(Fiscal Year Ending March 31, 2019) Financial Results ... · Q2 FY2018 (Fiscal Year Ending March...

Q2 FY2018 (Fiscal Year Ending March 31, 2019)

Financial Results Presentation

Eisai Co., Ltd. November 1, 2018

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 with the rules set by Tokyo Stock Exchange.

Materials and information provided during this presentation may contain so-called “forward-looking statements.” These statements are based on current expectations, forecasts and assumptions that are subject to risks and uncertainties that could cause actual outcomes and results to differ 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 the statements 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).

1

(Billions of yen, %)

2

Q2 FY2018 Consolidated Statement of Income (IFRS) Achieved increase in revenue/profit and

proactive investment in R&D through partnership model

Q2 FY2018 average exchange rates: 1 USD: 110.26 yen (-0.7% YoY), 1 EUR: 129.84 yen (+2.8% YoY), 1 GBP: 146.91 yen (+2.3% YoY), 1 RMB: 16.74 yen (+1.9% YoY) *1: Free cash flow = (Net cash from operating activities) – (Capital expenditures (cash basis)) (Note) Expenditures from purchases of financial assets and proceeds from sale and redemption of financial assets are

included in the formula used to calculate capital expenditures. *2: (Net DER)=("Interest-bearing debt" ("Bonds and borrowings") - "Cash and cash equivalents" - "Time deposits exceeding three months, etc.“ - “Investment securities held by the parent company") / "Equity attributable

to owners of the parent"

April-September 2017 April-September 2018

Results % Results % YoY

Revenue 285.1 100.0 310.1 100.0 109 Cost of Sales 102.2 35.8 92.0 29.7 90 Gross profit 182.9 64.2 218.1 70.3 119 R&D expenses 66.1 23.2 65.0 21.0 98 SG&A expenses 89.5 31.4 104.8 33.8 117 Other income & expenses 0.4 0.1 0.0 0.0 12 Operating profit 27.7 9.7 48.4 15.6 174 Profit for the period 20.4 7.1 36.3 11.7 178 Profit for the period (Attributable to owners of the parent) 18.8 6.6 32.7 10.5 174

ROE (%) 6.4 10.7

End of March 2018 End of September 2018

Net DER*2 -0.27 -0.31

Free cash flows*1 3.8 45.4

Interim dividends (yen) 70 70

285.1

310.1

2,500

2,700

2,900

3,100

3,300

2017年

4-9月

売上収益

グローバル

ブランドの拡大

日本事業中国・アジアレンビマ

肝細胞がん

承認

マイルストン

Aloxiの減収その他 2018年

4-9月

売上収益

+5.8

+22.2

+1.8

+8.4

+25.1B yen YoY

+6.8

3

*1

-19.9

<Major factor for increase> Divesture of Prialt in Q1

(Billions of yen)

Breakdown of Revenue Migration Achieved increase in revenue through growth of global brands,

business in Japan, China and Asia, as well as receipt of milestone payments

290.0

330.0

270.0

310.0

250.0

* Figures shown in breakdown are approximate. *1: Revenue of Lenvima, Halaven, Fycompa and BELVIQ, excluding revenue of Japan business *2: Revenue of China and Asia and Latin America region, excluding revenue of global brands *3: Hepatocellular carcinoma

April-September 2017

Revenue


Revenue

Global brands*1 Japan business

China and Asia business*2

Decrease in Aloxi revenue

Others Milestone payments for LENVIMA’s

HCC*3 indication approval

<Major factors for increase> Growth of new products Return of marketing rights for Lipacreon in Q1 <Major factor for decrease> Drug price revision in Japan

27.7

48.4

0

200

400

600

2017年

4-9月

営業利益

グローバル

ブランドの

拡大

日本事業中国・アジア

の拡大

レンビマ

肝細胞がん

承認

マイルストン

Aloxiの

減益

その他の

増減

2018年

4-9月

営業利益

+4.4 +4.4

-10.0 +22.2

*3

4

+20.6B yen YoY

-7.7

*1

*2 *3

66.1 65.0

8.4 24.3

74.5

89.3

April-September2017

April-September2018

Partners' share of R&DcostR&D cost

<Major factors for increase> Growth of new products Return of marketing rights for Lipacreon in Q1 <Major factor for decrease> Drug price revision in Japan

<Major factors for increase> Divesture of Prialt in Q1 Decrease in R&D expenses +1.1B yen <Major factor for decrease> Increase due to profit sharing associated with strategic partnership

with Merck & Co., Inc., Kenilworth, N.J., U.S.A. -7.9B yen * Figures shown in breakdown are approximate *1: Operating profit from Lenvima, Halaven, Fycompa and BELVIQ, excluding profit of Japan business *2: Operating profit from business in China and Asia and Latin America, excluding profit of global brands *3: Hepatocellular carcinoma *4: Operating profit of Aloxi

(Billions of yen)


Operating profit

Global brands*1

Japan business

China and Asia

business*2

Decrease in Aloxi profit*4

Breakdown of Operating Profit Migration Achieved increase in revenue through growth of global brands,

business in Japan, China and Asia as well as receipt of milestone payments Proactive investment in R&D by partnership models

20.0

40.0

60.0

Others April-September 2018

Operating profit

Milestone payments for LENVIMA’s

HCC*3 indication approval

(Reference) R&D expenses inclusive of partners’ share of costs (Billions of yen)

Approved in US for partial-onset seizures in pediatric patients age 4 and older in September 2018; plan to submit in Japan and EU within FY2018

Submitted for combination therapy for partial-onset seizures in China in October 2018

Aim to submit for monotherapy in partial-onset seizures in Japan in Q4 FY2018

New data being prepared on prevention and remission of T2DM*4 from long-term Cardiovascular Outcomes Trial published in The Lancet*5

Approved for hepatocellular carcinoma indication globally*1

Initiated co-commercialization with Merck & Co., Inc., Kenilworth, N.J., U.S.A., in the U.S. in June 2018, and commenced joint medical and marketing activities with MSD*2 in Japan in October 2018*3

5

1H FY2017 1H FY20182.6 2.1

6.6 9.2

20.2 20.4

14.7

24.5

LENVIMAHalavenFycompaBELVIQ

44.1B yen

56.2B yen 127% YoY

*1: Approved for unresectable HCC in Japan in March and in China in September 2018; 1st line unresectable HCC in US and South Korea, 1st line advanced or unresectable HCC in EU in August 2018 *2: Merck & Co., Inc., Kenilworth, N.J., U.S.A., known as MSD outside of the United States and Canada *3: Plan to commence collaboration on commercialization activities via sales force in January 2019. *4: Type-2 diabetes mellitus *5: First published in 1823 and with a history spanning over 190 years, The Lancet is an influential medical journal that is highly regarded worldwide.

