Press release
August 29, 2018
KinoPharma, Inc.
National Institutes for Quantum and Radiological Science and Technology

KinoPharma and National Institutes for Quantum and Radiological Science andTechnology Launch Collaborative Research Project for Exploring New Drug
Development for Alzheimer’s Disease
KinoPharma, Inc., and the National Institutes for Quantum and Radiological Science and Technology are pleased
to announce that they have entered a contract for collaborative research on efficacy evaluation of the compound
KPO1143, developed by KinoPharma to prevent the accumulation of protein called tau (hereafter “tau protein”),1)
which is considered a cause of Alzheimer’s disease (AD). The National Institutes’ research group is led by MD &PhD Makoto Higuchi from the Department of Functional Brain Imaging Research of the National Institute ofRadiological Sciences (NIRS).

■ Background and objectives of R&D on AD
Under the public R&D funding of A­STEP by the Japan Science and Technology Agency (JST), KinoPharma, Inc.,embarked on research for discovering drugs that can inhibit excessive phosphorylation of tau protein, which may
trigger the abnormal aggregation of such protein, and eventually succeeded in acquiring a candidate compound,dubbed KPO1143.
This collaborative research is intended to evaluate the pharmacological actions of KPO1143 as a candidate
therapeutic drug for AD by administering the compound to mice with transgenically overexpressed human tau protein,
and verifying its inhibitory effects on tau protein accumulation in the living brain, using the PET2) tracer technology
developed by QST­NIRS.
In the project “Establishment of a research and development consortium on novel imaging diagnostics andtherapeutics targeting tau pathologies,” offered by the Japan Agency for Medical R&D (AMED), QST­NIRS
developed a PET tracer that allows the visualization of tau protein within the living brain. This collaborative researchaims to capitalize on the drug discovery platform including the efficacy evaluation system using tau protein as abiomarker.

■ About AD
According to the estimate of Alzheimer’s Disease International, one individual/person newly developed dementia
every 3 seconds worldwide as of 2015. In Japan, a survey conducted by a research group of the Ministry of Health,Labour and Welfare found that approximately 4.62 million patients had dementia as of 2012, and predicted that thenumber of patients will continue to increase. In the brain of patients with AD, who account for about half of alldementia patients, the accumulation of amyloid β (Aβ)3) and tau protein promotes the death of neurons, causing
symptoms such as forgetfulness. The pathological cause of AD has not been elucidated; thus, no curative treatment
has been established yet. In recent years, the accumulation of abnormal aggregation of tau protein has been widely
accepted as a cause of AD. Evidence showing that abnormal tau protein accumulating in the brain of AD patients arehighly phosphorylated may suggest a close relationship between tau protein phosphorylation and its
aggregation/accumulation.

■ About KinoPharma, Inc.
KinoPharma, Inc., is an academic biotech spin­off established in April 2005 by an entrepreneurial scientist, Professor
Masatoshi Hagiwara (currently a professor at the graduate school of medicine and faculty at Kyoto University,
formerly a professor at Tokyo Medical and Dental University). KinoPharma strives for R&D on novel small­moleculedrugs targeting kinases involved in various viral diseases such as viral warts, epidemic keratoconjunctivitis, andhepatitis B, as well as treatment drugs for neurodegenerative diseases such as ADs. The company is headquarteredin Chuo­ku Tokyo, and its CEO is Masafumi Kuroishi.
■ About National Institutes for Quantum and Radiological Science and Technology (QST)
The National Institutes for Quantum and Radiological Science and Technology (QST) was newly launched as a
National Research and Development Agency on 1 April 2016. QST combines the research and development
abilities of five Japanese national institutes in the fields of radiology, quantum beams and nuclear fusions to form aworld class institution in quantum science and technology research. Among these institutes, the National Institute ofRadiological Sciences (NIRS) is mainly engaged in R&D into innovative medical use of radiation and research into
the impact of radiation and radiation medicine. It is headed by President Toshio Hirano.
■ Terminology1) Tau protein
Tau protein binds to and stabilize the microtubules of neural cells, which contributes to cellular structural formationand transportation. It is already known that in various neurodegenerative disorders such as AD, tau protein undergoes
abnormal phosphorylation that results in abnormal accumulation within cells, which is considered to induce the onsetand progression of the diseases.

2) PETPET stands for positron emission tomography, a diagnostic technology. PET allows non­invasive observations (orvisualization) of biomolecular processes in the living body. The technology involves the administration of a PET
agent labeled with a specific radioisotope to patients, and the detection of gamma rays stemming from positrons
emitted by the PET agent allows the localization of the agent deep inside the body in a three­dimensional manner.

3) Amyloid βAβ is one of the main components of the pathological hallmarks that are commonly observed in AD, such as senile
plaques and cerebral amyloid angiopathy. Aβ itself has been reported to have toxic effects on neurons.

End of press release

For inquiries related to this press release, please contact:
Mr. Yuki Furuko or Mr. Kozo Eguchi, Corporate Planning and Administration Department, KinoPharma, Inc.
Tel: +81­3­6264­9604 Email: eguchi@kinopharma.com/furuko@kinopharma.com

Mr. Kunihiro Suzuki, Public Relations Section, Department of Managing and Planning,
National Institutes for Quantum and Radiological Science and Technology
Tel: +81­43­206­3026Email:info@qst.go.jp