FY2004
Financial Results＆
POC ResultsSafe Harbor Statement•

Materials and information provided during this presentation may contain“forward-looking statements” as defined in the Private Securities Litigation
Reform Act of 1995. These statements are based on current expectations,forecasts and assumptions that are subject to risks and uncertainties which
could cause actual outcomes and results to differ materially from thesestatements.

•

Risks and uncertainties include general industry and market conditions, andgeneral domestic and international economic conditions such as interest rateand currency exchange fluctuations. Risks and uncertainties particularly apply
with respect to product-related forward-looking statements. Product risks anduncertainties 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; obtaining regulatory approvals; domestic and foreign healthcare
reforms; trends toward managed care and healthcare cost containment, andgovernmental laws and regulations affecting domestic and foreign operations.

•Also, for products that are approved, there are manufacturing and marketingrisks 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 disclaims any intention or obligation to update or revise any
forward-looking statements whether as a result of new information, future eventsor otherwise.

1

2

FY2004 Consolidated Results(billions of yen, %)FY2003

FY2004

Results%

Results

Net Sales

500.2

100.0

533.0

100.0

107

32.8

Cost of Sales

97.2

19.4

98.5

18.5

101

1.3

Gross Profit

402.9

80.6

434.5

81.5

108

31.6

R&D Expenses

69.0

13.8

78.3

14.7

113

9.3

SG&A Expenses

250.9

50.2

269.4

50.5

107

18.5

Operating Income

83.1

16.6

86.8

16.3

105

3.7

Ordinary Income

83.4

16.7

89.1

16.7

107

5.7

Net Income

50.1

10.0

55.5

10.4

111

5.4

EPS (yen)

172.1

112

21.3

193.4

%

YOY (%) Inc./Dec.

Sales of Major Products
Product Name

Area

Aricept®

Total

Alzheimer’s Disease
TreatmentJapanUS$ million

EuropeAsia

Aciphex®/Pariet®

Japan

Proton Pump
Inhibitor

US

Total

$ million

EuropeAsia

FY2003Results

141.6
28.4
87.9
777
22.8
2.5
129.0
14.6
105.5
933
7.3
1.6

3

(billions of yen, %)FY2004
Results

162.9
35.1
97.6
907
27.2
2.9
132.3
19.4
104.1
968
6.8
2.1

YOY (%)

Inc./Dec.

115

21.3

123

6.7

111

9.7

117

130

120

4.5

118

0.4

103

3.3

133

4.8

99

(1.4)

104

35

92

(0.6)

133

0.5

4

Performance of Eisai Inc.
(millions of dollars, %)FY2003Results

FY2004%

Results%

Inc./Dec.

YOY(%)

Net Sales

1,734

100.0

2,001

100.0

115

267

Aricept®

777

44.8

907

45.3

117

130

Aciphex®

933

53.8

968

48.4

104

35

-

-

104

5.2

-

104

Operating Income

88

5.1

96

4.8

109

8

Net Income

53

3.1

62

3.1

115

8

301

17.4

402

20.1

133

101

Zonegran®

Operating Income(Pre-royalty deduction)

5

Consolidated Free Cash Flow(billions of yen)

Cash Flow fromOperating Activities
Results

CapitalExpenditures

Inc./Dec.

Results

Inc./Dec.

Free Cash Flow
Results

Inc./Dec.

FY2002

57.6

0.7

26.5

1.8

31.1

(1.0)

FY2003

72.7

15.1

23.8

(2.7)

48.9

17.8

FY200449.2 (23.5)

38.7

14.9

10.5 (38.4)

Active Investment to Enhance
Corporate Value- To Improve Capital Efficiency -Operating cash flow
– Earlier disposition of liability for retirement benefit allowance- Contribution to employee retirement benefit trust: ¥20.0 billion

Investing cash flow
– Strategic acquisition of products- Cash-out for acquisition of Zonegran®: ¥13.9 billion– Active investment in CAPEX worldwide- Fixed asset procurement: ¥21.7 billion
Japan: PF Building (Kashima), Formulation Facility (Misato),
Tsukuba Research Laboratories (Tsukuba), etc.
Overseas: RTP Plant (North Carolina), Eisai ResearchInstitute (Boston), Suzhou Plant (China), etc.