Revenue of 4 global brands (Billions of yen)

Topics for 1H FY2018

New Suzhou Plant

Production capacity/year Formulations: approx. 3 billion tablets Packaging: approx. 5 billion tablets Site area: approx. 134,000 m2

Opening ceremony for new Suzhou Plant anticipated on

November 7, 2018 in China

6

Dementia (Mainly from the presentation at CTAD*1)

*1: Presented at 11th Clinical Trials on Alzheimer’s Disease (CTAD) held in Barcelona, Spain from October 24 to October 27, 2018 *2: Investigational. Co-development with Biogen. *3: Licensed in from BioArctic. *4: Investigational. Co-development with Purdue Pharma

BAN2401*2,3

Study 201 elenbecestat*2 Study 202 lemborexant*4 Study 202

aducanumab*2 Long-term extension (LTE) Phase Ib study

BAN2401*1

Adaptive Designs

7

• Study 201 satisfies the key principles of FDA Draft Guidance for Adaptive Designs, issued in September 2018*2

• Bayesian response-adaptive design is a legitimate statistical method and enables early decision making and early evaluation for treatment effect by randomizing more patients to treatment groups with higher response based on interim analysis

• The study maintained integrity and allowed interpretability by using pre-defined design, with limited access of comparative interim results (only to external experts) and well controlled Type I error*3 contributing to reproducible treatment effects

• Conventional (pre-specified) statistical analysis was used to assess the observed data at the end of the double-blinded treatment period of 18 months

Study 201 is a placebo-controlled, double-blind, parallel-group, randomized study in 856 patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild Alzheimer’s dementia (collectively known as early Alzheimer’s disease) with confirmed amyloid pathology in the brain. Patients were randomized to five dose regimens, 2.5 mg/kg bi-weekly, 5 mg/kg monthly, 5 mg/kg bi-weekly, 10 mg/kg monthly and 10 mg/kg bi-weekly, or placebo. *1: Investigational. Co-development with Biogen. Licensed in from BioArctic *2: FDA Guidance (Draft): Adaptive Designs for Clinical Trials of Drugs and Biologics *3: Rejecting a true null hypothesis

*1: Investigational. Co-development with Biogen. Licensed in from BioArctic *2: Alzheimer’s Disease Composite Score *3 Clinical Dementia Rating–Sum of Boxes *4 Mini Mental State Examination *5 Alzheimer's Disease Assessment Scale-cognitive subscale

8

• ADCOMS combines data from recognized clinical outcome assessment (CDR-SB*3, MMSE*4, ADAS-Cog*5) and leverages specific items that are more likely to be impacted earlier in the disease - Incorporates all six components of

CDR-SB, plus select cognitive components of MMSE and ADAS-Cog

J Neurol Neurosurg Psychiatry. 2016 Sep; 87(9): 993–999.

Components of ADCOMS

CDR-SB (all items)

・Memory ・Orientation ・Judgement and problem solving ・Community affairs ・Home/hobbies ・Personal care

MMSE ・Orientation time ・Constructional praxis

ADAS-Cog ・Word finding difficulty ・Word recognition ・Orientation ・Delayed word recall

BAN2401*1

ADCOMS*2

9

Monomer Dimer Oligomer Protofibrils Amyloid plaque Fibril

Aβ

A-beta aggregates

BAN2401*

Profile

Amyloid

Tau

Neurodegeneration

Microtubule

Tau Phosphorylation of Tau

Neurofibrillary tangle

p-Tau Nerve damage

Pathophysiology Mechanism of action

Source: Internal Eisai data and CR Jack Jr., et al. Alzheimers Dement. 2018 Apr; 14(4): 535–562 * Investigational. Co-development with Biogen. Licensed in from BioArctic.

• BAN2401 is an antibody with a low affinity for A-beta monomers and high affinity for aggregated A-beta species (>1000x)

• Among aggregated species, BAN2401 shows preferential activity for A-beta protofibrils over fibrils (>10x)

• BAN2401 both neutralizes the large soluble aggregates and clears aggregated A-beta species from the brain via Fc-mediated phagocytosis

Neurofilament L

Neurogranin

Axonal degeneration Synaptic damage

10

Adju

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Placebo data on ADCOMS*2

Overall slope: 0.009105

APOE4 non-carriers slope: 0.008221

APOE4 carriers slope: 0.009989

Analysis visit (months)

ADCOMS [p=0.3808] comparing slopes for APOE4 carriers and non-carriers

Wor

seni

ng

*1: Investigational. Co-development with Biogen. Licensed in from BioArctic. *2: Alzheimer’s Disease Composite Score *3: Liu, et. al., Nat Rev Neurol. 2013 Feb; 9(2): 106–118 *4: Steenland, et. al., J Alzheimer Dis. 2018 63(4) 1383-1393

BAN2401*1

APOE4 status (1)

Overall APOE4 non-carriers APOE4 carriers

• Proportion of APOE4 carriers is 71% in placebo arm and is consistent with the general ratio reported in A-beta positive early AD patients

• Clinical decline for APOE4 carrier and non-carrier placebo groups aligned around that of the overall placebo group and were not statistically different from each other

• APOE4 status is a risk factor for age of onset of disease*3, but has limited effect on disease progression at this stage of disease*4

N with data Placebo overall 238 226 216 201 187 172 160 APOE4 carriers 168 161 150 141 134 124 113 APOE4 non-carriers 70 65 66 60 53 48 47

11

• APOE4 status was not a contributing factor in driving disease progression; however, clinical stage, concomitant AD medication, and baseline ADCOMS were

• Impact of key factors on disease progression as measured by ADCOMS*2 by APOE4 status, clinical stage, with/without concomitant AD treatment with protocol-specified conventional statistical analysis, Mixed Model Repeated Measures (MMRM) models

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

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Contributing factors have p<0.05 Not

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p=0.68

p=<0.01 p=<0.01 p=0.03

Ongoing AD meds Clinical stage APOE4 status

Baseline ADCOMS

BAN2401*1

APOE4 status (2)

*1: Investigational. Co-development with Biogen. Licensed in from BioArctic. *2: Alzheimer’s Disease Composite Score Analyses were based on protocol-specified Mixed Model Repeated Measures (MMRM) models.

Impact of key factors as measured by ADCOMS

0.00

0.20

APOE4 carriers

Overall

N with 18 month data Number of subjects

included in the analysis 160 79 113 10 47 69

N randomized N with 18 months data 247 161 175 48 72 113

Wor

seni

ng

Placebo Highest dose arm

APOE4 non-carriers

12

vs placebo

less decline(%): 30% 63% 7%

BAN2401*1

APOE4 status (3)

Data of highest dose arm (10mg/kg bi-weekly)

on ADCOMS*2 • 30% less decline observed in highest dose arm,

63% in APOE4 carriers and 7% in APOE4 non-carriers. Treatment effect was not thought to be due to an imbalance in subject allocation by APOE4 status (APOE4 carrier: 48 subjects, APOE4 non-carrier: 113 subjects). Conversely, the imbalance may have underestimated the overall BAN2401 treatment effect

Cha

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• Pooling the highest dose arm and 10 mg/kg monthly doses corrects APOE4 imbalance and results in less decline on ADCOMS vs. placebo at 18 months of:

‒ 21% overall (n*3=414) ‒ 25% for APOE4 carriers (n*3=273) ‒ 6% for APOE4 non-carriers (n*3=141)

• PK modeling suggests that Cavg is a key driver of dose response between 10 mg/kg bi-weekly and monthly. This analysis supported the results that highest dose arm showed higher treatment effect than 10mg/kg monthly arm

