tau
neurogranin)
pathway(Reduction of p-Tau)- Inhibition of axonal
degeneration(Slow to increase of
NfL)

Clinical outcome• Observed effect to slow
cognitive decline ineach evaluation items inhighest dose arm
30% less cognitive
decline in ADCOMS*5• Observed less cognitive
decline acrosssubgroups*3•Expansion of treatment
effect is observed forthe entire treatment
period*1: Investigational. Co-development with Biogen. Licensed in from BioArctic *2: 81% converted from amyloid positive to negative in BAN2401 10mg/kg biweekly in Phase II study*3: APOE4 status, clinical stage (MCI due to AD and mild AD), concomitant AD medication *4: Cerebrospinal fluid *5: Alzheimer’s Disease Composite ScoreBAN2401*

Next Steps

Initiated contact with major health authorities
Initiated Study 201 Open-label extension (OLE)
to collect further clinical data
Initiated active planning on additional
confirmatory study with authorities
11* Investigational. Co-development with Biogen. Licensed in from BioArctic.

Aducanumab*1

Clinical studies are steadily ongoing
Long-term extension (LTE) Phase Ib study(Additional analyses at 36 months and 48 months)*2

Amyloid plaque levels as measured by PET continued to decrease in a dose- and timedependent manner in patients from the titration cohort at 36 months andfixed-dose cohorts at 48 months
Analyses of exploratory clinical endpoints CDR-SB*3 and MMSE*4 suggest a continued benefit
on the rate of clinical decline over 36 months and 48 months, respectively
The results were consistent with previous interim analysis,
there were no changes to the risk-benefit profile of aducanumab

Phase III studies (ENGAGE and EMERGE)
Achieved full-enrollment in July 201812

*1: Investigational. Co-development with Biogen*2: Presented at 11th Clinical Trials on Alzheimer’s Disease (CTAD) held in Barcelona, Spain from October 24 to October 27, 2018
*3: Clinical Dementia Rating–Sum of Boxes*4: Mini-Mental State Examination

Elenbecestat•

Elenbecestat has relative selectivity to BACE1 (BACE1/BACE2=0.28)*2-•-

Dose decision guided by APP A673T (Icelandic mutation) variant that reduces A-beta production by ~40%;
carriers of the variant show ~75% lower risk of AD*4,5
The study results support its exploratory endpoints by showing significant difference of brain A-beta andtrend of less decline on clinical symptoms.
Initial impact on cognitive function seen in other BACE inhibitors’ clinical studies has also not been
observed

Selected optimal dose setting for Phase III studies (MISSION AD) by confirming
balance of expected effect to inhibit A-beta production and safety-

13

Substrate selectivity of BACE1/2 may be important for neuronal/synaptic maintenance and brain immunity*3
Preclinical studies did not demonstrate serious adverse reactions, such as synaptic dysfunction,
hypopigmentation, and motor dysfunction

Study 202 investigated a range of doses and focused on selecting a dose
(50mg/day) with >50% reduction in CSF A-beta, but not higher than 75%
-

•

*1

No signals have been observed for safety concerns from generated data
(Satisfied safety evaluations for MISSION AD by Data Safety Monitoring Board)
MISSION AD is ongoing, aiming for full enrollment completion in FY2018*1: Investigational. Co-development with Biogen.
*3: Voytyuk et al. Life Science Alliance 1.; (2018)*2: Internal Eisai Data, Unit: Ki inhibition constant (Measurement for affinity of enzyme inhibitor)*4: Jonsson, T. et al. Nature (2012). 488; 96-99.; *5: Maloney, J. A. et al. (2014) J Biol Chem 289; 30990-31000.

Robust Progress of Neurology Pipeline Based on Holistic Approach
Major pipeline projects

Phase I

including projects under preparation

including projects under preparation

Phase II

Phase III and beyond

E2814 Anti-tau antibody

E2027 PDE9 inhibitor

elenbecestat*1 BACE inhibitor

Dementia with Lewy bodies
Phase II/III ongoing

Early AD
Topline results anticipated in FY2020

Alzheimer’s disease, dementia
Under preparation for Phase I

including projects under preparation

aducanumab*1 Anti-Aβ antibody

Dementia

Early ADaducanumab
Achieved full-enrollment in July 2018*2

BAN2401*1,2
Anti-Aβ protofibrils antibody
Early AD
Under preparation for an
additional confirmatory study

lemborexant*3

Sleep - Wake

Dual orexin receptor antagonist
Irregular sleep-wake rhythm disorder(ISWRD) associated with AD/dementia
Obtained topline results in FY2018