6

7

Status of 4 Proof Of Concept (POC) Studies
E2007
Accomplished the world’s first POC for Parkinson’s diseasein an oral AMPA receptor antagonist

E7389
Accomplished the world’s first POC for anti-cancer agent based on
microtubule growth suppression
Good response rate in breast cancer andnon-small cell lung cancer (NSCLC)

E5564
Phase IIb study for sepsis is in data analysis
and plan a meeting with FDA
Statistically significant efficacy not achieved in all-patientanalysis of CABG

E7070
Usefulness not confirmed in 4th line monotherapy study in breast cancer
Explore POCs globally as combination therapy for colorectal cancer(CRC) and breast cancer and as therapy for small cell lung cancer(SCLC), and gastric cancer in JapanE2007 Accomplished World’s First POC
for Parkinson’s Disease in an
Oral AMPA Receptor Antagonist•

In the placebo-controlled Phase IIb study for
Parkinson’s disease, demonstrated statisticallysignificant dose dependency in OFF time reduction
while showing clinically meaningful reduction in
high-dose group (per protocol)•
Well tolerated and no worsening of dyskinesia•
Pursue Phase III studies after end-of-Phase II
meeting with US and EU regulatory authorities inJune – September 2005 (studies expected to start in
3Q FY2005)•
Target NDA/MAA submission in US and EU in
FY20068

9E2007: Target Product Profile (PD)
Indication
Efficacy
SafetyAdjunctive therapy with levodopa for
Parkinson’s disease (First-in-class as AMPA
receptor antagonist)
Similar to or better than MAO-B inhibitor and
COMT inhibitor in shortening OFF time
Excellent safety profile
No worsening of dyskinesia

DrugInteractions

No major drug-drug interactions

Administration

Once a day, oral administration

Formulation

Small tablets

10

E2007: Primary Endpoint and Results
OFF time change
ITT
0Parkinsonism

OFF time

OFF time change (hours)

Dyskinesia
Therapeutic Window

Plasma L-DOPA concentration

Advanced Parkinson’s
disease with E2007

ON time

PP

-0.4
-0.31
-0.56

-0.53
-0.8

-0.68

-1.2

-1.14
-1.3
-1.39

-1.6

Placebo
0.5mg
1mg

Time
-2

-1.71

2mg

P=0.039
P=0.012(Dose dependence) (Dose dependence)E2007: Future Plans• Phase III studies in PD to be initiated after theend-of-Phase II meeting with regulatory
authorities in June-September 2005
– Two placebo-controlled Phase III studies– One Phase III study with active control(Expected 3Q FY2005)• Pursue NDA/MAA submission in US and EU
in FY2006• Complete POC for epilepsy in FY2006• Continue Phase I studies in Japan

11

12

E7389 Accomplished World’s First POC
for Microtubule Growth Suppressor•

Partial response (PR) as monotherapy in breast cancer
and NSCLC has been demonstrated in Phase II studies- PR for breast cancer (3rd line):
6 patients out of 22 in interim analysis- PR for NSCLC (2nd line):
3 patients out of 10 in interim analysis
Note: PR cases include unconfirmed cases• Showed good tolerability- Neurotoxicity was infrequent and not severe• Pursue NDA submission under Subpart H in FY2006 after
consultation with FDA for both cancer types in AugustSeptember 2005
• Initiate clinical studies for soft tissue sarcoma, prostatecancer and ovarian cancer

13E7389: Target Product Profile

Indications

Efficacy
SafetyBreast cancer: 3rd line + 2nd line + 1st line
NSCLC: 2nd line + 1st line
Soft tissue sarcoma: 2nd line + 1st line
Prostate cancer (hormone resistant): 2nd line
Ovarian cancer: 2nd line + 1st line
Also effective for taxane refractory tumors
Effective for wide variety of cancers
No severe peripheral neurotoxicity
Fewer hypersensitivity reactions (no need forpremedication with steroid or anti-histamine)

Administration

Bolus (5-minute IV)
Day 1, 8, 15, every 4 weeks

Formulation

Vials (solution)

E7389 is to be Studied withAdditional Indications
Number of new patients by cancer type and death rate (US)
Estimated number of deaths in 2005
Number of new patients120%

Pancreatic
Lung

100%
80%
60%

Ovarian

Renal

40%
20%

UterineNonHodgkin’s
lymphoma
Bladder

Colon
Breast
Prostate

0%050,000100,000
150,000
200,000
Estimated number of new patients in 2005

Source: American Cancer Society, 2005

250,000

14

E5564 - Endotoxin Antagonist Progress and Future Plan
• Coronary artery bypass graft surgery complication(CABG)– Statistically significant efficacy not achieved in all-patientanalysis but lower incidence of new organ dysfunction andmortality was demonstrated at high dose group and the effectwas most apparent in the high-risk subgroup of patients• Sepsis– Clinical phase was completed for targeted 300 patients– Data analysis to be completed in early August 2005