Analyses were based on protocol-specified Mixed Model Repeated Measures (MMRM) models with longitudinal assessment of data for all subjects

0.00

0.20

*1: Investigational. Co-development with Biogen. Licensed in from BioArctic. *2: Alzheimer’s Disease Composite Score *3: n = number of subjects randomized to 10 mg/kg bi-weekly and 10 mg/kg monthly dose groups combined

18 months data for sub-group study for APOE4 carrier is not analyzed with 10 subjects at 18 months

The 18 months analysis was conducted based on all subjects’ data which has after administration data out

of 48 randomized subjects, utilizing MMRM

-0.40

-0.35

-0.30

-0.25

-0.20

-0.15

-0.10

-0.05

0.00

0.05

0.10

13

BAN2401*1

APOE4 status (4)

APOE4 carriers

APOE4 non-

carriers Overall

N with 18 mo. PET data 88 37 65 4 23 33 64 23 24 14 38 16 50 21

N enrolled in PET sub-study 98 44 72 9 26 35 72 27 26 17 44 20 54 24

MCI due to AD Mild AD

With concom. AD meds

Without concom. AD meds

Placebo Highest dose arm*2

ADCOMS % less decline vs. placebo: 46% 72% 29% 52% 52% 52% 37%

• Amyloid clearance in the brain and improvement in clinical symptom decline on ADCOMS*3 were consistent across subgroups

• Clinically meaningful improvement in clinical symptom decline on ADCOMS was observed in APOE4 non-carriers arm A

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Amyloid PET sub-study data (highest dose arm*2) based on the reference region of whole cerebellum

Analyses for the overall population were based on protocol-specified Mixed Model Repeated Measures (MMRM) models with factors of treatment, visit, clinical stage, the presence of ongoing AD treatment at baseline, APOE ε4 status, region, treatment-by-visit interaction and baseline value. The corresponding stratification factor was removed in the subgroup analyses. *1: Investigational. Co-development with Biogen. Licensed in from BioArctic. *2: 10 mg/kg bi-weekly *3: Alzheimer’s Disease Composite Score

14

APOE4 status is not a contributing factor for treatment effect

evaluation of BAN2401

The effect to slow cognitive decline observed in the highest

dose arm*2 is thought to be the treatment effect of BAN2401

BAN2401*1 APOE4 status (summary)

*1: Investigational. Co-development with Biogen. Licensed in from BioArctic. *2: 10mg/kg bi-weekly

BAN2401*1 Suggested disease modifying effect (1)

• Correlation of amyloid clearance in the brain and improvement in clinical symptom decline with BAN2401 administration was observed (rp=0.838)

Correlation of ADCOMS*2 and PET SUVr

AMYLOID CLEARANCE

rp = 0.838

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DC

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Adjusted mean difference from placebo group in PET SUVr*3

CLI

NIC

AL IM

PRO

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ENT

10 mg/kg bi-weekly

10 mg/kg monthly

5 mg/kg bi-weekly

5 mg/kg monthly

2.5 mg/kg bi-weekly

N with 18 months PET data 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 protocol-specified 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) 15

16

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

• Significant treatment effect for disease progression of AD during treatment period is observed in BAN2401 arm, and also suggests sustainable treatment effect and potentially expanded treatment effect over time

-0.20

-0.15

-0.10

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Placebo 10mg/kg bi-weekly (N=161)

Slope = 0.0060 P<0.001

傾き = 0.0083

WO

RSE

NIN

G

months

Slope analysis of ADCOMS*2

*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 *3: 10 mg/kg bi-weekly

Slope = 0.0083


17

Placebo Combined 10 mg/kg*3

+156

+75

Reduction of phospho-Tau (p-Tau)

Slowing increase in neurofilament light chain (NfL)

-58

+0.01

-12

48% Observed difference

vs. placebo

Reduction of neurogranin • 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 from baseline) over 18 months

• 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

• 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 to

placebo over 18 months

*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

Med

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+13.5

Placebo

Placebo

Combined 10 mg/kg*3

Combined 10 mg/kg*3


N with 18 mo. data 16 23 Interquartile range (Q1, Q3) (-91, 32) (-97, 8)

N with 18 mo. data 16 23 Interquartile range (Q1, Q3) (-2, 12) (-20, 1)

N with 18 mo. data 16 23 Interquartile range (Q1, Q3) (92, 195) (16, 188)

CSF*2 biomarker data

18

Amyloid➡Tau➡Neurodegeneration Amyloid Tau

Neuro-degeneration

• Significant amyloid clearance confirmed through PET overall

• Over 80% of subjects at highest dose converted from positive to negative confirmed through amyloid PET*2

• Amyloid PET data significant across subgroups*3

• CSF*4 biomarker that indicates improvement of pathophysiology

- Inhibit nerve damage

downstream of Tau pathway (Reduction of p-Tau)

• CSF biomarker that indicates improvement of neurodegeneration

- Protect synapse (Reduction of neurogranin)

- Inhibition of axonal degeneration (Slow to increase of NfL)

Clinical outcome • Observed effect to slow cognitive decline in each evaluation items in highest dose arm 30% less cognitive decline in ADCOMS*5

• Observed less cognitive decline across subgroups*3

•Expansion of treatment effect is observed for the entire treatment period

BAN2401*1

Suggested treatment effect on early AD

*1: Investigational. Co-development with Biogen, Licensed in from BioArctic *2: 81% converted from amyloid positive to negative vs. placebo 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

19

Disease modifying agent will help reduce the cognitive decline by

potentially clearing A-beta in the brain, which is believed to be a factor in

the development of Alzheimer’s disease

Observed effect to reduce A-beta aggregates in the brain along with

improvement of CSF biomarker, and slow clinical symptom decline

suggesting potential disease modifying effect of BAN2401

BAN2401* Suggested disease modifying effect (summary)

* Investigational. Co-development with Biogen. Licensed in from BioArctic.

BAN2401*1 Initiated contact with major health authorities

*1:Investigational. Co-development with Biogen. Licensed in from BioArctic. *2: European Medicines Agency *3: Pharmaceuticals and Medical Devices Agency in Japan

• Held productive and collaborative meeting with FDA in October 2018

• Additional interactions clearly outlined by FDA to review Study 201 data in depth

U.S.

