11．Major R&D Pipeline(1) Neurology

Development Code: BAN2401

Generic Name: lecanemab

Product Name: Leqembi

In-license (BioArctic AB)
Injection

Indications / Drug class: Treatment for Alzheimer’s disease / anti-Aβ protofibril antibody

Description: An lgG1 antibody that targets amyloid beta (Aβ) protofibrils. Reduces the rate of disease progression and slows cognitive andfunctional decline in adults with Alzheimer’s disease (AD) through the elimination of neurotoxic Aβ protofibrils. In July 2023, lecanemab was
granted traditional approval in the United States as a treatment for AD by the U.S. Food and Drug Administration (FDA) after an application
supporting the conversion of the accelerated approval to a traditional approval based on the Phase III clinical study Clarity AD. Applications
have been submitted for use in the treatment of early AD in Japan, Europe, China, Canada, Great Britain, Australia, Switzerland, South Korea
and Israel. The applications have been designated for priority review in Japan, China and Israel. In Great Britain, lecanemab has been
designated for the Innovative Licensing and Access Pathway, which aims to reduce the time to market for innovative medicines. Developmentof subcutaneous injection formulation is underway to enhance convenience for patients. In addition, a study to determine a new dosing regimen
for maintenance treatment after removal of brain Aβ is also underway. The Phase III clinical study AHEAD 3-45 for preclinical (asymptomatic)
AD is underway in collaboration with the Alzheimer's Clinical Trials Consortium (ACTC). Joint development with Biogen Inc.
Study 301
(Clarity AD)

Early AD

Study 303
(AHEAD 3-45)

Preclinical AD
Development Code: E2007

Generic Name: perampanel

US
EU
JP
CH
Asia (SK)◎◎JP/US/EU

Product Name: Fycompa

Indications / Drug class: Antiepileptic agent / AMPA receptor antagonist

Traditional approval (July 2023)
Submission (accepted: January 2023)
Submission (January 2023)
Submission (December 2022)
Submission (June 2023)
PIII
In-house
Oral

Description: Selectively inhibits the AMPA receptor (a glutamate receptor subtype) activation by glutamate. Approved as an adjunctive therapy
for partial-onset seizures in over 75 countries including Japan, China and countries in Europe and in Asia. Approved for monotherapy in Japanand China. Also approved as an adjunctive therapy for primary generalized tonic-clonic seizures in over 70 countries including Japan, andcountries in Europe and in Asia. An oral suspension formulation has been approved in Europe and China. A fine granule formulation has been
approved in Japan. In January 2023, the commercial rights in the United States were transferred.
Injection formulation (Additional Formulation)―

JP

Submission (August 2022)

Primary generalized tonic-clonic seizures(Additional Indication)

Study 332

CH

Submission (March 2023)

Lennox-Gastaut syndrome (Additional Indication)

Study 338

JP/US/EUPIII

Development Code: E2006

Generic Name: lemborexant

Product Name: Dayvigo

In-house
Oral

Indications / Drug class: Insomnia treatment / Orexin receptor antagonist

Description: An orexin receptor antagonist that blocks the receptors involved in the regulation of sleep and wakefulness. It is expected toalleviate wakefulness, thereby facilitating faster onset and maintenance of sleep. It has been approved for the treatment of insomnia in over
15 countries including Japan, the United States and countries in Asia. In addition, development for irregular sleep-wake rhythm disorder andAlzheimer’s disease dementia is ongoing.
Insomnia disorderStudy 311

Irregular sleep-wake rhythm disorder andStudy 202
Alzheimer’s disease dementia (Additional Indication)
Development Code: E2023

CH

PIII

JP/US

PII

In-license(Arena Pharmaceuticals)

Generic Name: lorcaserin

Indications / Drug class: Treatment for Dravet syndrome / serotonin 2C receptor agonist

