Eisai To Present New Lecanemab Data Exploring Distinct Mechanism of Action and Clinical Outcomes, Disease State Symposium, and Other Pipeline Assets at the AD/PD™ 2022 Annual Meeting

TOKYO, March 10, 2022 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") announced today the company will present research from its robust Alzheimer's disease (AD) pipeline, including the latest findings on lecanemab, Eisai's investigational anti-amyloid beta (Aβ) protofibril antibody for the treatment of early AD, at the AD/PD™ 2022 International Conference on Alzheimer's and Parkinson's Diseases (AD/PD) from March 15-20 in Barcelona, Spain and virtually. The lecanemab data and additional research findings from Eisai's clinical development programs will be featured in 14 presentations. Lecanemab was granted Breakthrough Therapy and Fast Track designations by the U.S. Food and Drug Administration (FDA) in June and December 2021, respectively. Eisai anticipates completing lecanemab's rolling submission of a Biologics License Application for the treatment of early AD to the FDA under the accelerated approval pathway. We expect to complete this rolling submission in the first quarter of Eisai's fiscal year 2022, which begins April 1, 2022. Additionally, the readout of the Phase 3 confirmatory Clarity AD clinical trial will occur in the Fall of 2022. Eisai initiated a submission to the Pharmaceuticals and Medical Devices Agency (PMDA) of application data of lecanemab under the prior assessment consultation system in Japan in March 2022.

"Four key presentations at AD/PD 2022 advance our understanding of the mechanism of action of Eisai's investigational anti-amyloid beta protofibril antibody lecanemab and the therapy's clinical and safety profile, including amyloid-related imaging abnormalities, or ARIA, from the Phase 2b study and open-label extension, in the potential treatment of early Alzheimer's disease," said Michael Irizarry, M.D., Senior Vice President, Deputy Chief Clinical Officer, Neurology Business Group, Eisai Inc. "In addition to lecanemab, Eisai's robust pipeline includes compounds targeting the tau pathway, other pathways leading to neurodegeneration, and the testing of combination therapies that may be the optimal approach to treat or even prevent Alzheimer's disease."

The focus on AD has historically been on alleviating cognitive, functional, and behavioral symptoms, but there has been significant progress in understanding the biological mechanisms of the disease. Eisai's investigational pipeline aims to treat the range of underlying pathophysiology, including amyloid, tau and neurodegeneration.

"Because of the robust design of the lecanemab Phase 2b study, Eisai was able to design the Phase 3 confirmatory Clarity AD clinical trial to optimally verify lecanemab's clinical efficacy and safety in early Alzheimer's disease," said Ivan Cheung, Chairman, Eisai Inc., President Neurology Business Group and Global Alzheimer's Disease Officer, Eisai Co., Ltd. "Part of the recruitment strategy for the Clarity AD confirmatory trial was to ensure greater inclusion of ethnic and racial populations. While there is still important work to be done in ensuring minority populations' participation in clinical trials, Eisai is proud that approximately 25% of the total U.S. enrollment in Clarity AD consists of African American and Hispanic persons living with early Alzheimer's disease, which mirrors the U.S. Medicare population."

This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such investigational agent will successfully complete clinical development or gain health authority approval.

Major Presentations Provide Deeper Scientific Insights into Lecanemab's Mechanism of Action and Potential as a Treatment for Early AD