EU

Japan Meeting with PMDA*3 is planned in December 2018

20

Initiated Study 201 Open-label extension (OLE) to collect further clinical data

Initiated active planning on additional confirmatory study with authorities

• Held productive and collaborative meeting with EMA*2 in October 2018

• An advice on future development plan to be received

Elenbecestat*1 Profile

*1: Investigational. Co-development with Biogen. *2: Internal Eisai Data, Unit: Ki inhibition constant (Measurement for affinity of enzyme inhibitor) *3: Voytyuk et al. Life Science Alliance 1.; (2018) *4: Jonsson, T. et al. Nature (2012). 488; 96-99.; *5: Maloney, J. A. et al. (2014) J Biol Chem 289; 30990-31000. 21

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

- 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% - 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

Elenbecestat*1

Clinical assessment*2

*1: Investigational. Co-development with Biogen. *2: Phase 2 Study E2609-G000-202 Investigated Safety and Exploratory Efficacy in an MCI Due to AD and Mild-to-moderate AD Population *3: Centiloid scale: an average value of zero in “high certainty” amyloid negative subjects and an average of 100 in “typical” AD patients. Florbetaben and flobetapir were used as PET tracer. *4: Sample size for Elenbecestat 50 mg Total group were: baseline: N=38, 12 month: N=31, 18 month: N=29, and for placebo group were: baseline: N=16, 12 month N=14, 18 month N=12. *5: Clinical Dementia Rating-Sum of Boxes *6: Alzheimer’s Disease Composite Score *7: For subjects who were reassigned to elenbecestat 50 mg, data before and after dose reassignment were included in the analysis. 22

Significant reduction of brain A-beta

Less decline in clinical symptom*4

CDR-SB*5

Placebo

Cha

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SE

)

Dec

line Elenbecestat 50mg Total*7

• Subjects in 50 mg total group showed a significant reduction in amyloid burden at 18 months versus placebo of 24.8 units on the Centiloid scale*3

Treatment group Least squares (LS) mean Treatment

difference (LS mean difference)

p-value

elenbecestat 50mg (N=24) -12.4

-24.8 <0.001 Placebo (N=11) 12.4

Amyloid PET analysis: Mean change in Centiloid Values*3 at 18 months from baseline

• Subjects in elenbecestat 50 mg Total group showed 31% less decline compared to placebo at 18 months on CDR-SB*5

• Subjects in elenbecestat 50 mg Total group showed 33% less decline compared to placebo at 18 months on ADCOMS*6

ADCOMS*6

Dec

line

Cha

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from

ba

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e(±

SE

) Placebo

Elenbecestat 50mg Total*7

Subjects in elenbecestat 50 mg Total group showed 31% less decline compared to placebo 18 months (p = 0.55)

Subjects in elenbecestat 50 mg Total group showed 33% less decline compared to placebo (p = 0.38)

23

Elenbecestat*1

Summary • Relatively selective BACE1 inhibitor, elenbecestat is developed with careful

examination to balance risk and benefit, hoping to differentiate from other BACE inhibitors

• The study results support its exploratory endpoints by showing significant difference of brain A-beta and trend of less decline on clinical symptoms. And also, 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

• No signals have been observed for safety concerns from generated data (Satisfied safety evaluations for MISSION AD by Data Safety Monitoring Board over 6 times)

• MISSION AD*2 is ongoing, aiming for full enrollment completion in FY2018

*1: Investigational. Co-development with Biogen. Phase 2 Study E2609-G000-202 Investigated Safety and Exploratory Efficacy in an MCI Due to AD and Mild-to-moderate AD Population *2: MISSION AD (AD1 and AD2) is the name of Phase III program for elenbecestat

Aducanumab*1

Clinical studies are steadily ongoing

*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 24

The results are consistent with previous interim analyses

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 time- dependent manner in patients from the titration

cohort at 36 months and fixed-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

Phase III studies (ENGAGE and EMERGE) Achieved full-enrollment in July 2018

*1: Investigational. Co-development with Purdue Pharma. *2: Proof of concept *3: A type of circadian rhythm sleep disorder where the pattern of sleep and wakefulness that repeats itself over a 24-hour period in healthy individuals is broken down, and sleeping and waking occur instead at various times during the day and night. *4: The most common AEs in Study 202 were constipation, somnolence, arthralgia, headache and nightmare. *5: The most common AEs in Study 303 were somnolence, headache, and influenza. *6: The most common AEs in Study 304 were headache and somnolence. 25

Lemborexant*1

Confirmed POC*2 on ISWRD*3

Controlled study in older patients with active comparator, zolpidem ER Statistically significant improvement observed in sleep onset and sleep maintenance versus zolpidem ER when measured objectively with polysomnography

Obtained the primary and key secondary outcomes of the study from the six-months (placebo-controlled treatment period) Statistically significant improvement observed in subjective sleep onset latency and sleep maintenance variables of subjective sleep efficiency and subjective wake after sleep onset compared to placebo

Study 304*6

Insomnia disorder

Study 303*5

Aim to submit in Q3 FY2018 in the US, Q4 FY2018 in Japan and other countries to follow in FY2019 with the positive results of 2 Phase III studies

Irregular sleep-wake rhythm disorder (ISWRD) Study 202*4 Double-blind, placebo-controlled, parallel-group study of 62 patients with ISWRD and mild

to moderate AD Evaluation of the parameters related to circadian rhythm, nighttime sleep and daytime wake, using an actigraph over four weeks of treatment

Improvement observed on 24-hour circadian rhythm pattern with statistically significant reductions in nighttime activity compared to placebo

after four weeks of treatment at three of the four doses tested (2.5mg, 5mg, and 15mg)

26

Oncology (Mainly LENVIMA)

27

Japan • Accumulated total of 5,020 prescriptions in 7 months since HCC indication was

approved*2

• Established position by obtaining 92%*3 of thyroid cancer market share and 85%*4 of HCC market share

US • Initiated co-commercialization with Merck & Co., Inc., Kenilworth, N.J., U.S.A. in June

2018 • Approved for 1st line unresectable HCC in August 2018, accelerating patient

contribution • Top share obtained in 1st line treatment for DTC*5 market

• Approved for HCC in September 2018 (approved approx.10 months after submission with Priority Review designation)

• It is reported*6 that approx. 50% of world’s hepatic cancer patients are in China for large population with hepatitis B virus Preparing for launch of first in-house anticancer agent (scheduled on November 30)

EMEA • Approved for HCC in August 2018 • Indication expansion of renal cell carcinoma (RCC) in Germany

(brand name: Kisplyx) contributed to the growth • Aim for further growth through co-commercialization with MSD*1

(initiation planned in Q3 for HCC and RCC indications)

Asia and Latin America • Approved for hepatocellular carcinoma (HCC) in South Korea in August 2018

(Submitted in Taiwan, Hong Kong, the Philippines, Brazil, Argentina and Columbia) • Preparation accelerated aiming at initiating co-commercialization with MSD*1 in

FY2018

10.0

14.4

2.6

3.7

1.5

4.3

0.6

2.0

1H FY2017 1H FY2018

Asia and Latin America

Japan

EMEA

Americas

24.5B yen (166% YoY)

Robust Growth in All Regions Revenue of LENVIMA

(Billions of yen)

14.7B yen

*1: Merck & Co., Inc., Kenilworth, N.J., U.S.A., known as MSD outside of the United States and Canada *2: Internal data as of October 24, 2018 for the indication of HCC *3: IPSOS Healthcare Japan Tandem Oncology Monitor 1101-2018 *4: Internal estimates based on MDV analyzer of Medical Data Vision Co., Ltd. *5: Differentiated thyroid cancer *6: Source: http://gco.iarc.fr/tomorrow/home

China

US Submitted: July 24, 2017 Approved: August 15, 2018 Examination period: 387 days Japan

Submitted: June 23, 2017 Approved: March 23, 2018 Examination period: 273 days

China Submitted: October 30, 2017 Approved: September 4, 2018 Examination period: 309 days

Europe Submitted: July 24, 2017 Approved: August 20, 2018 Examination period: 392 days