Oral

Description: By selectively activating serotonin 2C receptors in the brain, through the activation GABAergic inhibitory interneuron, expected tosuppress seizures of Dravet syndrome by increasing synaptic suppression from GABAergic. Although approval for the obesity indication has
been voluntarily withdrawn, due to the request from Dravet syndrome patient groups, the extended access program has been continued in the
United States, and the Phase III clinical study is underway for this indication. FDA has designated it as an orphan drug for Dravet syndrome.
Dravet syndrome

Study 304

PIII

US

JP: Japan, US: the United States, EU: Europe, CH: China, SK: South Korea, P: (Clinical trial) Phase◎：Development progress from April 2023 onwards
Reference Data [R&D Pipeline] 17

August 2, 2023 / Eisai Co., Ltd.

Development Code: E2027

In-house

Indications / Drug class: Treatment for dementia with Lewy bodies, Parkinson’s disease dementia / PDE9 inhibitor

Oral

Description: A selective phosphodiesterase (PDE) 9 inhibitor that reduces the degradation of cyclic GMP, which is critical to signal transduction
among cells. Expected to be a new treatment for dementia with Lewy bodies and Parkinson’s disease dementia by helping to maintain theconcentration of cyclic GMP in the brain.
Dementia with Lewy bodies, Parkinson’s disease dementia

Study 203US

PII

Development Code: E2814

Collaboration (University
College London)

Indications / Drug class: anti-MTBR tau antibody

Injection

Description: An anti-microtubule binding region (MTBR) tau antibody that was discovered as part of the research collaboration between Eisai
and University College London. Expected to prevent the spreading of tau seeds within the brain. Dominantly Inherited Alzheimer Network Trials
Unit (DIAN-TU) has selected E2814 as the first investigational medicine among anti-tau drugs for their DIAN-TU tau study, and Phase Ib/II study
and Phase II/III study Tau NexGen for dominantly inherited AD are underway.
AD

Tau NexGen study
Study103

JP/US/EU
US/EU

PII/III
PI/II

Development Code: E2511

In-house

Indications / Drug class: Synapse regenerant

Oral

Description: Expected to promote recovery and synaptic remodeling of damaged cholinergic neurons, and to suppress cerebral atrophy causedby neurodegeneration.
AD―

Development Code: E2025
AD―

Development Code: E2086
Narcolepsy―

Development Code: EA4017
Chemotherapy-induced peripheral neuropathy(Development conducted by EA Pharma)

―

US

PI

In-house

Injection

USPI

In-house

Oral

US

PI

In-house

Oral

JP

PI

JP: Japan, US: the United States, EU: Europe, CH: China, SK: South Korea, P: (Clinical trial) Phase◎：Development progress from April 2023 onwards
Reference Data [R&D Pipeline] 18

August 2, 2023 / Eisai Co., Ltd.

(2) Oncology
Development Code: E7080

Generic Name: lenvatinib

Product Name: Lenvima

In-house

Indications / Drug class: Anticancer agent / kinase inhibitor

Oral

Description: An orally available multiple kinase inhibitor that selectively inhibits kinase activities vascular endothelial growth factor receptors(VEGFR): VEGFR1, VEGFR2 and VEGFR3, and fibroblast growth factor receptors (FGFR): FGFR1,FGFR2, FGFR3 and FGFR4, in addition
to pathogenic angiogenesis, tumor growth and cancer progression related receptor tyrosine kinases such as the platelet derived growth factor
receptor alpha (PDGFRα), KIT, and RET. Discovered and developed in-house. As monotherapy indications, approved for use in the treatmentof thyroid cancer in over 80 countries including Japan, the United States, China and countries in Europe and in Asia. Approved for use in thetreatment of hepatocellular carcinoma (first-line) in over 80 countries including in Japan, the United States, China and countries in Europe andin Asia. Also approved for use in the treatment of thymic carcinoma in Japan. As a combination therapy with everolimus, approved for use in
the treatment of renal cell carcinoma (second-line) in over 65 countries including the United States, countries in Europe and in Asia. As a
combination therapy with pembrolizumab, approved for use in the treatment of renal cell carcinoma in over 45 countries including in Japan,
the United States, and countries in Europe and in Asia, and approved for use in the treatment of endometrial carcinoma in over 50 countries
including in Japan, the United States, and countries in Europe and in Asia, including conditional approval. The agent is marketed under the
product name Kisplyx only for renal cell carcinoma indication in Europe. Joint development with Merck & Co., Inc., Rahway, NJ, USA, throughan affiliate.
In combination with anti-PD-1 therapy pembrolizumab, joint development with Merck & Co., Inc., Rahway, NJ, USA, through an affiliate(Additional Indication)
Endometrial carcinoma / First-line