• Future plan
– Complete data analysis of Phase IIb sepsis study by August
2005– Plan to hold meetings with FDA in 3Q FY2005 for both sepsis
and CABG studies

15

E7070 - G1 Phase Targeting Agent Progress and Future Plan

16

• Breast cancer: Monotherapy (4th line)– Discontinue monotherapy study – interim analysis of 51 breast
cancer patients did not demonstrate PR• Future plan
– Continue clinical studies for colorectal cancer in combination withirinotecan and breast cancer with capecitabine– Continue Phase I/II study for gastric cancer in Japan– Potential further development in combination with irinotecan for
SCLC will be evaluated based on positive Phase I study results

17

POC Studies in FY2005 and FY2006• FY2005– E7070: Cell cycle G1 phase targeting agent• Colorectal cancer in combination with irinotecan and gastric cancer• Potential further development for SCLC will be evaluated based on
positive Phase I study results in combination with irinotecan– E5564: Endotoxin antagonist• Sepsis• FY2006– E2007: AMPA receptor antagonist• Epilepsy– E7389: Microtubule growth suppressor• Soft tissue sarcoma, prostate cancer and ovarian cancer– E5555: Orally active PAR-1 antagonist
Anti-thrombolitic, Small Muscle Cell (SMC) proliferation inhibitor:
Expect effective prevention of angio-stenosis, low risk of bleeding(First-in-class)• Acute coronary syndrome(including secondary prevention of Myocardinal dysfunction )18

4 POC Projects in Summary•

Achievement of POCs for E2007 and E7389
substantially increased the possibility ofdevelopment for two first-in-class products infocused areas where significant unmet medical
needs exist•

Continue to pursue rapid completion of POC
studies for E5564 and E7070

Strive for Early Achievement of
DOE 5% in FY2007(DPS: Yen)

(DOE: %)

100

5

4.8

DPS
DOE

3.7

80

60

2.4

2.5

2.6

80

56

4

3

2.0
40

29

32

36

2

23
20

1
FY2000FY2001

FY2002

FY2003

DOE = Dividends On Equity (= ROE x Dividend Payout Ratio)
DPS = Dividends Per Share

FY2004

FY2005(est.)

19

Dividend Yield
Top 20 Ranking in Japan
Company

20

Yield (%)

1

Showa Shell Sekiyu

3.42

2

Mitsui O.S.K. Line

2.86

3

Kawasaki Kisen Kaisha

2.84

4

Nippon Yusen Kaisha

2.79

5

Sumitomo Metal Industries

2.74

6

Nissan*2.68

7

Konami2.50

8Kansai Electric Power

2.39

9

NTT DoCoMo

2.38

10

Chubu Electric Power

2.38

11

Tokyo Electric Power

2.37

12

Nippon Steel*

2.35

13

Shiseido

2.30

14

Eisai

2.23

15

Heiwa Real Estate

2.16

16

Kobe Steel*

2.15

17

Sumitomo Corp.*

2.15

18

Osaka Gas

2.12

19

NSK (Nippon Seiko)

2.11

20

Oji Paper

2.09

Reference Rates
Rate (%)
10-year Japanese
Government Bond

1.284

20-year Japanese
Government Bond

1.932

Planned Dividends

Share Price as of
5/24

80 Yen3,570 Yen

Source: Nikkei
Notes: Ranking is based on companies listed
for Nikkei Average

21

Performance Forecast(billions of yen, %)FY2004
Results%

FY2005YOY

Forecast%

YOY

Net Sales

533.0

100.0

107

575.0

100.0

108

Cost of Sales

98.5

18.5

101

103.0

17.9

105

Gross Profit

434.5

81.5

108

472.0

82.1

109

R&D Expenses

78.3

14.7

113

89.0

15.5

114

SG&A Expenses

269.4

50.5

107

292.0

50.8

108

Operating Income

86.8

16.3

105

91.0

15.8

105

165.1

31.0

109

180.0

31.3

109

Net Income

55.5

10.4

111

58.0

10.1

104

EPS (yen)

193.4

112

203.0

(R&D Expenses + Operating
Income)Dividend (yen)DOE (%)
Dividend Payout Ratio (%)

56.0
3.7
29.0

Currency exchange rate: FY2004: ¥107.54/$, FY2005 (est.) ¥103/$

105
80.0
4.8
39.4

Resolution for Shareholder
Approval (1)22

THE 93RD ORDINARY GENERAL MEETING OF SHAREHOLDERS

Partial Amendments to the Articles of Incorporation
1. It is proposed that a new provision be added tostate the Company’s corporate concept andcorporate vision to be realized.
2.