South Korea Submitted: March 6, 2018 Approved: August 29, 2018 Examination period: 177 days

LENVIMA Approved in Japan for the first time in the world

Simultaneous submissions and approvals for hepatocellular carcinoma in

Japan, US, Europe, China, and Asia

September 19, 2018: Received approval in Australia

Submissions under review in Canada, Switzerland, Russia, Israel, Taiwan, Hong Kong, the Philippines, Brazil, Argentina, and Colombia

28

LENVIMA Progress in Japan

*1: Internal data as of October 24, 2018 for the indication of hepatocellular carcinoma *2: Merck & Co., Inc., Kenilworth, N.J., U.S.A., known as MSD outside of the United States and Canada *3: Plan to commence collaboration on commercialization activities via sales force in January 2019 *4: Kudo et al. Liver Cancer (2018) *5: cTACE: conventional Transcatheter arterial chemoembolization. Superselective cTACE: TACE at the subsegmental hepatic artery *6: Source: Ikeda et al. Expert Opinion Drug on Safety 2018 Online *7: IPSOS Healthcare Japan Tandem Oncology Monitor 1101-2018 *8: Internal estimates based on MDV analyzer of Medical Data Vision Co., Ltd. *9: Source: The 18th Japan Association of Molecular Targeted Therapy for HCC, abstract PL-04, SY2-3, SY2-4, P-12 29

Potential improvement on adherence for continuation of treatment by healthcare

professionals and patients realizing treatment effect, such as tumor shrinkage and lowered tumor

biomarker Tumor size reduction potentially allows further

locoregional treatment (resection, ablation, superselective cTACE*5) for these patients which

expands the options they have

Established position by achieving 92%*7 market share in thyroid cancer and 85%*8 market share in hepatocellular carcinoma (HCC)

LENVIMA demonstrating high rate of over 40% response*9 in real world data Further expansion of contribution to TACE refractory patients in advanced stage to earlier stage

Accumulated total of 5,020 prescriptions in 7 months since hepatocellular carcinoma (HCC) indication was approved*1

Initiated joint medical and marketing activities with MSD*2 in October 2018*3

14 real world evidence presentations were given at the 18th Japan Association of Molecular Targeted Therapy for HCC and showed consistency of REFLECT study results

Clinical importance of LENVIMA*4 Adverse event (AE) management optimized in Japan

Validate AEs in detail by reviewing all subjects with LENVIMA in clinical studies by KOLs at an advisory board

Findings from analysis*6

Potentially able to continue LENVIMA administration with appropriate symptom management and dose modification since hepatic encephalopathy is transient of shunt-induced cirrhosis

Potentially able to continue LENVIMA administration with short withdrawal when mild fatigue, malaise and decreased appetite appear

30

Thyroid cancer

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.

LENVIMA R&D collaboration with

Merck & Co., Inc., Kenilworth, N.J., U.S.A.

1L

Aim to initiate clinical studies for all potential new indications* by 1H FY2019

Renal cell carcinoma

Hepatocellular carcinoma

Endometrial carcinoma

Melanoma

Non-small cell lung cancer

Head and neck cancer

Bladder cancer

Basket trial targeting multiple cancer types (Planning in breast cancer, stomach cancer, ovarian cancer, colon cancer, brain tumor, bile duct cancer, and others)

1L

1L

Approved

Monotherapy

Combination with everolimus 1L

1L

1L

1L

2L

2L

1L

1L

Combination with KEYTRUDA®

2L

2L

2L

Non-squamous cell carcinoma

Combination with chemotherapy

Breakthrough Therapy designation from FDA

1L PD-L1 positive

Japan Taiwan South Korea China Germany Austria UK US

Sales force

January 2019

January 2019

January 2019

November 2018

November 2018

October 2018

November 2018

June 2018 Renal cell

carcinoma*2

August 2018 Hepatocellular

carcinoma*3

Medical October 2018

October 2018

October 2018

November 2018

October 2018

October 2018

November 2018

October-December

2018

Digital marketing

October 2018

Evaluation ongoing

Evaluation ongoing

Evaluation ongoing

Under consideration

Under consideration

Under preparation

January 2019

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

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 31

Plan to initiate collaboration in major markets within FY2018*1

FY2017 FY2018

Results % Forecast % YoY Revenue 600.1 100.0 636.5 100.0 106

Cost of sales 201.3 33.5 187.0 29.4 93 Gross profit 398.8 66.5 449.5 70.6 113

R&D expenses 139.6 23.3 147.0 23.1 105

SG&A expenses 183.9 30.6 212.7 33.4 116

Other income & expenses 1.8 0.3 0.2 0.0 11 Operating profit 77.2 12.9 90.0 14.1 117 Profit for the year 54.4 9.1 63.5 10.0 117 Profit for the year (attributable to owners of the parent) 51.8 8.6 60.5 9.5 117

EPS (yen) 181.2 211.4 117 ROE (%) 8.8 10.0 DOE (%) 7.3 7.1 Dividends per share (yen) 150 150

Forecast for FY2018 (IFRS) Upward revision of FY2018 financial forecasts

FY2017 average exchange rates: 1 USD: 110.85 yen, 1 EUR: 129.70 yen, 1 GBP: 147.03 yen, 1 RMB: 16.74 yen FY2018 average exchange rates (Q3-Q4 forecast rate): 1 USD: 113 yen, 1 EUR: 131 yen, 1 GBP: 146 yen, 1 RMB: 16.5 yen 32


33

Reference Data



Japan*1 150.9 52.9 157.7 50.8 105

Americas*2 57.5 20.2 42.8 13.8 74

China 28.0 9.8 31.8 10.3 114

EMEA*3 21.2 7.4 25.4 8.2 120

Asia and Latin America*4 21.6 7.6 24.7 8.0 114

Pharmaceutical business total 279.1 97.9 282.4 91.1 101

Others business*5 6.0 2.1 27.7 8.9 462

Consolidated revenue 285.1 100.0 310.1 100.0 109

34

Revenue by Reporting Segment

*1: Primarily Prescription Medicines, Generics, OTC and others *2: North America *3: Europe, Middle East, Africa, Russia and Oceania *4: Primarily South Korea, Taiwan, Hong Kong, India, ASEAN, Central and South America *5:“Other business” mainly includes license revenue and the pharmaceutical ingredient business of the parent company. Milestone payments of 22.2 billion yen from Merck & Co., Inc., Kenilworth, N.J., U.S.A. under the strategic collaboration for anticancer agent Lenvima were included


April-September 2017 April-September 2018 Results % % of revenue Results % % of revenue YoY

Japan*1 55.6 55.8 36.9 60.0 45.6 38.0 108 Americas*2 20.0 20.0 34.7 16.9 12.9 39.5 85

China 8.4 8.4 30.1 11.5 8.8 36.2 137 EMEA*3 7.3 7.3 34.5 11.2 8.5 44.0 153

Asia and Latin America*4 6.3 6.3 29.2 8.5 6.5 34.4 135

Pharmaceutical business total 97.6 97.8 35.0 108.1 82.2 38.3 111

Other business 2.2 2.2 36.9 23.4 17.8 84.5 1058 Reporting segment

total 99.8 100.0 35.0 131.5 100.0 42.4 132

R&D expenses and group headquarters’ management costs and other expenses*5

(72.1) (83.2)

Consolidated operating profit 27.7 9.7 48.4 15.6 174

35

Profit by Reporting Segment


*1: Primarily Prescription Medicines, Generics, OTC and others *2: North America *3: Europe, Middle East, Africa, Russia, and Oceania *4: Primarily South Korea, Taiwan, Hong Kong, India, ASEAN, Central and South America *5: Includes the amount of profits and expenses shared with partners under strategic collaborations and the amount of shared profit of 7.9 billion yen for anticancer agent Lenvima paid by Eisai to Merck & Co., Inc., Kenilworth, N.J., U.S.A.