LEAP-001

JP/US/EU/CH

PIII

Non-small cell lung cancer (nonsquamous) (in combination withchemotherapy) / First-line

LEAP-006

JP/US/EU/CH

PIII

Non-small cell lung cancer / Second-line

LEAP-008

JP/US/EUPIII

Head and neck cancer / First-line

LEAP-010

JP/US/EU/CH

PIII

Hepatocellular carcinoma (in combination with transcatheter arterial
chemoembolization) / First-line

LEAP-012

JP/US/EU/CH

PIII

Esophageal carcinoma (in combination with chemotherapy) / First-line

LEAP-014

JP/US/EU/CH

PIII

Gastric cancer (in combination with chemotherapy) / First-line

LEAP-015

JP/US/EU/CH

PIII

Colorectal cancer (non MSI-H / pMMR) / Third-line

LEAP-017

US/EU

PIII

Melanoma / Second-line

LEAP-004

US/EU

PII

LEAP-005

US/EU

PII

LEAP-009

US/EU

PII

Selected solid tumors (Gastric cancer, colorectal
glioblastoma, biliary tract cancers and pancreatic cancer)
Head and neck cancer / Second-line

cancer,In combination with anticancer agent everolimus, joint development with Merck & Co., Inc., Rahway, NJ, USA, through an affiliate(Additional Indication)
Renal cell carcinoma / First-line

Study 307

JP/US/EUPIII

In combination with anti-PD-1 antibody nivolumab, joint development with Ono Pharmaceutical (Additional Indication)
Hepatocellular carcinoma

―

JP

PI

◎ Based on the independent Data Monitoring Committee recommendation, Phase III clinical study of LEAP-003 for melanoma / First-line in
the United States, Europe and China, has been decided to be discontinued and therefore was removed from this list.

JP: Japan, US: the United States, EU: Europe, CH: China, SK: South Korea, P: (Clinical trial) Phase◎：Development progress from April 2023 onwards
Reference Data [R&D Pipeline] 19

August 2, 2023 / Eisai Co., Ltd.

Development Code: E7389

Generic Name: eribulin

Product Name: Halaven

In-house

Indications / Drug class: Anticancer agent / microtubule dynamics inhibitor

Injection

Description: A synthetic analog of halichondrin B derived from the marine sponge Halichondria okadai. Shows an antitumor effect by arresting
the cell cycle through inhibition of the growth of microtubules. Approved in over 85 countries including Japan, the United States, China andcountries in Europe and in Asia for use in the treatment of breast cancer. Approved in over 80 countries including Japan, the United States
and countries in Europe and in Asia for use in the treatment of liposarcoma (soft tissue sarcoma in Japan).
Monotherapy (Additional Formulation)
Liposomal formulation

―

JP/EU

PI

In combination with anti-PD-1 antibody nivolumab, joint development with Ono Pharmaceutical (Additional Formulation)
Liposomal formulation

Study 120

JP

PI/II

Development Code: H3B-6545

In-house

Indications / Drug class: Anticancer agent / ERα inhibitor

Oral

Description: An orally administered selective estrogen receptor (ER) α covalent antagonist that inhibits ERα wild type / ERα mutant. Expected
to show an antitumor effect against ER positive / HER2 negative breast cancers.
Breast cancer

