October 16, 2023
Eisai Co., Ltd.

No.23-65

EISAI TO PRESENT NEW DATA FROM LEQEMBI® (LECANEMAB-IRMB) PHASE 3 CLARITY AD
STUDY AND OTHER ALZHEIMER’S DISEASE PIPELINE RESEARCH AT THE CLINICAL TRIALS ON
ALZHEIMER'S DISEASE (CTAD) CONFERENCE
Update on LEQEMBI Investigational Subcutaneous Formulation
Eisai Co. Ltd (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that the company will
present new data from the phase 3 Clarity AD study for its Alzheimer’s disease (AD) treatment LEQEMBI®
(lecanemab-irmb) 100 mg/mL injection for intravenous use and new data on the subcutaneous formulationin development at the 16th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference. The conference
will be held in Boston, Massachusetts, United States and virtually from October 24 to 27, 2023. In addition to
the data presented on Eisai’s anti-amyloid beta (Aβ) protofibril* antibody LEQEMBI, phase 1 data for E2511,
an investigational tropomyosin receptor Kinase A (TrkA) positive allosteric modulator (PAM), will be presented
as well as other research from the company’s AD pipeline. At the conference, Eisai will present data andresearch in five oral and ten poster presentations. BioArctic will give an oral presentation on lecanemab.
Late-Breaking Symposium 4 – Lecanemab for early Alzheimer’s Disease: Long-Term Outcomes,
Predictive Biomarkers, and Novel Subcutaneous Administration•In a late-breaking symposium on October 25 from 17:25-18:05 EDT, Eisai will present the latest
data from the Clarity AD optional tau PET longitudinal substudy. The presentation will include
a post-hoc analysis of the low and intermediate + high-tau subgroups, with the low-tau
subgroup representing early stages of disease studied specifically in the phase 3 core study,
and the open-label extension study. An update on the investigational subcutaneous
formulation, including interim safety and effect on amyloid in the brain measured by amyloid
PET, will be provided.

•Distinguished faculty members Christopher van Dyck M.D., Keith Johnson M.D. and Reisa Sperling
M.D. will discuss the findings in a panel led by Michael Irizarry, M.D., MPH, Eisai.

•A live webcast of this symposium can be viewed on the Eisai Co., Ltd. website.

“Alzheimer’s disease is a progressive and relentless condition that requires early diagnosis1,2,3 and continuedtreatment. LEQEMBI supports neuronal function in Alzheimer’s disease 1,4,5 by clearing highly toxic
protofibrils3,4 that can continue to cause neuronal injury and death well after plaques are cleared,”5,6,7,8 said
Michael Irizarry, MD, MPH, Senior Vice President, Clinical Research, Neurology, Deputy Chief Clinical Officer,Clinical Evidence Generation, Eisai. “We look forward to sharing the new LEQEMBI low-tau subgroup dataand subcutaneous data at CTAD 2023.”
Other major oral presentations include:•Lecanemab: Binding profiles of lecanemab and donanemab to different amyloid-beta species (OC19,presentation by BioArctic).

•E2511, a novel TrkA modulator, engages its CNS cholinergic target in a phase 1 clinical study (OC34).

•

Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer’s disease (OC2).

The full list of presentations about Eisai assets and research follows.
■ Late Breaking Symposium 4
The Symposium title: Lecanemab for Early Alzheimer’s Disease: Long-Term Outcomes, Predictive
Biomarkers and Novel Subcutaneous Administration from 17:25 to 18:05 EDT on October 25, 2023.
Presentation Title
Clarity AD: Review of the Mechanism-Based Rationale and Results of the Lecanemab Phase 3
Trial
Biomarker Assessments from Clarity AD: A Focus on Downstream Implications of Targeting
Protofibrils* and Tau as a Predictive Biomarker
Lecanemab for the Treatment of Early Alzheimer’s Disease: The Extension of Efficacy Resultsfrom Clarity AD
Preliminary Update on Lecanemab Safety in Clarity AD Open-Label Extension, Including
Subcutaneous Formulation
Panel discussion, Q&A■ Oral Presentations
Asset/Project,