April-September 2017 April-September 2018 Results % Results % YoY

Revenue 150.9 100.0 157.7 100.0 105 Prescription medicines 126.3 83.7 133.2 84.4 105

Humira 21.8 14.5 23.9 15.2 110 Lyrica*1 13.2 8.7 13.8 8.8 105 Aricept 13.3 8.8 9.8 6.2 74 Methycobal 9.0 5.9 7.8 4.9 87 Pariet*2,3 9.2 6.1 6.8 4.3 74 Lunesta 5.0 3.3 5.5 3.5 111 Halaven 4.7 3.1 4.9 3.1 105 Lenvima 1.5 1.0 4.3 2.8 286 Treakisym 3.5 2.3 3.7 2.3 106 Elental*2 3.4 2.3 3.3 2.1 96 Warfarin 3.2 2.1 2.8 1.8 89 Livact*2 3.1 2.1 2.6 1.6 81 Fycompa 0.7 0.5 1.4 0.9 190

Generics 13.6 9.0 12.2 7.8 90 Consumer healthcare business 11.0 7.3 12.3 7.8 112 Segment profit 55.6 36.9 60.0 38.0 108

36


Performance of Japan Pharmaceutical Business

*1: Alliance revenue *2: EA Pharma product *3: Includes sales of triple formulation Helicobacter pylori eradication packs, Rabecure Pack 400/800 and Rabefine Pack



Revenue 57.5 100.0 42.8 100.0 74 [75]

Lenvima 10.0 17.5 14.4 33.7 144 [145]

Banzel 8.0 13.9 8.5 19.8 107 [107]

Halaven 8.0 14.0 8.1 18.9 101 [102]

Fycompa 3.2 5.5 4.5 10.4 140 [141]

AcipHex 3.1 5.3 2.2 5.0 71 [71]

BELVIQ 2.0 3.4 1.9 4.5 97 [98]

Aloxi 21.5 37.3 1.5 3.6 7 [7]

Segment profit 20.0 34.7 16.9 39.5 85 [86]

37

Performance of Americas* Pharmaceutical Business

[ ] based on local currency


* North America



Revenue 28.0 100.0 31.8 100.0 114 [112]

Methycobal 10.2 36.5 10.4 32.8 102 [100]

Stronger Neo-Minophagen C and Glycyron Tablets 4.8 17.1 5.1 16.2 108 [106]

Aricept 3.5 12.6 4.9 15.3 138 [135]

Pariet 2.3 8.3 2.9 9.1 124 [122]

Segment profit 8.4 30.1 11.5 36.2 137 [134]

38


[ ] based on local currency

Performance of China Pharmaceutical Business



Revenue 21.2 100.0 25.4 100.0 120 [118]

Halaven 5.8 27.6 6.1 24.2 105 [104]

Lenvima / Kisplyx 2.6 12.3 3.7 14.6 142 [140]

Fycompa 2.4 11.5 3.0 11.6 121 [119]

Zebinix 2.6 12.4 2.8 10.9 106 [103]

Zonegran 2.2 10.2 2.0 7.9 93 [92]

Inovelon 1.1 5.2 1.1 4.5 104 [102]

Segment profit 7.3 34.5 11.2 44.0 153 [153]

39

Performance of EMEA* Pharmaceutical Business


* Europe, Middle East, Africa, Russia, and Oceania [ ] based on local currency

40

Performance of Asia and Latin America* Pharmaceutical Business


* Primarily South Korea, Taiwan, Hong Kong, India, ASEAN, Central and South America [ ] based on local currency



Revenue 21.6 100.0 24.7 100.0 114 [114]

Humira 6.0 27.8 6.6 26.9 111 [109]

Aricept 5.8 27.0 6.1 24.6 104 [102]

Lenvima 0.6 2.6 2.0 8.1 349 [354]

Pariet 2.1 9.9 1.9 7.8 90 [90]

Methycobal 1.7 7.9 1.8 7.4 108 [109]

Halaven 1.6 7.5 1.3 5.2 78 [79]

Fycompa 0.3 1.3 0.4 1.7 151 [151]

Segment profit 6.3 29.2 8.5 34.4 135 [132]

Overview of BACE Inhibitor Clinical Trial Designs

41

Study design for Phase II and beyond in the chart above is created by Eisai based on the information on ClinicalTrials.gov as of October 1, 2018. All projects are investigational *1: Merck announced APECS study to stop as of February 13, 2018 on their news release *2: Merck announced EPOCH study to stop as of February 14, 2017 on their news release *3: 60mg dose is only in Part I of study *4: Eli Lily and AstraZeneca announced AMARANTH and DAYBREAK-ALZ study to stop as of June 12, 2018 on their news release *5: Johnson & Johnson’s Janssen unit announced EARLY study to stop as of May 17, 2018 on their news release *6: Target population for this trial is participants who are asymptomatic at risk for developing AD *7: Johnson & Johnson’s Janssen unit announced their decision to stop dosing of patients in the atabecestat/JNJ-54861911 arm of the DIAN-TU trial as of July 18, 2018 on their news release *8: Target population for this trial is individuals at risk for or with a type of early onset Alzheimer's disease caused by a genetic mutation *9: CAD106 is active a-beta immunotherapy *10: Target population for this trial is people at the risk to develop clinical symptoms based on their age and genotype *11: Target population for this trial is people at risk for the onset of clinical symptoms of AD based on their age, ApoE genotype and elevated amyloid

Drug (Sponsor) Study name (Stage) Target population

(Estimated Enrollment)

Dosage Inclusion criteria (partial) Efficacy measures (Primary endpoints)

Elenbecestat (Eisai, Biogen)

MISSION AD1 Early AD 50mg

Placebo

MMSE: ≧24, CDR: 0.5 CDR memory box ≧0.5,

Amyloid positive

CDR-SB (24 months)

(Phase III) (1330) MISSION AD2 Early AD

(Phase III) (1330)

Verubecestat MK-8931

(Merck Sharp & Dohme Corp.)