Study 101

US/EU

PI/II

―

US/EU

PI

Breast cancer (in combination with CDK4/6 inhibitor
palbociclib)
Development Code: E7090 Generic Name: tasurgratinib

In-house

Indications / Drug class: Anticancer agent / FGFR1, FGFR2, FGFR3 inhibitor

Oral

Description: An orally administered fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3) selective tyrosine kinase inhibitor. Phase II
clinical study for unresectable cholangiocarcinoma (one of biliary tract cancers) with FGFR2 gene fusion is ongoing. It has been granted theorphan drug designation with a prospective indication for unresectable biliary tract cancer with FGFR2 gene fusion by the Ministry of Health,Labour and Welfare (MHLW) in Japan.
Cholangiocarcinoma

Study 201

Breast cancer

―

JP/CH

PII

JP

PI

Development Code: MORAb-202 Generic Name: farletuzumab ecteribulin (FZEC)

In-house

Indications / Drug class: Anticancer agent / Folate receptor α targeted antibody drug conjugate

Injection

Description: An antibody drug conjugate (ADC) with approved anticancer drug eribulin. Expected to show an antitumor effect against folate
receptor α-positive tumors by concentrating eribulin on tumor; inclusive of endometrial, ovarian, lung and breast cancers. Joint developmentwith Bristol Myers Squibb.
Non-small cell lung cancer

Study 203

US/EU

PII

Ovarian cancer, peritoneal cancer, fallopian tube cancer

Study 205

JP/US/EU

PII

Solid tumors

Study 201

US/EU

PI/II

Solid tumors

―

JP

PI

JP: Japan, US: the United States, EU: Europe, CH: China, SK: South Korea, P: (Clinical trial) Phase◎：Development progress from April 2023 onwards
Reference Data [R&D Pipeline] 20

August 2, 2023 / Eisai Co., Ltd.

Development Code: E7386

Collaboration (PRISM BioLab)

Indications / Drug class: Anticancer agent / CBP/β-catenin interaction inhibitor

Oral

Description: A CREB-binding protein (CBP) /β-catenin inhibitor that blocks the protein-protein interaction between CBP and β-catenin, andregulates Wnt signaling-dependent gene expression. Expected inhibition of Wnt signaling-dependent tumor growth.
Solid tumors (in combination with pembrolizumab)

Study 201

JP/US/EU

PI/II

Solid tumors―

JP/US/EUPI

Solid tumors (in combination with lenvatinib)―

JP/US/EUPI

Collaboration(Harvard University)

Injection

JPPI

In-house

Injection

US/EU

PI

Development Code: E7130
Solid tumors―

Development Code: E7766
Solid tumors―(3) Global Health
Development Code: E1224

Generic Name: fosravuconazole

In-house

Indications / Drug class: Antifungal agent / ergosterol synthesis inhibitor

Oral

Description: An ongoing collaboration with the Drugs for Neglected Diseases initiative (DNDi) for a new treatment for eumycetoma, a fungal
form of mycetoma with a particularly high unmet medical need, and one of the world's most neglected diseases. Eisai is mainly responsible fornon-clinical studies and the provision of the investigational drug. The Phase IIb/III clinical study is being conducted in Sudan by DNDi and theMycetoma Research Center of the University of Khartoum, Sudan. Supported by the Global Health Innovative Technology Fund (GHIT Fund).
Development Code: SJ733

Co-development(University of Kentucky)

Indications / Drug class: Antimalarial agent / ATP4 inhibitor

Oral

Description: Expected to be suitable for treatment in malaria-endemic areas, with rapid efficacy and safety, and providing lasting protection
against reinfection. The treatment might potentially solve the problem of increased resistance faced by current antimalarial medicines. In theongoing collaboration with the University of Kentucky, Eisai is responsible for the provision of drug substance and formulation manufacturing.
The Phase II clinical study is being conducted in Peru by the University of Kentucky. Supported by the GHIT Fund.
Development Code: AWZ1066S

