First-in-Class Plasma Biomarker Screening Method to Identify Participants for Phase III AHEAD 3-45 Study Announced

Tokyo2021December 6PR Newswire -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, hereinafter "Eisai") and Biogen Inc. (Nasdaq: BIIB, Headquarters: Cambridge, Massachusetts, CEO: Michel Vounatsos, hereinafter "Biogen") announced research findings exploring the use of plasma biomarkers in the Phase III AHEAD 3-45 study of Lecanemab (BAN2401), an investigational anti-amyloid beta (Aβ) protofibril antibody. AHEAD 3-45 is the first preclinical Alzheimer's disease (AD) trial using these biomarkers to detect AD pathology and potentially accelerate the screening process. The Alzheimer's Clinical Trials Consortium (ACTC) announced the findings at the 2021 Clinical Trials on Alzheimer's Disease (CTAD) conference held from November 9 to 12, 2021, in Boston, Massachusetts.

The AHEAD 3-45 clinical study will evaluate the efficacy of Lecanemab in preclinical AD and amyloid-elevated subjects, as well as in early preclinical AD and moderate amyloid subjects. In September 2021, Eisai began a rolling submission of the Biologics License Application (BLA) for Lecanemab to the U.S. Food and Drug Administration (FDA) through the accelerated approval pathway for the treatment of early AD.

Phase III AHEAD 3-45 Study Includes Two Sister Trials (A3 and A45), Investigating Specific Dosing Regimens Based on Baseline Brain Amyloid Levels Determined by PET Scans Showing Moderate Amyloid in A3 and Elevated Amyloid in A45. As the First-of-Its-Kind Approach in a Preclinical AD Trial, the Study Will Focus on Determining the Potential Role of Plasma Biomarkers in Identifying Cognitively Unimpaired Individuals Most Suitable for Positron Emission Tomography (PET) Imaging, the Current Standard Method for Determining Treatment Approaches.

Blood samples will be collected during a brief initial visit to determine the Aβ42/40 ratio, which previous studies have shown to be a potentially reliable predictor of brain amyloid levels and can be used to determine suitability for PET imaging. Based on the PET imaging results, subjects will be assigned to the A3 or A45 trial.

As of October 18, 2021, data from 659 participants were available for analysis. The adjusted Aβ42/40 ratio demonstrated excellent predictive ability for determining suitability for amyloid PET (AUC of 0.87), indicating that plasma screening has the potential to significantly reduce the number of PET scans required for full enrollment in A3 and A45.

Dr. Michael Irizarry, Vice President of Eisai and Deputy Chief Clinical Officer of the Neurology Business Group, stated: "The screening process for AD can be time-consuming and expensive. It is necessary to accelerate and improve the efficiency of identifying individuals who may be suitable for current and future AD treatments based on cognitive tests and confirmation of elevated amyloid levels in the brain. Eisai is pioneering new ground in treatment by incorporating plasma screening into clinical research for preclinical AD individuals. We are optimistic that this new approach will help identify patients with elevated brain amyloid levels and reduce the need for diagnostic amyloid PET scans or lumbar punctures."

This press release discusses the experimental use of the drug under development and does not intend to convey conclusions about its efficacy or safety. There is no guarantee that such an experimental drug will successfully complete clinical development or gain approval from health authorities.

[Editor's Note]

1.AboutLecanemab（BAN2401）

Lecanemab is an investigational humanized monoclonal antibody intended for the treatment of Alzheimer's disease (AD), and is the result of a collaborative development effort between Eisai and BioArctic. Lecanemab selectively binds to, neutralizes, and eliminates soluble, toxic β-amyloid (Aβ) protein aggregates (protofibrils), which are considered to accelerate the neurodegenerative process in AD. As such, Lecanemab may impact the disease's pathological mechanisms and slow disease progression. In terms of pre-specified analysis results at 18 months of treatment, Study 201 demonstrated reduced brain Aβ accumulation in early AD subjects (P<0.0001) and slowed disease progression as measured by ADCOMS* (P<0.05). The study did not meet its primary endpoint at 12 months of treatment**. Following the core phase and a treatment gap period (average 24 months), an open-label extension of Study 201 was initiated to evaluate safety and efficacy, which is currently ongoing.

