11．Major R&D Pipeline
NCT: Identification number of Clinical Trials.gov, jRCT: Identification number of Japan Registry of Clinical Trials
JP: Japan, US: the United States, EU: Europe, CH: China, SK: South Korea, P: (Clinical trial) Phase
IIS: Investigator-initiated study ◎: Development progress from April 2024 onwards(1) Neurology
Development Code: BAN2401

Generic Name: lecanemab

Product Name: Leqembi

In-license (BioArctic AB)
Injection (intravenous infusion,subcutaneous 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. For the treatment of early AD, it
has been approved in Japan, the United States, China, South Korea, Hong Kong and Israel, and applications have been filed mainly in Europe,
Canada, Great Britain and Australia. In July 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines
Agency adopted a negative opinion on the agent’s Marketing Authorization Approval (MAA). Eisai is initiating process for seeking a
re-examination of the CHMP opinion. Development underway for maintenance dosing by intravenous infusion and subcutaneous injection.
Joint development with Biogen Inc.
Early AD
Study 301 (Clarity AD)

NCT03887455

Intravenous maintenance dosing for early AD(Additional Dosage and Administration)
Study 201/301

Development Code: E2007

Approval (April 2024)
Submission (accepted: January 2023)

US◎Submission (accepted: June 2024)

US◎

Rolling Submission(initiated: May 2024)

NCT03887455

Preclinical AD(Additional Indication)
Study 303 (AHEAD 3-45)◎

NCT01767311／NCT03887455

Maintenance dosing of a subcutaneous injection formulation for early AD(Additional Formulation)
Study 301

Asia (SK)EU

JP/US/EUPIII

NCT04468659
Generic Name: perampanel

Product Name: Fycompa

In-house

Indications / Drug class: Antiepileptic agent / AMPA receptor antagonist

Oral / Injection

Description: Selectively inhibits the AMPA receptor (a glutamate receptor subtype) activation by glutamate. Approved as an adjunctive therapy
for partial-onset seizures mainly in Japan, Europe, China and in Asia. Approved for monotherapy in Japan and China. Also approved as an
adjunctive therapy for primary generalized tonic-clonic seizures mainly in Japan, Europe, China and Asia. An oral suspension formulation has
been approved in Europe and China. Fine granule and injection formulations have been approved in Japan. In January 2023, the commercial
rights in the United States were transferred.
Adjunctive therapy for primary generalized tonic-clonic seizures(Additional Indication)
Study 332
Development Code: E2006

CH◎Approval (April 2024)

NCT01393743
Generic Name: lemborexant

Product Name: Dayvigo

Indications / Drug class: Insomnia treatment / Orexin receptor antagonist

In-house
Oral

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 mainly inJapan, the United States and Asia.
Insomnia disorderStudy 311

NCT04549168

CHReference Data [R&D Pipeline] 17

Submission(accepted: January 2024)

August 2, 2024 / Eisai Co., Ltd.

Development Code: E0302

Generic Name: mecobalamin

In-house

Indications / Drug class: Treatment for Amyotrophic lateral sclerosis (ALS)

Injection

Description: Ultrahigh-dose of mecobalamin that is 100 times the approved dose used for the treatment of peripheral neuropathy (as a singledose).
ALS
JETALS (IIS)
Development Code: E2023

JP

NCT03548311
Generic Name: lorcaserin

Submission(January 2024)

In-license (Arena Pharmaceuticals)

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 theUnited States, and the Phase III clinical study is underway for this indication. U.S. Food and Drug Administration has designated it as an orphan
drug for Dravet syndrome.
Dravet syndromeStudy 304

USNCT04572243

PIIICollaboration (University CollegeLondon)

Development Code: E2814
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 Eisaiand 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 (Phase II/III study
Tau NexGen).
Dominantly inherited AD
Tau NexGen studyNCT05269394

Dominantly inherited AD
Study 103

NCT04971733

JP/US/EU

PII/III

US/EUPIb/II

Development Code: E2511

In-house

Indications / Drug class: TrkA integrated synapse regenerant

Oral

AD

USPI

Development Code: E2025

In-house

Indications / Drug class: Anti-EphA4 antibody

Injection

ADUS

PI

Development Code: E2086

In-house

Indications / Drug class: Orexin receptor agonist

Oral

Narcolepsy

USPIb

Development Code: EA4017

In-house

Indications / Drug class: ―Oral

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

JP

Reference Data [R&D Pipeline] 18PI

August 2, 2024 / Eisai Co., Ltd.

(2) Oncology
Development Code: E7080

Generic Name: lenvatinib

Product Name: Lenvima

Indications / Drug class: Anticancer agent / kinase inhibitorIn-house
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 and hepatocellular carcinoma (first-line) mainly in Japan, the United States, Europe, China and Asia. Also approved for usein the treatment of thymic carcinoma in Japan. As a combination therapy with everolimus, approved for use in the treatment of renal cellcarcinoma (second-line) mainly in the United States, Europe and Asia. As a combination therapy with pembrolizumab, approved for use in thetreatment of renal cell carcinoma (first-line) mainly in Japan, the United States, Europe and Asia, and approved for use in the treatment ofendometrial carcinoma (following prior systemic therapy) mainly in Japan, the United States, Europe and Asia, including conditional approval.
The agent is marketed under the product name Kisplyx only for the renal cell carcinoma indication in Europe. Joint development with Merck &Co., Inc., Rahway, NJ, USA, through an affiliate.
In combination with anti-PD-1 therapy pembrolizumab, joint development with Merck & Co., Inc., Rahway, NJ, USA, through an affiliate(Additional Indication)
Hepatocellular carcinoma(in combination with transcatheter arterial chemoembolization) / First-line
LEAP-012