E2730

Epilepsy

Synaptic functional modulator with novel
MOA
Epilepsy and other neurological disorders

E2082
Next-generation AMPA receptor
antagonist
Epilepsy and other neurological disorders

All projects are investigational *1: Co-development with Biogen *2: Licensed in from BioArctic *3: Co-development with Purdue Pharma

14

lemborexant*3
Dual orexin receptor antagonist
Insomnia disorder
Submission anticipated in FY2018

Fycompa AMPA receptor antagonist
Pediatric indication
US: Approved in September 2018
Japan/EU: Submission anticipated in FY2018
Partial epilepsy in China
Submission accepted in October 2018
Monotherapy in Japan
Submission anticipated in FY2018
Lennox-Gastaut syndromeOncology(Mainly LENVIMA In Collaboration withMerck & Co., Inc., Kenilworth, N.J., U.S.A.)

15

LENVIMAThe first therapy to be approved for the front-line treatment of
hepatocellular carcinoma in approximately 10 years

Simultaneous submissions and approvals for hepatocellular carcinoma
in Japan, US, Europe, China, and Asia
US
Japan
Submitted: June 23, 2017
Approved: March 23, 2018
Examination period: 273 days

China

Submitted: October 30, 2017
Submitted: July 24, 2017
Approved: September 4, 2018
Approved: August 15, 2018
Examination period: 387 days Examination period: 309 days

EuropeSouth Korea

Submitted: July 24, 2017
Submitted: March 6, 2018
Approved: August 20, 2018
Approved: August 29, 2018
Examination period: 392 days Examination period: 177 days

September 19, 2018: Received approval in Australia
Submissions under review in Canada, Switzerland, Russia, Israel, Taiwan, Hong Kong,
the Philippines, Brazil, Argentina, and Colombia
16

LENVIMA

R&D collaboration withMerck & Co., Inc., Kenilworth, N.J., U.S.A.
Aim to initiate clinical studies for all potential new indications by 1H FY2019*

Thyroid cancer

1L

Renal cell carcinoma

2L

1L

Hepatocellular carcinoma

1L

1L

Endometrial carcinoma
Melanoma

Approved

1L

Non-small cell lung cancer 1L
Head and neck cancer

1L

Monotherapy
Combination witheverolimus

2L

1L
Non-squamous cell
carcinoma
Combination withchemotherapy

Breakthrough Therapy
designation from FDA

Combination with
KEYTRUDA®

2L
1L

PD-L1 positive

2L

2L

Bladder cancer

1L
Basket trial targeting multiple cancer types(Planning in breast cancer, stomach cancer, ovarian cancer, colon cancer, brain tumor, bile duct cancer, and others)
17*All projects are investigational except for the projects mentioned as “approved”. 1L: First line, 2L: Second line. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.,
Kenilworth, N.J., U.S.A. * Potential new indications that are planned to be filed based on the clinical studies under the strategic collaboration with MSD ONCOLOGY HOLDINGS LTD.,an affiliate of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

Microsatellite instability (MSI) status PD-L1 status■ MSI-high+ POS
Complete■ Microsatellite stable- NEG
response■ Unknown○ Unknown in 3 patients*2

Tumor diameter change rate (%)

Tumor diameter change rate (%)

Combination Therapy of LENVIMA + KEYTRUDA®
Potentially Expand Contribution to Patients*1
Endometrial carcinoma

Tumor response was observed
regardless of PD-L1 and MSI status

PD-L1+: 40.0%
PD-L1 -: 46.7%
Unknown 13.3%

Breakthrough therapy designation*3 granted in July 2018

Breakthrough therapy designation granted in December 2017

*ASCO 2018 Abstract No. 5596. The most common TRAEs (any grade) were hypertension, fatigue,
diarrhea, hypothyroidism, decreased appetite, nausea and stomatitis.

*ASCO 2018 Abstract No. 4560. The most common AEs (any grade) were diarrhea, fatigue, hypothyroidism,
stomatitis and nausea.