According to the agreement signed with BioArctic in December 2007, Eisai obtained global rights for the research, development, manufacturing, and marketing of Lecanemab for the treatment of AD. In March 2014, Eisai and Biogen entered into a co-development and commercialization agreement for Lecanemab, which was revised by both parties in October 2017. Currently, based on the results of the Phase II clinical study (Study 201), a pivotal Phase III clinical study (Clarity-AD) of Lecanemab for symptomatic early AD is underway. In July 2020, a Phase III clinical study (AHEAD 3-45) was initiated for preclinical AD individuals (who are clinically normal but have moderate or elevated levels of amyloid in the brain). The AHEAD 3-45 study is being conducted through a public-private partnership model between the Alzheimer's Clinical Trials Consortium (funded by the National Institute on Aging, a division of the U.S. National Institutes of Health, providing infrastructure for academic clinical trials related to Alzheimer’s disease and related dementias in the U.S.) and Eisai and Biogen.

*ADCOMS (AD Composite Score) developed by Eisai combines items from the ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale), CDR (Clinical Dementia Rating), and MMSE (Mini-Mental State Examination) scales to sensitively detect clinical functional and memory changes associated with early AD symptoms.

**Compared with placebo, the estimated probability of slowing clinical decline by ≥25% from baseline at 12 months of treatment as measured by ADCOMS is ≥80%.

2.Eisai and Biogen's Collaboration in Alzheimer's Disease

Eisai and Biogen have collaborated on the development and commercialization of AD treatment drugs. Eisai is the lead developer of Lecanemab.

3.Eisai andBioArcticCollaboration in Alzheimer's Disease

Since 2005, BioArctic has established a long-term collaboration with Eisai for the development and commercialization of treatments for Alzheimer's disease (AD). In December 2007, a commercialization agreement for the antibody Lecanemab was signed, and in May 2015, a development and commercialization agreement for the backup AD antibody Lecanemab was signed. Eisai is responsible for the clinical development, regulatory submissions, and commercialization of the AD products. BioArctic does not bear the development costs for Lecanemab intended for AD treatment.

4.Regarding the Alzheimer's Disease Clinical Trials Consortium (ACTC) andAHEAD 3-45Test

Funded by the National Institute on Aging of the National Institutes of Health (Grant Number U24AG057437), the ACTC provides infrastructure for academic clinical trials related to Alzheimer's disease and associated dementias. The consortium, composed of the University of Southern California, Harvard University, and Mayo Clinic, includes expert units supporting clinical trial design, biostatistics, informatics, medical safety, regulatory oversight, recruitment, clinical operations, data management, study site monitoring, a biomarker laboratory and repository, and neuroimaging. The ACTC encompasses 35 leading clinical research centers across the United States.

AHEAD 3-45 is a Phase III clinical study conducted by ACTC, Eisai, and Biogen in a public-private partnership model.

5.About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global pharmaceutical company headquartered in Japan. The corporate philosophy of Eisai Co., Ltd. is based onConcern for Human Health (hhc）Philosophy: Always putting the interests of patients and their families first, contributing to the enhancement of their well-being. With a global network of research institutions, production bases, and marketing subsidiaries, the company is committed to providing innovative products targeting unmet medical needs, with a particular focus on strategic areas such as neurology and oncology.hhcConcept.