APECS*1 (Phase III)

Prodromal AD (1454)

12mg Diagnosis of prodromal AD (history of subjective memory decline, does not meet criteria for dementia, Amyloid-beta

positive)

CDR-SB (104 weeks) 40mg

Placebo

EPOCH*2 (Phase II/III)

Mild to moderate AD

(2211)

12mg Diagnosis of probable AD based on both NINCDS-ADRDA

criteria and DSM-IV-TR criteria for AD, AD is of mild to moderate severity

ADAS-cog (78 weeks) ADCS-ADL (78 weeks)

40mg 60mg*3

Placebo

Lanabecestat LY3314814/

AZD3293 (Eli Lilly)

AMARANTH*4

(Phase II/III) Early AD (2202) 20mg MMSE≧20 MCI due to AD,

Probable AD (NIA-AA) ADAS-cog13 (104 week) 50mg

Placebo

DAYBREAK-ALZ*4

(Phase III) Mild AD (1899)

LY3314814 Placebo

MMSE: 20- 26, CDR: 0.5 or 1 and CDR memory box ≧0.5, Probable AD dementia (NIA-AA)

ADAS-cog13 (78 weeks)

Atabecestat JNJ-54861911

(Janssen Research & Development, LLC)

EARLY*5 (Phase II/III)

Preclinical AD*6 (1650)

5mg 25mg

Placebo

CDR: 0, Amyloid-beta positive (Participants 60-64 years age must also have 1 of PACC

(54 months) the following conditions; positive family history of dementia, APOE ɛ4 genotype, or elevated amyloid accumulation)

Atabecestat*7

JNJ-54861911 (Washington University

School of Medicine)

DIAN-TU (Phase II/III)

Preclinical AD*8

(438) 25mg

Placebo

Have an Alzheimer's disease-causing mutation or are unaware of their genetic status and have a 50% chance of

having ADAD mutation, cognitively normal or with mild cognitive impairment or mild dementia, CDR: 0-1

DIAN-TU cognitive composite score

(52, 104, 156, 208 weeks)

CNP520, CAD106*9 Generation S1 Preclinical AD*10 50mg MMSE≧24 Time to MCI due to AD or dementia due

to AD, APCC (60 months)

(Phase II/III) (1340) Placebo Homozygous APOE4 genotype

CNP-520 (Novartis)

Generation S2 (Phase II/III)

Preclinical AD*11 (2000)

15mg 50mg

Placebo

Carrier of at least one APOE4 gene if Heterozygotes, elevated brain amyloid (as measured by CSF A-beta or

amyloid PET imaging)

Overview of Anti-A-beta Antibody Clinical Trial Designs

Drug (Sponsor)

Study name (Stage)

Target population (Estimated enrollment) Dose Inclusion criteria

(partial) Efficacy measurement

(Primary endpoints)

BAN2401*1

(Eisai, Biogen) Phase II Early AD (856)

2.5mg/kg biweekly 5.0mg/kg biweekly 10mg/kg biweekly 5.0mg/kg monthly 10mg/kg monthly

Placebo

MMSE≧22, MCI due to AD, Probable AD dementia (NIA-AA), CDR: 0.5-1.0 and

CDR memory box ≧0.5, Amyloid positive

ADCOMS (12 months)

Safety

Aducanumab (BIIB037)

(Biogen, Eisai) ENGAGE (Phase III) Early AD (1605) Low dose

High dose Placebo

MCI due to AD or mild AD CDR-Global Score: 0.5

MMSE≧24, Amyloid positive

CDR-SB (78 weeks) EMERGE (Phase III) Early AD (1605)

Gantenerumab/ RG1450/

RO4909832 (Roche)

SCarlet RoAD*2

(Phase III) Prodromal AD

(799)

225mg 105mg

Placebo

MMSE≧24, Prodromal AD who are not receiving memantine or cholinesterase inhibitors

CDR-SB (104 weeks)

Marguerite RoAD*3

(Phase III) Mild AD (389) Gantenerumab

Placebo

Clinical diagnosis of probable mild AD (NINCDS/ADRDA), Amyloid-beta positive in CSF

ADAS-Cog13 (104 weeks), ADCS-ADL (104 weeks)

Graduate I (Phase III) Early AD (760) Probable AD dementia or prodromal AD (NIA-AA), Amyloid positive, MMSE≧22,

CDR-GS: 0.5 or 1.0

CDR-SB (104 weeks) Graduate II (Phase III) Early AD (760)

Crenezumab (Roche)

CREAD (Phase III) Prodromal to mild AD (813) Crenezumab

Placebo

MCI due to AD, Probable AD dementia (NIA-AA), MMSE≧22

CDR-GS 0.5 or 1.0, A-beta positive

CDR-SB (105 weeks) CREAD 2 (Phase III) Prodromal to mild AD

(750)

Solanezumab/ LY2062430

(Eli Lilly)

EXPEDITION3*4

(Phase III) Mild AD (2129) 400mg Placebo

Probable AD (NINCDS/ADRDA) Modified Hachinski Ischemia Scale≦4, MMSE: 20-26, Geriatric Depression Scale≦6, Amyloid-beta positive

ADAS-Cog14 (80 weeks)

EXPEDITION PRO*5

(Phase III) Prodromal AD (26) Solanezumab Placebo

Probable AD (IWG), MCI due to AD (NIA-AA), MoCA: 17-28, FCSRT (Picture version)<27,

Modified Hachinski Ischemia Scale: ≤4, FAQ>0, Amyloid-beta positive

ADAS-Cog14 (24 months)

A4 (Phase III) Preclinical AD*6 (1150) 400-1600mg Placebo

MMSE≧25, CDR: 0, Logical Memory II score 6-18, Amyloid positive

ADCS-PACC (240 weeks)

Gantenerumab, Solanezumab

(Washington University School of Medicine)

DIAN-TU (Phase II/III) Preclinical AD*7 (438) Gatenerumab Solenuzumab

Placebo

Have an Alzheimer's disease-causing mutation or are unaware of their genetic status and have a 50%

chance of having ADAD mutation, Cognitively normal or with mild cognitive impairment or mild dementia,

CDR: 0-1

DIAN-TU cognitive composite score (52, 104,

156, and 208 weeks)

42

Study design for Phase II and beyond in the chart above is created by Eisai based on the information on ClinicalTrials.gov as October 1, 2018. All projects are investigational *1: Licensed in from BioArctic *2: Roche announced the decision to discontinue the trial as of December 19, 2014 on their press release. FPI in open label extension study was announced at Roche Nine Months 2016 Sales Conference Call on October 20, 2016 *3: The ClinicalTrials.gov entry for this study was updated to reflect that this trial has stopped enrolling at 389 participants but is actively continuing, in October 2016. FPI in open label extension study was announced at Roche Nine Months 2016 Sales Conference Call on October 20, 2016. *4: Eli Lilly announced that solanezumab did not meet the primary endpoint in the EXPEDITION3 clinical trials as of November 23, 2016 on their press release *5: Eli Lilly announced that they made the decision to terminate the EXPEDITION-PRO study as of January 31, 2017 at 2016 Q4 earnings call *6: Target population for this trial is older individuals who may be at risk for memory loss *7: Target population for this trial is individuals at risk for or with a type of early onset Alzheimer's disease caused by a genetic mutation

Major A-beta Related AD Projects Targeting the Progression of the Disease Stage

Solanezumab (LY2062430) Phase III (EXPEDITION 3)*14

Crenezumab Phase III (CREAD)

Verubecestat MK-8931 Phase III (APECS)*3

Verubecestat MK-8931 Phase II/III (EPOCH)*4

Lanabecestat LY3314814 / AZD3293 Phase II/III (AMARANTH*6)