The “Partial Revision to the Commercial Code for the Introduction of Electronic
Advertisements” (2004, Law No. 87), which became effective on February 1,
2005, allows companies to change the distribution of public notices fromconventional public notices to electronic ones. Accordingly, it is proposed that therelated article concerning this matter be amended.

3. It is proposed that the number of shares theCompany is authorized to issue be increased forflexible capital strategies. (700→1,100million)
4.
5.

In accordance with the change of position for convening the Board of Directors
meeting, it is proposed that the contents of the related articles be amended.
In accordance with the preceding revisions, corresponding changes shall bemade to the number of articles.

23

Corporate Concept
1. The Company’s corporate concept is to give first thought to patients and theirfamilies, and to increase the benefits that health care provides. Under thisconcept, the Company endeavors to become a human health care (hhc)company.
2. The Company’s mission is the enhancement of patient satisfaction. The
Company believes that revenues and earnings will be generated as aconsequence of the fulfillment of the mission. The Company places importanceon this positive sequence of the mission and the ensuing results.
3. Positioning compliance, the observance of legal and ethical standards as a corein all business activities, the Company strives to fulfill corporate social
responsibilities.
4. The Company’s principal stakeholders are patients, customers, shareholders
and employees. The Company seeks to foster a good relationship withstakeholders and to enhance their value through making the following efforts:– Satisfying unmet medical needs, ensuring stable supply of high quality
products, and providing useful information of safety and efficacy.
– Timely disclosure of corporate managerial information, enhancement ofcorporate value, and proactive return to shareholders.
– Ensuring stable employment, offering challenging and fulfilling duties, andproviding full opportunities for the development and enhancement of
employees’ capabilities.

24

Resolution for Shareholder Approval (2)THE 93RD ORDINARY GENERAL MEETING OF SHAREHOLDERS

Election of twelve (12) Directors
The candidates for the position of Director are as follows；
1. Haruo Naito: President and CEO
2. Yuji Naito: Senior Advisor
3. Hiromasa Nakai: Chairman
4. Tadashi Tenmyo: Director
5. Shintaro Kataoka: Senior Vice President (New candidate)
6. Stuart Meiklejohn: Partner, Sullivan & Cromwell
7. Mitsuo Minami: Pprofessor, Graduate School of Business
Administration, Bunkyo Gakuin University
8. Tadashi Kurachi: Chairman, Kanematsu Corporation
9. Naoto Nakamura: Partner, Nakamura, Tsunoda and Matsumoto
10. Ikujiro Nonaka: Professor, Graduate School of Hitotsubashi
University
11. Tadahiro Yoshida: Chairman and President, YKK Corporation
12. Yoshiyuki Kishimoto: Director of Strategy, Booz Allen Hamilton(Japan) Inc.

25

AppendicesFinancial Data
POC Studies Detail
E2007
E7389
E5564
E7070

Sales to Customers
by Geographic Area

26

(billions of yen, %)FY2003

FY2004YOY

Results%

Results

%

Japan

260.9

52.2

268.3

50.3

103

7.3

North
America

194.5

38.9

214.5

40.3

110

20.0

Europe

34.8

7.0

38.3

7.2

110

3.5

9.9

2.0

11.9

2.2

121

2.0

Overseas

239.2

47.8

264.7

49.7

111

25.5

Total

500.2

100.0

533.0

100.0

107

32.8

Asia & others(%)

Inc./Dec.

Operating Income
by Geographic Area
(Pre-royalty deduction)

FY2003

Japan
North America
EuropeAsia & others

Overseas
Sub Total

27(billions of yen, %)FY2004

Results

%

46.7
35.0
4.6
1.8
41.4
88.1

53.0
39.8
5.2
2.1
47.0
100.0

Results

40.1
44.3
4.9
2.1
51.3
91.3

%

YOY (%) Inc./Dec.