Esophageal carcinoma (in combination with chemotherapy) / First-line
LEAP-014

NCT04949256

Gastric cancer (in combination with chemotherapy) / First-line
LEAP-015

NCT04662710

Head and neck cancer / Second-line
LEAP-009

JP/US/EU/CH

PIII

JP/US/EU/CH

PIII

JP/US/EU/CH

PIII

US/EUPII

NCT04246177

NCT04428151

In combination with anti-PD-1 antibody nivolumab, joint development with Ono Pharmaceutical (Additional Indication)
Hepatocellular carcinoma
Development Code: E7389

JP
Generic Name: eribulin

Product Name: Halaven

Indications / Drug class: Anticancer agent / microtubule dynamics inhibitor

PIb
In-house
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 mainly in Japan, the United States, Europe, China and Asia for use in
the treatment of breast cancer. Approved including Japan, the United States, Europe, China and Asia for use in the treatment of liposarcoma(soft tissue sarcoma in Japan).
Monotherapy (Additional Formulation)
Liposomal formulation

JP/EUPI

In combination with anti-PD-1 antibody nivolumab, joint development with Ono Pharmaceutical (Additional Formulation)
Liposomal formulation
Study 120JP

NCT04078295

PIb/II

Development Code: E7090 Generic Name: tasurgratinib

In-house

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

OralDescription: An orally administered fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3) selective tyrosine kinase inhibitor. It has been
granted the orphan drug designation with a prospective indication for unresectable biliary tract cancer with FGFR2 gene fusion by the Ministryof Health, Labour and Welfare (MHLW) in Japan.
Biliary tract cancer with FGFR2 gene fusion
Study 201
Breast cancer

NCT04238715

JPSubmission (December 2023)

JPPIbReference Data [R&D Pipeline] 19

August 2, 2024 / Eisai Co., Ltd.

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

In-houseIndications / Drug class: Anticancer agent / Folate receptor α targeted antibody drug conjugate (ADC)

Injection

Description: ADC which combines anti-folate receptor α (FRα) antibody with approved anticancer drug eribulin via its linker. Expected to show
an antitumor effect against FRα-positive tumors by concentrating eribulin on tumor; inclusive of endometrial, ovarian, lung and breast cancers.
In June 2024, Eisai agreed to end its global strategic collaboration with Bristol Myers Squibb for co-development and co-commercialization,and moved to solo global development and commercialization.
Non-small cell lung cancer
Study 203

NCT05577715

Ovarian cancer, peritoneal cancer, fallopian tube cancer
Study 205

NCT05613088

Solid tumors
Study 201

NCT04300556

US/EUPII

JP/US/EUPIIUS/EUPI/II

Development Code: BB-1701

In-house

Indications / Drug class: Anticancer agent / HER2 targeted ADC

Injection

Description: ADC which combines anti-HER2 antibody with approved anticancer drug eribulin via its linker. Expected to show an antitumor
effect against HER2-positive tumors by concentrating eribulin on tumor; inclusive of breast cancer. Joint development agreement with Bliss
Biopharmaceutical (Hangzhou) Co., Ltd. with option rights for a strategic collaboration.
Breast cancer
Study 205

JP/US

NCT06188559

PIIDevelopment 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)

JP/US/EU

PIb/II

Solid tumors

JP/US/EUPI

Solid tumors (in combination with lenvatinib)

JP/US/EU

PIb

Study 201

NCT05091346

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 (in combination with CDK4/6 inhibitor palbociclib)

US/EU

PIb

Development Code: E7130

Collaboration (Harvard University)

Indications / Drug class: Anticancer agent

Injection

Solid tumors

JPPI

Development Code: E7766

In-house

Indications / Drug class: Anticancer agent

Injection

Solid tumors

US/EUReference Data [R&D Pipeline] 20

PIb

August 2, 2024 / Eisai Co., Ltd.

(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 fungalform 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. A Phase IIb/III clinical study was conducted in Sudan by DNDi and theMycetoma Research Center of the University of Khartoum, Sudan. Currently, preparation for regulatory filing to the regulatory authorities(National Medicines and Poisons Board) in Sudan is underway. 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

OralDescription: 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 ofTropical 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 ofdrug 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.

(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 CT3JPPIIIjRCT2031230142

Development Code: AJM347

In-house

Indications / Drug class: ―Oral

Inflammatory bowel disease(Joint development conducted by EA Pharma with Ensho Therapeutics, Inc)

EUPI

Development Code: EA1080

In-house

Indications / Drug class: ―Oral

Inflammatory bowel disease(Joint development conducted by EA Pharma with Ensho Therapeutics, Inc)

EUPI

Development Code: EA3571

In-house

Indications / Drug class: ―Oral

Metabolic dysfunction-associated steatohepatitis(Development conducted by EA Pharma)

JP
Reference Data [R&D Pipeline] 21PI
August 2, 2024 / Eisai Co., Ltd.

(5) Other
Development 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.
Asia(Philippines)

Gout, hyperuricemia
Gout
Study 301

CH

NCT05007392

Submission(September 2023)
Submission(accepted: January 2024)

Development Code: E6742

In-house

Indications / Drug class: Treatment for Systemic lupus erythematosus (SLE) / 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 SLE. 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.
SLEStudy 101

JP

NCT05278663

PI/IIDevelopment Code: E8001

In-house

Indications / Drug class: ―Injection

Rejection reaction associated with organ transplantation

JPReference Data [R&D Pipeline] 22PI

August 2, 2024 / Eisai Co., Ltd.