No prior treatment history 9.1%
With prior treatment history 90.9%

HPV*4 infection status
POS: 27.3%, NEG: 31.8%
Unknown: 40.9%

Hepatocellular carcinoma

response Tumor response was observedin most patients
 Confirmed tumor shrinkage
regardless of HPV infection status*ASCO 2018 Abstract No. 6016. The most common TRAEs (any grade) were fatigue, hypertension,
diarrhea, decreased appetite, oropharyngeal pain and stomatitis.

Tumor diameter change rate (%)

Tumor diameter change rate (%)

No prior treatment history 40%
With prior treatment history 60%

Tumor response was observed regardlessof PD-L1 status or prior treatment history

Head and neck carcinoma Complete

18

Renal cell carcinoma

With prior sorafenib treatment history 13.3%

Complete response■ Hep B virus ■ Hep C virus■ Alcoholic ■ Unknown ■ Other

Tumor response was observed
regardless of cause of carcinogenesis*ASCO 2018 Abstract No. 4076. The most common TEAEs (any grade) were decreased appetite, hypertension,
diarrhea and fatigue.

All projects are investigational. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A. Projects for LENVIMA are under joint development with Merck & Co., Inc., Kenilworth, N.J., U.S.A.
*1: Presented at ASCO 2018 annual meeting held in Chicago, US, from June 1 to June 5, 2018 *2: As assessed by independent imaging review *3: For the indication of lenvatinib in combination with pembrolizumab for the treatment of patients with advanced and/or
metastatic non-MSI-H/pMMR endometrial carcinoma who have progressed following prior therapy *4: human papillomavirus

LENVIMA

Commercial and medical collaboration with Merck & Co., Inc., Kenilworth, N.J., U.S.A.

Plan to initiate collaboration in major markets within FY2018

Japan

TaiwanSouth Korea

China

Germany

AustriaUK*1

US
June 2018

19

Renal cell
carcinoma*2

Sales
force

January
2019

MedicalOctober
2018

October
2018

November
2018

OctoberDecember
2018

Digitalmarketing

October
2018

Evaluation Evaluation Evaluation
Under
Under
Under
ongoingongoingongoing consideration consideration preparation

January
2019

January
2019

January
2019

November November
2018
2018

October
2018

November
2018

August 2018
Hepatocellular*3
carcinoma

October
2018

November
2018

October
2018

October2018

Merck & Co., Inc., Kenilworth, N.J., U.S.A., known as MSD outside of the United States and Canada*1: Timeline shown in the table includes target and schedule under consideration *2: Approved for 2nd line in combination with everolimus*3: Approved for 1st line unresectable hepatocellular carcinoma

Rich Pipeline Aiming for a Cure for Cancer throughTumor Microenvironment, Cancer Evolution and Precision Medicine
Major pipeline projects

Tumor
Microenvironment

Phase I

Phase IILENVIMALENVIMA

Combination with KEYTRUDA®
Hepatocellular carcinoma (HCC)

MORAb-202
ADC
Triple-negative breast cancer

E7130*1
Halichondrin analogue
Solid tumors

H3B-6545
ESR1 inhibitor
Breast cancer (Phase I/II)

Cancer
Evolution

E7386*2
CBP/Beta-catenin inhibitor
Solid tumors

Combination with
KEYTRUDA®
Endometrial carcinoma,
renal cell carcinoma (RCC),
melanoma, head and necksquamous cell carcinoma,
urothelial carcinoma,
non-small cell carcinoma(Phase I/II)

HalavenPhase IIILENVIMA
Combination with
KEYTRUDA® or everolimus
RCC 1st line

LENVIMA
Combination with
KEYTRUDA®
Endometrial carcinoma
2nd line

Combination with KEYTRUDA®
Triple-negative breast cancer(Phase I/II)

H3B-8800
SF3B1 modulator
Hematological malignancies

E7090

Precision
Medicine
20

FGFR1,2,3 inhibitor
Solid tumors

H3B-6527
FGFR4 inhibitor
HCC

tazemetostat

E7438*3
EZH2 inhibitor
B cell non-Hodgkin lymphoma

All projects are investigational. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.
Projects for LENVIMA are under joint development with Merck & Co., Inc., Kenilworth, N.J., U.S.A. *1: Compound co-created with Harvard University *2: Under development in collaboration with PRISM BioLab *3: Under development incollaboration between Epizyme Inc. and Eisai. Eisai retains responsibility for development and commercialization within Japan