43.9

86

(6.6)

48.5

126

9.3

5.3

107

0.3

2.3

113

0.2

56.1

124

9.8

100.0

104

3.3

Elimination/
Corporate

(5.0)

(4.5)

90

0.5

Total

83.1

86.8

105

3.7

28

E2007 (AMPA-Receptor Antagonist)• Concept– Suppress neuronal damage caused by stimulation with excessive
amount of glutamate based on AMPA-receptor antagonism. Expect
good efficacy and safety profile for neurodegenerative diseases:
Parkinson’s disease, epilepsy and multiple sclerosis– Aim for first-in-class oral AMPA-receptor antagonist with excellent
ADME profile (once a day, fewer drug-drug interaction)– Equal or better OFF time reduction than current therapy as well as
dose dependency in combination with levodopa in Phase IIb studies
of Parkinson’s disease– No worsening of dyskinesias in Parkinson’s disease– Excellent safety profile• Proof of concept– Long half-life and possible once-a-day administration– Clinically meaningful OFF time reduction and statistically significant
dose dependency in Phase IIb in Parkinson’s disease– Excellent safety profile and no worsening of dyskinesias

E2007, as a Novel PD Treatment,
Has Potential toReach 1.5 Million Patients
Number of Patients (x1,000)

Number of PD patients on drug treatment
1,600

Target Patientsof E2007

1,400
Others

1,200

NMDA antagonist

1,000

MAO-B inhibitor

800

COMT inhibitor

600

Dopamine agonist

400

Levodopa

200
0US

EU (G5)

Source: Data Monitor (Total number of patients, 2005)

JP

29

30

POC for Epilepsy Initiated andPlanned for Multiple Sclerosis
Epilepsy Patients (JP, US, EU)

Generalized
Seizure2.13

MS Patients (JP, US, EU)
Primary
Progressive
Benign100
130PartialSeizure3.2

Secondary Relapsing &Progressive Remitting
250
160(millions)

Potential Patients for E2007
Source: Data Monitor, Decision Resources, Eisai(thousands)

31

E2007: Study Synopsis for Phase II– Study 204 –• Subjects– Parkinson’s disease with motorfluctuations and dyskinesias on
levodopa (maintenance dose)

Advanced Parkinson’s
disease with E2007• Endpoints– Reduction of OFF time
– Extension of ON time
– Severity of dyskinesias• Study location– Europe

Dyskinesia
Therapeutic Window– 12-week dosing– Placebo, 0.5 mg, 1 mg, 2 mg (oncea-day treatment)– Target enrollment: 180 patients (45patients/dose)

Plasma L-DOPA concentration• Study design

ON timeOFF time

Parkinsonism
TimeE2007: Phase II Results– Study 204 –• Enrollment

OFF time change– ITT: 258 (62-67/group)– Per Protocol: 166 (36-44/group)– Statistically significant dose response(p<0.025) in OFF time reduction observedin cases conforming with the protocol– Active group did not show statisticalsignificance in OFF time reduction overplacebo group, but showed clinicallymeaningful reduction at high dose (2 mg)
in protocol population– Equal or greater efficacy than current
therapy in OFF time reduction is expected• Safety and tolerability– Excellent safety profile– No worsening of dyskinesias

ITT

PP

0

OFF time change (hours)• Efficacy

32

-0.4
-0.31
-0.56

-0.53
-0.8

-0.68

-1.2

-1.14
-1.3
-1.39

-1.6

Placebo
0.5mg
1mg

-2

-1.71

2mg

P=0.039
P=0.012(Dose dependence) (Dose dependence)E7389 – Microtubule Growth
Suppressor –33• Concept– New chemical entity featuring unique mechanism of action based on microtubule
growth suppression and different from current tubulin polymerization inhibitors(taxanes, vinca alkaloids); effective against taxane-resistant cancers– Effective against wide anti-cancer spectrum– Better tolerability than current chemotherapy• Proof of concept– Basic research indicates suppression of microtubule growth and no influence on
microtubules in stable condition unlike taxanes or vinca alkaloids (paper submitted)– Pre-clinical studies showed superior anti-cancer effects in taxane sensitive andresistant cancers than that of taxanes– Phase I studies revealed PRs in multiple cancer types, including non-small celllung cancer (NSCLC), resistant to taxane therapy and has no other treatment
options– Phase II studies in 2 major cancer types, breast and NSCLS, showed many PRs
in patients resistant to combination chemotherapies including standard therapy
with taxanes– Neurotoxicity was infrequent and not severe– No hypersensitivities observed and no required pretreatment with steroid or antihistamine not required as in cases of taxane therapy