Presentation Number, Title

Presentation Time (EDT)
Lecanemab

OC19
Binding Profiles of Lecanemab and Donanemab to Different Amyloid-

October 26 (Thu) 14:50-15:05

beta Species(presentation by BioArctic)

Lecanemab
October 26 (Thu) 17:05-17:45(Late breaking symposium 6)
E2511
October 27 (Fri) 14:45-14:55

Presentation 3 in Late breaking symposium 6
Aβ42/Aβ40 and Phospho-tau217 Concentration Ratios Increase theAccuracy of Amyloid PET Classification in Preclinical Alzheimer'sDisease
OC34
E2511, a Novel TrkA Modulator, Engages its CNS Cholinergic Target ina Phase 1 Clinical StudyLB7Biomarker
October 25 (Wed) 8:45-9:00

PrecivityAD2™ Blood Test: An Analytically and Clinically Validated Test
Combining p-Tau217/np-Tau217 and Aβ42/40 Ratios to Identify BrainAmyloid(presentation by C2N)

Biomarker

OC2October 25 (Wed) 11:35-

Novel CSF Tau Biomarkers Can Be Used for Disease Staging of11:50

Sporadic Alzheimer's Disease

AD general
October 27 (Fri) 11:45-12:00

OC29
AI-based Enrichment Tools to Increase Efficiency of Alzheimer’sDisease Clinical Trials

■ Poster Presentations
Asset/Project

Presentation Number, Title
P018

Lecanemab

Recruitment Source, Eligibility and Reason for Prescreen-Fail AcrossSex, Race and Ethnicity: Preliminary Analysis of Prescreening Data fromthe AHEAD Study
P045

Lecanemab

ARIA by Clinical Subgroup and Baseline Amyloid PET Centiloid Levels
from the Lecanemab Clarity AD
LP011

Lecanemab

E2511

Biomarker

Impact of a Site Supplemental Funding Program to Alleviate Recruitment
Burden: Experiences in the Preclinical Alzheimer’s Disease AHEAD
Study
P044
Safety and Pharmacokinetics of Multiple Ascending Doses of E2511, aNovel TrkA Allosteric Modulator, in Healthy Volunteers
P070
Systematic Literature Review of the Clinical and Non-clinical Value ofImaging and Fluid Biomarker Testing to Diagnose, Identify and Monitor
Patients with Alzheimer’s Disease
P032

AD general

Planning the Next Generation of Alzheimer’s Disease Clinical Trials
Using Diverse Patient-level Database from the Critical Path for
Alzheimer’s Disease (CPAD) Consortium
P033

AD general

Critical Path for Alzheimer’s Disease (CPAD) Consortium: Data-Driven
Solutions for Clinical Trial Design and Informed Decision Making
LP003

AD general

Implications of Missing Data and Dropouts in Randomized Clinical Trials
in Early Alzheimer’s Disease

AD general

P145
Age-Specific Relative Comorbidity Burden of MCI: a US Database Study
P179

AD general

Development of a Mild Cognitive Impairment Risk Prediction Model
Using Electronic Health Record Data

This release discusses investigational uses of agents in development and is not intended to convey
conclusions about efficacy or safety. There is no guarantee that such investigational agents will successfullycomplete clinical development or gain health authority approval.
*Protofibrils•

One of the AD pathological features is the accumulation of clusters (plaques) of amyloid beta (Aβ) in thebrain. The formation of these plaques is the result of a continuous process by which individual Aβ proteinsjoin together, latching onto each other, one at a time, like adding links to a chain. 9 In the early part of thisprocess these small chains of Aβ are soluble and are toxic to the nerves within the brain.10,11

•The most toxic of the soluble chains is called a protofibril.3 Protofibrils are believed to contribute to thebrain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary rolein the cognitive decline associated with this progressive, debilitating condition. 1,2•Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via
multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing
direct damage to brain cell membranes and the connections that transmit signals between nerve cells or
nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD
by reducing damage to neurons in the brain and cognitive dysfunction. 12

