September 6, 2019
EA Pharma Co., Ltd.
National Center of Neurology and Psychiatry

National Center of Neurology and Psychiatry and EA Pharma Co., Ltd.
Sign a Global License Agreement for OCH-NCNP1
EA Pharma Co., Ltd. (President, Yuji Matsue; Headquarters, Tokyo, Japan) (hereinafter “EAPharma”) and National Center of Neurology and Psychiatry (President, Hidehiro Mizusawa;
Headquarters, Tokyo, Japan) (hereinafter “NCNP”) have signed a worldwide exclusive license
agreement for development, manufacture and marketing for all indications of OCH-NCNP1,
which is under development by NCNP (hereinafter “OCH”).
Under the above agreement, EA Pharma pays an initial fee, milestone fees and royalties toNCNP.
OCH was designed and synthesized by Dr. Takashi Yamamura (Director, Department ofImmunology, National Institute of Neuroscience, NCNP) and his colleague by modifying thestructure of glycolipid alpha-galactosylceramide (alpha-GalCer) produced by bacteria
parasitizing marine sponge.1) In recent years, it was found that human enteric bacteria produce
analogues of alpha-GalCer, similar to OCH. Such gut bacteria-derived glycolipids are thoughtto contribute to immune homeostasis by inducing Th1 and Th2 cytokines from natural killer Tcells (NKT).2), 3) Although alpha-GalCer induces both Th1 and Th2 cytokines from NKT cells,
OCH selectively induces production of Th2 cytokines. Therefore, OCH has the therapeuticpotentials to suppress the activity of Th1 cytokines and to improve chronic inflammation
caused by excessive actions of Th1 cytokines. NCNP has conducted an investigator-initiatedPI trial for OCH with patients suffering from multiple sclerosis and now plans to proceed to PIIa.
Keio University Hospital has been conducting jointly with NCNP an investigator-initiated PI/IIclinical trial for OCH with patients with Crohn’s disease since 2016.4)
The above agreement was realized through the opportunity of introduction of OCH to EA
Pharma by Translational Research Center for Medical Innovation (TRI)* of Foundation for
Biomedical Research and Innovation at Kobe, which supports development of research seeds
in universities and other research institutes of Japan. EA Pharma and NCNP collaborate topromote development of OCH to contribute to treatment and increase of QOL of patients withintractable diseases.
End11) Miyamoto K, Miyake S, Yamamura T., A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing
TH2 bias of natural killer T cells. Nature. 2001; 413: 531-534.
2) An D et al., Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells.
Cell. 2014; 156: 123-133.
3) Wieland Brown LC et al., Production of -α-galactosylceramide by a prominent member of the human gut
microbiota. PLoS Biol. 2013; 11: e1001610.
4) Keio University and AMED initiate an investigator-initiated clinical trial to investigate the safety and efficacy of aninvestigational drug for treatment of intractable Crohn’s disease (Press release in Japanese only)
https://www.keio.ac.jp/ja/press-releases/2016/9/15/28-18435/* Translational Research Center for Medical Innovation (TRI): https://advances.tri-kobe.org/

The development of OCH-NCNP1 is supported by the following grants.
・Ministry of Health, Labour and Welfare (Japan) Research Grants.
・Japan Agency for Medical Research and Development (AMED) Research Grants.

Media Inquiries
EA Pharma Co., Ltd.

National Center of Neurology and Psychiatry.

Corporate Planning Dept.

Takashi Yamamura MD,PhDemail：contact_ea@eapharma.co.jp

Director and Chief of the Neuroimmunology
Sectionemail: yamamura@ncnp.go.jp
orGeneral Affairs Dept. Public Relations
email: ncnp-kouhou@ncnp.go.jp

2More Information
1. About natural killer T (NKT) cells and Th1/2 cytokines
Natural killer T (NKT) cells are a unique lymphocyte population that recognize glycolipid
antigen bound to CD1d. In response to antigen receptor stimulation, NKT cells immediately
secrete a large amount of bioactive substances including cytokines and chemokines. Thecytokines produced by NKT cells include Th1 cytokines (interferon gamma, TNF alpha, etc.)that strengthen cellular immunity and Th2 cytokines (interleukin-4, IL-5, IL-13, etc.) thatstrengthen humoral immunity. Th1 and Th2 cytokines mutually antagonize each other. NKTcells produce Th1 or Th2 cytokines as appropriate to maintain the lymphocyte balance andsuppress excessive immunoreaction and inflammatory response. NKT cells can be a key in awide range of disease areas including autoimmune diseases, allergic diseases, organtransplantation and immunology of infectious diseases.

2. About EA Pharma Co., Ltd. (EA Pharma）
EA Pharma Co., Ltd., a subsidiary of Eisai Co., Ltd. for gastrointestinal disease area, wasestablished in April 2016 by integration of the gastrointestinal business unit with more than 60
year’s history of the Eisai Group and the gastrointestinal business unit of the Ajinomoto Group
having amino acid as its business core. EA Pharma is a gastrointestinal specialty pharma with afull value chain covering R&D, production & logistics and sales & marketing. EA Pharma has been
actively engaged in academia-industry collaboration projects to transform the values created inJapanese academia into pharmaceutical products.
For more information on EA Pharma, please see http://www.eapharma.co.jp/en/

3. About National Center of Neurology and Psychiatry (NCNP)In NCNP, our hospital and institutions work together in research and development to overcome
mental disorders, neurological and muscular diseases, and developmental disorders with themission to use our research results for providing advanced medical services and to spread ourservices across the country.
For more information on NCNP, please see https://www.ncnp.go.jp/english/

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