34

E7389: Study Synopsis for Phase II– Study 201–
(Breast cancer, Monotherapy)• Subjects– Breast cancer previously treated with chemotherapy, whichmust have included anthracycline and taxane• Study design– I.V. bolus on Days 1, 8, and 15 of a 28-day cycle– Dose = 1.4mg/m2– Target enrollment: 61 patients (interim analyses: 19 patients)• Endpoints– Response rate
– Safety and tolerability, duration of response, TTP, survival• Study location
– US

35

E7389: Interim Analysis for Phase II– Study 201–
(Breast cancer, Monotherapy)• Enrollment– 22 patients (all taxane resistant)• Efficacy– 6 patients with PR• 3 confirmed PR• 3 unconfirmed PR (before cycle 4)• All responses reviewed by independent assessors• Safety– Neurotoxicity was infrequent and not severe

36

E7389: Study Synopsis for Phase II– Study 202–
(NSCLC, Monotherapy)• Subjects– Advanced NSCLC, progressed during or after platinumbased doublet chemotherapy• Study design– I.V. bolus on Days 1, 8, and 15 of a 28-day cycle– Dose = 1.4mg/m2– Target enrollment: 48 patients• Endpoints– Response rate
– Safety and tolerability, duration of response, TTP, survival,
and QOL (Lung Cancer Symptom Scale)• Study location
– US

37

E7389: Interim Analysis for Phase II– Study 202–
(NSCLC, Monotherapy)• Enrollment
55 patients (all taxane resistant)
10 currently evaluable patients• Efficacy
3 PRs, 1 confirmed PR (after cycle 3) and 2 unconfirmed PRs(after cycle 2)
PRs were evaluated by independent assessors

38

E7389: Target Indications• Breast cancer– 3rd line therapy– 2nd line therapy– 1st line combination therapy• NSCLC– 2nd line therapy– 1st line combination therapy• Soft tissue sarcoma– 2nd line therapy– 1st line therapy• Hormone resistant prostate cancer– 2nd line therapy• Ovarian cancer– 2nd line therapy– 1st line combination therapy

39

E7389: Future Plans• Initiate registration study based on
discussions with FDA (end of Phase II
meeting; breast cancer and NSCLC) in
August-September 2005
• Potential Subpart H NDA filing in FY2006• Initiate clinical studies for other indications
within FY2005

40

E5564 (Endotoxin Antagonist)• Concept– World’s first endotoxin antagonist as lipid-A analog that reduce
mortality in sepsis– Reduce organ dysfunction rate and mortality after CABG surgery– Good safety profile• Proof of concept– All patients in Phase IIb of sepsis study, targeting 300 patients,
completed clinical phase; data analysis due in August 2005
– In CABG study, statistically significant efficacy was not achieved
between all-pooled active group and placebo group in new organ
dysfunction, nor in apparent dose dependency– In CABG study, lower incidence of new organ dysfunction andmortality was demonstrated in high dose group and the effect wasmost apparent in the high-risk subgroup of patients– Well tolerated at doses tested in more than 800 patients with CABG
– Independent data safety management board (DSMB) assessment
requested by FDA concluded no safety concerns in interim analysis ofsepsis study

E5564: Study Synopsis for Phase II– Study 204 – (CABG)

41• Subjects– Patients undergoing cardiopulmonary bypass for coronary
artery bypass graft and/or valve surgery• Study design– Intravenous infusion for 4 hrs starting 1 hr prior to operation– Placebo, low-dose (2 mg), mid-dose (12 mg) and high-dose(28 mg)– Target enrollment: 1,000 patients (250 patients/dose)• Endpoints– Reduction in incidence of new organ dysfunction within 14
days of surgery– Duration of organ dysfunction, length of total and organ
dysfunction-associated ICU and hospital stays, ventilation
assistance and renal dialysis days, volume of blood andblood products infused within 24 hrs of surgery, incidence of
hospital readmission, 28-day all-cause mortality, etc.