MEDIA CONTACTS:
Eisai Co., Ltd.
Public Relations Department
TEL: +81 (0)3-3817-5120
Eisai Inc. (U.S.)
Libby Holman+ 1-201-753-1945
Libby_Holman@Eisai.com
Eisai Europe, Ltd.
(UK, Europe, Australia, New Zealand and Russia)
EMEA Communications Department+44 (0) 786 601 1272
EMEA-comms@eisai.net[Notes to editors]
1. About Lecanemab (generic name, U.S. brand name: LEQEMBI®),
Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab is ahumanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble(protofibril) and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted traditional approvalby the U.S. Food and Drug Administration (FDA) on July 6, 2023. LEQEMBI is an amyloid beta-directed
antibody indicated as a disease-modifying treatment for Alzheimer’s disease (AD) in the U.S. Treatment with
LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage ofdisease, the population in which treatment was initiated in clinical trials. There are no safety or effectivenessdata on initiating treatment at earlier or later stages of the disease than were studied. In Japan, Eisai received
approval from the Ministry of Health, Labour and Welfare (MHLW) on September 25, 2023 to manufacture
and market lecaenmab as a treatment for slowing progression of MCI and mild dementia due to AD.
Please see full Prescribing Information, including Boxed WARNING in the United States.
Eisai has also submitted applications for approval of lecanemab in EU, China, Canada, Great Britain,
Australia, Switzerland, South Korea and Israel. In China and Israel, the applications have been designatedfor priority review, and in Great Britain, lecanemab has been designated for the Innovative Licensing andAccess Pathway (ILAP), which aims to reduce the time to market for innovative medicines.
Eisai has completed a lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently
being evaluated in the Clarity AD (Study 301) open-label extension (OLE). A maintenance dosing regimen

has been evaluated as part of Study 201.
Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they
are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD
3-45 is conducted as a public-private partnership between the Alzheimer's Clinical Trial Consortium thatprovides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by theNational Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.
Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by
Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School ofMedicine in St. Louis, is ongoing and includes lecanemab as the backbone anti-amyloid therapy.
2. About E2511
E2511 is Eisai’ s in-house discovered and developed investigational novel molecule that directly binds totropomyosin receptor kinase A (TrkA); a nerve growth factor (NGF) located on the neural cell membrane.
E2511 could potentially promote recovery and synaptic remodeling of damaged cholinergic neurons. A Phase
1 study for E2511 is underway.
3. About the Collaboration between Eisai and Biogen for Alzheimer’s Disease
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments
since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally withboth Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decisionmaking authority. In Japan, Eisai and Biogen Japan will co-promote lecanemab, with Eisai distributing theproduct as the Marketing Authorization Holder.
4. About the Collaboration between Eisai and BioArctic for Alzheimer’s Disease
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development andcommercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture andmarket LEQEMBI for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The
development and commercialization agreement on the antibody LEQEMBI back-up was signed in May 2015.

References
1. LEQEMBI US Prescribing Information under Traditional Approval
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3. Hampel, H., Hardy, J., Blennow, K. et al. The Amyloid-β Pathway in Alzheimer’s Disease. Mol Psychiatry.
2021;26:5481–5503. https://doi.org/10.1038/s41380-021-01249-0
4. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med.
2023;388(1):9-21.
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dystrophy in PDAPP transgenic mice J Clin Invest. 2005;115(2):428-433. https://doi.org/10.1172/JCI23269.
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neurotoxicity in cortical neurons. J Neurosci. 1999;19(20):8876-84. doi: 10.1523/JNEUROSCI.19-2008876.1999. PMID: 10516307; PMCID: PMC6782787.
9. Alzheimer’s Association. (2022). Brain Tour Part 2 - Alzheimer’s Effect. Retrieved September 27, 2023,
from https://www.alz.org/alzheimers-dementia/what-is-alzheimers/brain_tour_part_2
10. Chen, Gf., Xu, Th., Yan, Y. et al. Amyloid beta: structure, biology and structure-based therapeutic
development. Acta Pharmacol. 2017;38:1205. https://doi.org/10.1038/aps.2017.28
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toxic soluble Aβ oligomers. Biophysics and Computational Biology. 2022;10.1073.
https://www.pnas.org/doi/epdf/10.1073/pnas.2210766119
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