Co-development (Liverpool
School of Tropical Medicine)

Indications / Drug class: Antifilarial agent / antiwolbachia mechanism

Oral

Description: An ongoing collaboration with the Liverpool School of Tropical Medicine and the University of Liverpool to jointly identify new drugs
effective against lymphatic filariasis and onchocerciasis (river blindness), both major types of filariasis. Eisai is responsible for the provision of
drug substance and formulation manufacturing. The Phase I clinical study is being conducted in the United Kingdom (UK) by the Liverpool
School of Tropical Medicine. Supported by the GHIT Fund and Medical Research Council in the UK.

JP: Japan, US: the United States, EU: Europe, CH: China, SK: South Korea, P: (Clinical trial) Phase◎：Development progress from April 2023 onwards
Reference Data [R&D Pipeline] 21

August 2, 2023 / Eisai Co., Ltd.

(4) Gastrointestinal Disorders
Development Code: AJG555 Product Name: MOVICOL

In-license (Norgine)

Indications / Drug class: Chronic constipation treatment / polyethylene glycol preparation

Oral

Description: An orally available constipation treatment consisting of a polyethylene glycol preparation which facilitates bowel movement
by regulating osmolality in the intestines. Approved for chronic constipation treatment for children of 2 years and above and adult patients inJapan. Development conducted by EA Pharma.
◎

Chronic constipation in children under 2 years of age(Additional Dosage and Administration)

Study CT3

Development Code: AJM347
Inflammatory bowel disease(Development conducted by EA Pharma)―

Development Code: EA1080
Inflammatory bowel disease(Development conducted by EA Pharma)―

Development Code: EA3571
Nonalcoholic steatohepatitis(Development conducted by EA Pharma)

―

JP

PIII

In-house

Oral

EU

PI

In-house

Oral

EU

PI

In-house

Oral

JP

PI

(5) OtherDevelopment Code: FYU-981 Generic Name: dotinurad

In-license (FUJI YAKUHIN)

Indications / Drug class: Treatment for Hyperuricemia and Gout / selective URAT1 inhibitor

Oral

Description: Dotinurad selectively inhibits URAT1, one of the uric acid transporters, thus preventing reabsorption of uric acid by kidneys andpromoting uric acid excretion in urine. In addition, it has a small effect on other transporters affecting uric acid secretion, so it reduces serum
uric acid levels at lower doses. Therefore, dotinurad is expected to have a low risk of side effects and drug interaction. In Japan, FUJI YAKUHIN
obtained manufacturing and marketing approval for dotinurad in January 2020. Eisai entered into a license agreement concerning thedevelopment and distribution in China in February 2020, and in five ASEAN countries in August 2021 with FUJI YAKUHIN.
Gout

Study 301

CH

PIII

Development Code: E6742

In-house

Indications / Drug class: Treatment for Systemic lupus erythematosus / TLR 7/8 inhibitor

Oral

Description: Toll-Like Receptors (TLRs) are receptors of the innate immune system, and activated TLRs initiate an inflammatory reaction or anantiviral response. E6742 is the inhibitor of oral and selective TLR7/8 which is associated with the pathogenesis of systemic lupus
erythematosus. This project has been selected by the Japan Agency for Medical Research and Development (AMED) for its Cyclic Innovation
for Clinical Empowerment (CiCLE) grant program.
Systemic lupus erythematosus

Study 101

Development Code: E8001
Rejection reaction associated with organ transplantation

―

JP

PI/II

In-house

Injection

JPPI

JP: Japan, US: the United States, EU: Europe, CH: China, SK: South Korea, P: (Clinical trial) Phase◎：Development progress from April 2023 onwards
Reference Data [R&D Pipeline] 22

August 2, 2023 / Eisai Co., Ltd.