Onsite Symposium - Aβ Targeting Therapies in AD 2

• Science of the Amyloid Cascade and Distinct Mechanism of Action of Lecanemab – Data will be presented to show different anti-Aβ antibodies and their affinities to different Aβ species. AD is characterized by the presence of Aβ plaques and neurofibrillary tangles composed of tau protein. Genetic and biomarker studies point to Aβ aggregation as occurring early in the disease. There is a spectrum of aggregated Aβ species, ranging from soluble dimers, oligomers, protofibrils and insoluble fibrillar Aβ, which exist in a complex equilibrium in the AD brain. Soluble aggregated species such as protofibrils are considered to be toxic to neurons and are implicated in the neurodegenerative process in AD. Immunotherapy against Aβ has emerged as a promising treatment for AD. The mouse precursor antibody (mAb158) to lecanemab, was generated based on protofibrils formed by the Arctic mutation, which causes AD due to an enhanced propensity to form protofibrils.
• Key Trial Design Aspects and Clinical Outcomes of the Lecanemab Phase 2b (Study 201) Trial and Open-Label Extension (OLE) in Early Alzheimer's Disease – This presentation shares the latest results from the lecanemab Study 201 Core and OLE exploring the reduction of brain amyloid and the incidence and severity of amyloid-related imaging abnormalities (ARIA). Study 201 was a dose-ranging study that employed a Bayesian adaptive design with response adaptive randomization. The study demonstrated that lecanemab cleared amyloid plaques in a dose- and time-dependent manner and identified the 10 mg/kg IV biweekly dose as the dose most likely to slow cognitive decline in early AD, a hypothesis that will be verified in the Clarity AD Phase 3 study. In Study 201, lecanemab showed an overall rate of less than 10% incidence of ARIA-E at 10 mg/kg biweekly in the Core and OLE (<15% in ApoE4 carriers). The incidence of symptomatic ARIA-E was <2% in Core and OLE. This safety profile enables lecanemab to be initiated at the therapeutic dose without titration.
• Phase 2b (Study 201) Lecanemab Early Alzheimer's Disease Study Biomarker Results and Correlations with Clinical Outcomes – Discussion around the key biomarker findings and their correlation with clinical outcomes from the lecanemab Phase 2b Core and OLE studies. As part of this presentation, Dr. E. McDade from Washington University in St. Louis will provide an update on the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Tau NexGen trial, which is evaluating lecanemab combined with Eisai's investigational anti-microtubule binding region (MTBR) tau antibody E2814. Researchers will share:
• Evaluation of the association of amyloid plaque reduction and effects on clinical outcomes by lecanemab with peripheral measures of AD biomarkers in the randomized Core-phase 201.
• Results and modeling of changes in amyloid plaque and peripheral measures of AD biomarkers after lecanemab cessation in the Gap phase, and implications for lecanemab maintenance therapy.
• Update on Lecanemab Clinical Development, Including New Subcutaneous (SC) Formulation – Eisai will provide the latest information from the Phase 2b OLE study of lecanemab in early AD dosing substudy, Phase 3 study of lecanemab in early AD (Clarity AD), and Phase 3 study of lecanemab in preclinical AD (AHEAD 3-45). The rationale and clinical development strategy for SC lecanemab will be presented.

Other Key Presentations

• An invited presentation exploring the Aβ pathway Across Time and Space in AD will be led by Harald Hampel, MD, PhD, MSc, Chief Medical Officer, Senior Vice President, Head of Global Medical Affairs, Neurology Business Group at Eisai Inc.
• Baseline Tau PET in Clarity AD: A Phase 3 Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study Evaluating Lecanemab in Early Alzheimer's Disease
• Quantitative Systems Pharmacology (QSP) Amyloid Platform: Multiscale Computational Modeling of Aβ Biology and Its Interaction with Lecanemab Pharmacology
• Fully Automated Plasma β-Amyloid Immunoassays Predict Amyloid Pathology Defined by Amyloid PET

Eisai Disease State Virtual Symposium
Eisai will hold a virtual symposium titled, "Amyloid β Pathway: Evolving Scientific Knowledge and Clinical Implications for Alzheimer's disease," where esteemed faculty will review the effects of Aβ across cellular and systemic context, as well as across AD stages and therapeutic approaches. Featured speakers include Dennis J. Selkoe, MD, Bart De Strooper, MD, PhD, Susan Landau, PhD, Randall Bateman, MD.

The symposium will be held virtually Saturday, March 19, 2022, 11:40 a.m. - 1:25 p.m. Central European Time (GMT+1) and will be available online for three months following AD/PD 2022.

Complete List of AD/PD 2022 Presentations Relating to Eisai's Key Compounds and Research

Below please find a list of important presentations and symposia at this year's meeting. All presentations will be available online to registered participants via the AD/PD virtual platform.

Eisai Disease State Symposium

Biogen Abstract Presentations for Alzheimer's Disease

Eisai leads all actions on lecanemab, including clinical development, FDA interaction, and commercialization as part of the collaboration agreement with Biogen.

[Notes to editors]

1.     About Lecanemab (BAN2401)
Lecanemab is an investigational humanized monoclonal antibody for Alzheimer's disease (AD) that is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab selectively binds to neutralize and eliminate soluble, toxic amyloid-beta (Aβ) aggregates (protofibrils) that are thought to contribute to the neurodegenerative process in AD. As such, lecanemab may have the potential to have an effect on disease pathology and to slow down the progression of the disease. With regard to the results from pre-specified analysis at 18 months of treatment, Study 201 demonstrated reduction of brain Aβ accumulation (P<0.0001) and slowing of disease progression measured by ADCOMS* (P<0.05) in early AD subjects. The study did not achieve its primary outcome measure** at 12 months of treatment. The Study 201 open-label extension was initiated after completion of the Core period and a Gap period off treatment (average of 24 months) to evaluate safety and efficacy, and is underway.