Eisai Plans to Leverage Experience Gained from the Development and Launch of Alzheimer's Disease Treatment Drugs to Establish the "Eisai Dementia Platform." Through this platform, Eisai aims to build a "Dementia Ecosystem" in collaboration with partners such as medical institutions, diagnostic development companies, research organizations, biotech venture firms, private insurance agencies, financial sector, fitness clubs, automobile manufacturers, retailers, and care facilities to bring new benefits to dementia patients and their families. For more information about Eisai Co., Ltd., please visithttps://www.eisai.com。

6.About Eisai USA

At Eisai America,Concern for Human Health (hhc）is our goal. We prioritize the interests of patients and their families, contributing to the enhancement of their well-being. As the U.S. subsidiary of Eisai Co., Ltd., headquartered in Tokyo, our dedication to patients drives us to strive for the discovery and development of innovative therapies to address unmet medical needs. Eisai is a fully integrated pharmaceutical company with operations in two global business areas: oncology and neurology (dementia-related diseases and neurodegenerative disorders). Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery laboratories are in Massachusetts and Pennsylvania; and our global demand chain organizations are in Maryland and North Carolina. For more information about Eisai, please visitwww.eisai.com/US, and follow ourTwitterAndLinkedInAccount.

7.About Biogen

As a pioneer in neuroscience, Biogen discovers, develops, and delivers innovative therapies for patients worldwide who are affected by serious neurological diseases. Founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp, Biogen was one of the world's first biotechnology companies. Today, Biogen has a leading portfolio of treatments for multiple sclerosis, introduced the first approved therapy for spinal muscular atrophy, and is providing the first and only treatment approved for the defining pathology of Alzheimer’s disease.

Biogen is also commercializing biosimilars and is committed to advancing the most diversified pipeline in the neuroscience field, which will change the standard of care for patients in several areas with highly unmet medical needs.

In 2020, Biogen launched a bold 20-year, $250 million initiative aimed at addressing the closely interconnected issues of climate, health, and equity. Healthy Climate, Healthy Lives™ aims to eliminate fossil fuels from the company’s operations and establish partnerships with renowned institutions to advance scientific progress, improve human health outcomes, and support underserved communities in healthcare.

The company frequently posts information on its website, www.biogen.com, that may be important to investors. For more information, please visitwww.biogen.com, and on social media -Twitter、LinkedIn、Facebook、YouTubeFollow Biogen's account.

8.Biogen Safe Harbor

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, regarding the potential clinical effects of Lecanemab; the potential benefits, safety, and efficacy of Lecanemab; potential regulatory discussions, submissions, and approvals and their timing; anticipated data readouts from the Clarity AD or AHEAD 3-45 studies; the treatment of Alzheimer's disease; the expected benefits and potential of the collaboration between Biogen and Eisai; the potential of Biogen’s commercial business and research and development programs, including Lecanemab; and statements regarding risks and uncertainties associated with drug development and commercialization. These forward-looking statements can be identified by words such as “aim,” “anticipate,” “believe,” “can,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “might,” “potential,” “will,” and other words of similar meaning. Drug development and commercialization involve high risks, and only a small number of research and development projects ultimately succeed in achieving product commercialization. Results from early-stage clinical trials may not represent the full results or all results of later-stage or larger-scale clinical trials, nor can they ensure that a drug will receive regulatory approval. You should not place undue reliance on these statements or the published scientific data.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including but not limited to: unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; the occurrence of adverse safety events; risks related to unexpected costs or delays; the risk of other unexpected obstacles; submissions to regulatory authorities potentially taking longer or being more difficult to complete than expected; regulatory authorities possibly requiring additional information or further studies, or failing to approve or delaying the approval of Biogen’s product candidates (including Lecanemab); the timing and content of submissions to regulatory authorities and the decision-making by regulatory authorities regarding Lecanemab; uncertainties surrounding the successful development and potential commercialization of Lecanemab; failure to protect and enforce Biogen's data, intellectual property, and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; third-party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on Biogen’s business, operating results, and financial condition. The above forward-looking statements list many, but not all, of the factors that could cause actual results to differ from Biogen’s expectations as set forth in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in Biogen’s most recent annual or quarterly report and other reports filed with the U.S. Securities and Exchange Commission. These forward-looking statements are based on Biogen’s current beliefs and expectations and speak only as of the date of this press release. Biogen has no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments, or otherwise.