March 22, 2022
Sysmex Corporation
Eisai Co., Ltd.

Sysmex Presents Academic Report in Effort to Create a Simple Blood
Test to Diagnose Alzheimer’s Disease
The Content Presented at the International Conference on Alzheimer's & Parkinson's Diseases:(AD/PDTM 2022)

Sysmex Corporation (HQ: Kobe, Japan; Chairman and CEO: Hisashi Ietsugu; hereafter, “Sysmex”)
and Eisai Co., Ltd. (Headquarters: Tokyo; CEO: Haruo Naito; hereafter, “Eisai”) are aiming toleverage their individual technologies and expertise in the creation of next-generation diagnosticagents that may aid in early diagnosis of dementia, treatment selection, and regular confirmation oftreatment efficacy. Sysmex and Eisai have a non-exclusive comprehensive agreement for thecreation of novel diagnostic agents for the dementia area.
Sysmex and Eisai announced today that an oral presentation on the use of the HISCL™ AutomatedImmunoassay System in the clinical evaluation of the plasma Aβ1-42/Aβ1-40 ratio was delivered at theInternational Conference on Alzheimer’s & Parkinson’s Diseases (AD/PD™ 2022) held in Barcelona,
Spain from March 15 to 20 2022.
Presentation Fully Automated Plasma Beta-Amyloid Immunoassays Predict Amyloid Pathology
titleAuthors

Defined by Amyloid PET
Kazuto Yamashita1, Masao Miura1, Shunsuke Watanabe1, Kengo Ishiki1, Yuji
Arimatsu2, Yasuhiro Irino1, Toshiko Kubo3, Kei Hagino2, Kota Nagai4, David Verbel5,Akihiko Koyama6, Shobha Dhadda7, Hayato Niiro8, Shigeki Iwanaga1, Toshiyuki
Sato1, Tomokazu Yoshida9, Atsushi Iwata10
1CentralResearch Laboratories, Sysmex Corporation, Kobe, Japan; 2Business

Incubation Division, Sysmex Corporation, Kobe, Japan; 3Sysmex R&D Center
Americas, Mundelein, Illinois, USA;
Department, Eisai Co., Ltd., Japan;

4Japanand Asia Clinical Development

5Biostatistics, Eisai Inc., Woodcliff Lake, NJ,

USA; 6Translational Science, Eisai Inc., Woodcliff Lake, NJ, USA; 7Biostatistics andProject Operations, Eisai Inc., Woodcliff Lake, NJ, USA; 8Medical Affairs Division,
SysmexCorporation,Kobe,

Japan;

9Sysmex

Corporation,

Kobe,

Japan;

10Department of Neurology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

Type ofpresentation

Virtual, On-Demand Oral

Overview of Accumulation of β-amyloid peptide (Aβ) (amyloid pathology) in the brain is a hallmark
presentation of Alzheimer’s disease (AD). Several clinical trials on disease-modifying therapies(DMTs) targeting Aβ have been conducted. The US Food and Drug Administration
has recently granted accelerated approval for an anti-amyloid antibody for early AD.
Given this background, there is an increasing need for simple, cost-effective
diagnostic methods of detecting amyloid pathology in the brain.
Our group previously reported that amyloid PET status was correlated with Aβ1-42/
Aβ1-40 ratio in plasma (hereafter, “plasma Aβ ratio”) and that amyloid pathology in thebrain could potentially be predicted using blood biomarkers.*1 Our research has
focused on the plasma Aβ ratio using clinical specimens. In this presentation, we
conducted a clinical evaluation of the plasma Aβ ratio measured using the HISCL
Automated Immunoassay System (Sysmex) in comparison with amyloid PET statusdetermined by the Centiloid method*2 in 180 patients (Discovery Study) and 191
patients (Validation Study) clinically diagnosed with mild AD or mild cognitive
impairment.
(Results)✓In the Discovery Study, the plasma Aβ ratio was significantly lower in theAmyloid PET positive group as compared to the negative group and it
predicted amyloid PET status with high accuracy: sensitivity 97.5%, specificity
80.8%, AUC = 0.93 (0.90 – 0.97).

✓In the Discovery Study, the plasma Aβ ratio and Centiloid unit (CL) weresignificantly correlated with a Spearman rank correlation coefficient*3 of -0.75(P<0.001), and this indicates that our assay could be indicative of the amountof Aβ accumulation in the brain. Also, we observed inconsistency in several
patients, who had a positive plasma Aβ ratio and a negative CL. This
inconsistency has also been found in other studies and it was reported that it
represented an increased risk of conversion to PET positive as compared toAβ ratio negative subjects.*4 Our results suggest that the plasma Aβ ratio
measured using the HISCL Automated Immunoassay System could
potentially indicate presence of amyloid pathology in the brain at an earlier
stage when it was not detectable by PET.

Since measurement of plasma Aβ1-42 and Aβ1-40 in the HISCL is fully automatedimmunoassay that is less invasive and more accessible, it may contribute to thediagnosis of AD in routine clinical practice. We believe that the plasma Aβ cancontribute to early diagnosis, of AD, treatment selection and monitoring of treatment
effect.

[Notes]*1 The 18th R&D Meeting (2021, Sysmex)*2 Klunk WE et al, Alzheimer’s Dementia (2014)*3 Shows significant correlation between data from 2 quantitative data distributions. In the presentanalysis, we calculated Spearman’s rank correlation coefficients, which indicate correlations
between rank data.
*4 Schindler SE et al, Neurology, 93, e1647-e1659 (2019)