2. About ADUHELM^® (aducanumab-avwa) 100 mg/mL injection for intravenous use
ADUHELM is indicated for the treatment of Alzheimer's disease. Treatment with ADUHELM should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with ADUHELM. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

ADUHELM is a monoclonal antibody directed against amyloid beta. The accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer's disease. The accelerated approval of ADUHELM has been granted based on data from clinical trials showing the effect of ADUHELM on reducing amyloid beta plaques, a surrogate biomarker that is reasonably likely to predict clinical benefit, in this case a reduction in clinical decline.

ADUHELM can cause serious side effects including: Amyloid Related Imaging Abnormalities or "ARIA". ARIA is a common side effect that does not usually cause any symptoms but can be serious. Although most people do not have symptoms, some people may have symptoms such as: headache, confusion, dizziness, vision changes and nausea. The patient's healthcare provider will do magnetic resonance imaging (MRI) scans before and during treatment with ADUHELM to check for ARIA. ADUHELM can also cause serious allergic reactions. The most common side effects of ADUHELM include: swelling in areas of the brain, with or without small spots of bleeding in the brain or on the surface of the brain (ARIA); headache; and fall. Patients should call their healthcare provider for medical advice about side effects.

As of October 2017, Biogen and Eisai Co., Ltd. are collaborating on the global co-development and co-promotion of aducanumab.

Please click here for full Prescribing Information, including Medication Guide, for ADUHELM.

3.     About the Joint Development between Eisai and Biogen for Alzheimer's Disease
Eisai and Biogen are collaborating on the joint development and commercialization of AD treatments. Eisai serves as the lead in the co-development of lecanemab.

4.   About the Collaboration between Eisai and BioArctic for Alzheimer's Disease
Since 2005, BioArctic has had a long-term collaboration with Eisai regarding the development and commercialization of drugs for the treatment of AD. The commercialization agreement on the lecanemab antibody was signed in December 2007, and the development and commercialization agreement on the antibody lecanemab back-up for AD, which was signed in May 2015. Eisai is responsible for the clinical development, application for market approval and commercialization of the products for AD. BioArctic has no development costs for lecanemab in AD.

5.   About the Collaboration between Eisai and Sysmex
Eisai and Sysmex have entered into a comprehensive non-exclusive collaboration agreement aimed at the creation of new diagnostics in the field of dementia in February 2016. Leveraging each other's technologies and knowledge, the two companies aim to discover next-generation diagnostics that will enable early diagnosis, selection of treatment options and regular monitoring of the effects of treatment for dementia.

6.   About E2814
An investigational anti-microtubule binding region (MTBR) tau antibody, E2814 is being developed as a disease-modifying agent for tauopathies including sporadic AD. Phase I clinical studies are underway. E2814 was discovered as part of the research collaboration between Eisai and University College London. E2814 is designed to prevent the spreading of tau seeds within the brains of affected individuals.

7.   About E2511
E2511 is Eisai's in-house discovered and developed investigational novel molecule that directly binds to tropomyosin 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.

8.   About Eisai Co., Ltd.
Eisai Co., Ltd. is a leading global pharmaceutical company headquartered in Japan. Eisai's corporate philosophy is based on the human health care (hhc) concept, which is to give first thought to patients and their families, and to increase the benefits that health care provides to them. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.

Leveraging the experience gained from the development and marketing of a treatment for Alzheimer's disease, Eisai aims to establish the "Eisai Dementia Platform." Through this platform, Eisai plans to deliver novel benefits to those living with dementia and their families through constructing a "Dementia Ecosystem," by collaborating with partners such as medical organizations, diagnostic development companies, research organizations, and bio-ventures in addition to private insurance agencies, finance industries, fitness clubs, automobile makers, retailers, and care facilities. For more information about Eisai Co., Ltd., please visit https://www.eisai.com.

9.   About Eisai Inc.
At Eisai Inc., human health care (hhc) is our mission and is the shared purpose that connects us to those we serve creating a network of powerful relationships that enables us to identify, understand and work to address the needs of people throughout their lives. We boldly push past the boundaries of science and aim to deliver life-changing therapies and health-related solutions that matter to people and society. We bring together science, technology and real-world expertise to pursue a world free from cancer, Alzheimer's disease and other neurodegenerative diseases.

Everything we do is guided by the simple principle that patients and their families come first, and we have a responsibility to listen to and learn from them.

Eisai Inc. is the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd. The company's presence in the U.S. includes three discovery centers as well as commercial, clinical development and global demand organizations. To learn more about Eisai, please visit us at www.eisai.com/US and follow us on Twitter and LinkedIn. For more information on our work in neurology, please visit the Eisai U.S. Neurology LinkedIn page.

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