• Study location– Europe and Canada

•E5564: Summary for Phase II– Study 204 – (CABG)
Enrollment–•

Efficacy–––•

1,018 patients (evaluable: 982 patients)
Statistically significant efficacy was not achieved between allpooled active group and placebo group in new organ
dysfunction, nor apparent dose dependency
A numerically lower incidence of new organ dysfunction wasdemonstrated in the E5564 high dose (28 mg) groupcompared to placebo
At 28 days and overall, the lower mortality occurred in theE5564 high dose (28 mg) group. The effect was mostapparent in the high-risk subgroup of patients
No difference in time on artificial respirator adapter or kidney
dialysis, volume of blood transfusion within 24 hrs of surgery
or in length of ICU stay; no correlation with new organ failure

Safety and tolerability–

Confirmed good safety profile

42

43

E5564: Study Synopsis for Phase II– Study 201– (Sepsis)• Subjects– Septic patients with acute organ malfunction• Study design– Intravenous infusion up to 6 days
– Placebo, low-dose (total 45 mg), high-dose (total 105 mg)– Target enrollment: 300 patients(100 patients/dose)• Efficacy endpoints– 28-day all-cause mortality– Number of patient organ-failure free days, organ failure
scores, length of ICU and hospital stays, etc.

• Study location– US and Canada

44E5564: Status for Phase II– Study 201– (Sepsis)• Independent data safety management board (DSMB)
did not identify any safety concerns based on theinterim analysis• Enrollment (300 patients) was completed in March
2005 as well as clinical phase of all patients in April
Data analysis is ongoing• Data analysis will be completed by early August 2005

E5564: Future Plan
• Complete data analysis of Phase IIb
sepsis study by August 2005
• Plan to hold meetings with FDA for both
sepsis and CABG studies in 3Q FY2005

45

E7070 – Cell Cycle G1 Phase
Targeting Agent –• Concept– Exhibit unique anti-tumor spectrum compared to conventional anticancer drugs based on a new mechanism of action at cell cycle G1
phase where the control mechanism is most different between normal
cells and cancer cells– Synergistic effects in combination with other agents– Synergistic effects are especially obvious with down regulation of
topoisomerase II when combined with irinotecan that triggers upregulation of topoisomerase II• Proof of concept– Breast cancer 4th line monotherapy had no PR case– Continue Phase II studies for colorectal cancer (CRC)in combination
with irinotecan and for breast cancer in combination with capecitabine– Continue Phase I/II study for gastric cancer in Japan– Plan to start efficacy confirmation study for SCLC as 3PRs and 4SDsout of 9 patients reported in Phase I study for SCLC in combination
with irinotecan

46

47

E7070: Study Synopsis for Phase II– Study 211–
(Breast cancer, Monotherapy)• Subjects– Advanced metastatic breast cancer - patients previously treatedwith anthracycline, taxane, and fluoropyrimidine• Study design– Target: 232 patients• 1st stage: 30 patients, 2nd stage: 89 patients– 800mg/m2, administered once every 3 weeks• Efficacy endpoints– Response rate (1st interim analysis is intended for 30 evaluable
patients)– Duration of response, TTP, 6-month survival, safety, tolerability,
and QOL• Study location
– US

48

E7070: Interim Analysis for Phase II– Study 211–
(Breast cancer, Monotherapy)• Enrollment– 51 patients• Efficacy– PR was not demonstrated– Average number of administration cycle comes out to 2 (3weeks per cycle)

49

E7070: Study Synopsis for Phase II– Study 214–

(CRC, Phase II in combination with irinotecan)• Subjects– Metastatic colorectal cancer– Received prior therapy with 5-fluorourasil/leucovorin andoxaliplatin; no more than three previous chemotherapy regimens• Study design– Target enrollment: 40 evaluable patients– Administered on Days 1 and 8 of a 21-day cycle– Treatments (administered consecutively):• Irinotecan 125 mg/m2 IV infusion over 90 minutes• E7070 400 mg/m2 IV infusion over 40 minutes• Efficacy endpoints– Response rate
– Duration of response, TTP, 6-month survival, tolerability and safety• Study location– Europe

50

E7070: Interim Analysis for Phase II– Study 214–
(CRC, Phase II in combination with irinotecan)• Enrollment– 29 patients• Best response– Stable disease (SD)• Results of 40 evaluable patients due by September
2005E7070: Future Plans• Discontinue development as monotherapy(4th line) for breast cancer• Continue development for CRC in
combination with irinotecan and for breast
cancer in combination with capecitabine• Continue Phase I/II study for gastric cancer• Plan to start study for SCLC (some responses
recognized in the Phase I study for SCLC in
combination with irinotecan)51