Gantenerumab (RG1450/RO4909832) Phase III (SCarlet RoAD)*10

Elenbecestat*1

Phase III (MISSION AD1, AD2)

Gantenerumab (RG1450/RO4909832) Phase III (Marguerite RoAD)*12

Lanabecestat LY3314814 / AZD3293 Phase III (DAYBREAK-ALZ*6)

Aducanumab*1 (BIIB037) Phase III (ENGAGE, EMERGE)

BAN2401*1,7

Phase II

Atabecestat JNJ-54861911 Phase II/III (EARLY)*2

BACE inhibitor

Anti-A-beta antibody

Solanezumab (LY2062430) Phase III (A4)*11

Crenezumab Phase III (CREAD2)*13

43

Preclinical AD Prodromal AD Mild AD Moderate AD Severe AD

Gantenerumab (RG1450/RO4909832), Solanezumab (LY2062430) Phase II/III (DIAN-TU)*8

Early AD

CNP520, CAD106*5

Phase II/III (GENERATION S1) CNP520

Phase II/III (GENERATION S2)

Gantenerumab (RG1450/RO4909832) Phase III (Graduate I&II)

Atabecestat JNJ-54861911 Phase II/III (DIAN-TU)*8,9

Solanezumab (LY2062430) Phase III (Expedition PRO)*15

Study design for Phase II and beyond in the chart above is created by Eisai based on the information on ClinicalTrials.gov as of October 1, 2018. All projects are investigational *1: Co-development with Biogen *2: Johnson & Johnson’s Janssen unit announced EARLY study to stop as of May 17, 2018 on their news release *3: Merck announced APECS study to stop as of February 13, 2018 on their news release *4: Merck announced to stop EPOCH study on February 14, 2017 on their news release *5: CAD106 is active Beta-amyloid immunotherapy *6: Eli Lily and AstraZeneca announced AMARANTH and DAYBREAK-ALZ study to stop as of June 12, 2018 on their news release *7: Licensed in from BioArctic *8: Target population for this trial is individuals at risk for or with a type of early onset Alzheimer's disease caused by a genetic mutation *9: Johnson & Johnson’s Janssen unit announced their decision to stop dosing of patients in the atabecestat/JNJ-54861911 arm of the DIAN-TU trial as of July 18, 2018 on their news release *10: Roche announced the decision to discontinue the trail on December 19, 2014 on their press release. FPI in open label extension study was announced at Roche Nine Months 2016 Sales Conference Call on October 20, 2016. *11: Target population for this trial is older individuals who may be at risk for memory loss *12: The ClinicalTrials.gov entry for this study was updated to reflect that this trial has stopped enrolling at 389 participants but is actively continuing, in October 2016. Roche announced FPI in open label extension study at Roche Nine Months 2016 Sales Conference Call on October 20, 2016 *13: AC Immune SA announced that Genentech, a member of Roche group has decided to start a second Phase 3 clinical trial CREAD2 as of February 28, 2017 on their press release. *14: Eli Lilly announced that solanezumab did not meet the primary endpoint in the EXPEDITION3 clinical trials on November 23, 2016 on their press release *15: Eli Lilly announced that they made the decision to terminate the EXPEDITION-PRO study at 2016 Q4 earnings call on January 31, 2017

Robust Progress of Neurology Pipeline Based on Holistic Approach

aducanumab*2

44

All projects are investigational *1: Co-development with Biogen *2: Licensed in from BioArctic *3: Co-development with Purdue Pharma *4: Development of treatment which is aimed at preventing repeated seizures in patients with onset of epilepsy *5: Development of treatment which is aimed at preventing onset of epilepsy or epileptic seizures *6: Development conducted by EA Pharma *7: MACE: defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. MACE+: consisting of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to unstable angina, heart failure or coronary revascularization *8: Licensed in from Meiji Seika Pharma

elenbecestat*1 Early AD

Topline results anticipated in FY2020

aducanumab*1

Early AD Achieved full-enrollment in July 2018

E2027 PDE9 inhibitor Dementia with Lewy bodies

Phase II/III ongoing

Major pipeline projects Phase III and beyond including ongoing Phase IV

Beyond Neurology

lemborexant*3

Irregular sleep-wake rhythm disorder (ISWRD) associated with AD/dementia

Obtained topline results in 2018

BAN2401*1,2

Early AD Obtained final topline analysis in July 2018

E2730 Synaptic functional modulator with

novel MOA Epilepsy and other neurological

disorders

E2082 Next-generation AMPA receptor

antagonist Epilepsy and other neurological

disorders

BELVIQ Cardiovascular outcome trial

Phase IV on MACE and MACE+*7

Obtained topline results in July 2018

lemborexant*3

Insomnia disorder Submission anticipated in Q3 FY2018

E6742 Toll-like receptor 7/8 antagonist

Autoimmune disease

E6011 Anti-fractalkine antibody

Crohn’s disease*6

Rheumatoid arthritis Analyses of Study 201 and 202 ongoing

Fycompa

Phase II including projects under preparation

Projects targeting the progress of aggressive factors accumulation, including A-beta

Projects targeting the transformation of symptoms over time

Dementia

Projects targeting epileptogenesis and ictogenesis*5

Projects targeting epileptogenesis*4

Phase I including projects under preparation

E2814 Anti-tau antibody Alzheimer’s disease, dementia

Under preparation for Phase I

Epilepsy

Monotherapy in Japan Submission anticipated in FY2018

Lennox-Gastaut syndrome

Pediatric indication US: Approved in September 2018

Japan/EU: Submission anticipated in FY2018

Partial epilepsy in China Submission accepted in October 2018

safinamide*8 Parkinson’s disease in Japan Submitted in October 2018

45

Tumor Micro-

environment

Cancer Evolution

H3B-8800

SF3B1 modulator Hematological malignancies

H3B-6545 ESR1 inhibitor

Breast cancer (Phase I/II)

Major pipeline projects

Precision Medicine

tazemetostat E7438*3

EZH2 inhibitor B cell non-Hodgkin lymphoma

E7386*2

CBP/Beta-catenin inhibitor Solid tumors

MORAb-202 ADC

Triple-negative breast cancer

E7130*1

Halichondrin analogue Solid tumors

LENVIMA Combination with

KEYTRUDA® Endometrial carcinoma,

renal cell carcinoma (RCC), melanoma, head and neck squamous cell carcinoma,

urothelial carcinoma, non-small cell carcinoma

(Phase I/II)

Halaven Combination with KEYTRUDA® Triple-negative breast cancer

(Phase I/II)

Phase I LENVIMA

Combination with KEYTRUDA®

Hepatocellular carcinoma (HCC)

Rich Pipeline Aiming for a Cure for Cancer through Tumor Microenvironment,

Cancer Evolution and Precision Medicine Phase II

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 in collaboration between Epizyme Inc. and Eisai. Eisai retains responsibility for development and commercialization within Japan


KEYTRUDA® or everolimus RCC 1st line


KEYTRUDA®

Endometrial carcinoma 2nd line

Phase III

E7090 FGFR1,2,3 inhibitor

Solid tumors

H3B-6527 FGFR4 inhibitor

HCC

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