June 21, 2018
Ohara Pharmaceutical Co., Ltd.
License Agreement on Novel Liver Cirrhosis Treatment

Ohara Pharmaceutical Co., Ltd. (Head office: Shiga, Japan; CEO: Seiji Ohara;hereinafter, “Ohara”) has entered into a license agreement dated May 24, 2018
concerning the novel compound PRI-724 with PRISM Pharma Co., Ltd. (Headoffice: Kanagawa, Japan; President &CEO: Dai Takehara; hereinafter, “PRISM”).
Following the execution of this agreement, Ohara obtained the exclusive rightto develop, manufacture and market injectable forms of PRI-724 for liver cirrhosis
and other fibrotic diseases in Japan, as well as a first refusal right for the Asianregion. Ohara will also pay PRISM an upfront payment, development milestone
fees and sales-based royalty payments for PRI-724.
Below is a summary of the background to the consummation of this license
agreement between Ohara and PRISM:
Approximately 60% of liver cirrhosis cases in Japan are caused by hepatitis Cvirus (HCV) infections. In recent years, we have observed an increase in the useof direct-acting antiviral agents, which is making it possible to eliminate HCV.
However, the improvements of fibrosis following the elimination of HCV still takes
significant time, during which time many patients’ QOL is significantly
compromised due to complications such as carcinogenesis.
Amid the current absence of any approved drugs for the treatment of hepatic
fibrosis or cirrhosis, PRI-724 was shown to have an inhibitory effect on thedevelopment of fibrosis and a fibrolytic effect on HCV liver cirrhosis based on an
investigator-initiated study conducted at the Tokyo Metropolitan Cancer andInfectious Diseases Center Komagome Hospital. The study was conducted withthe support of the Infectious Disease Practical Research Project (ResearchProgram on Hepatitis) under the Acceleration Transformative research for
Medical innovation (ACT-M) Basic Scheme sponsored by the Japan Agency for
Medical Research and Development (hereinafter, “AMED”).
These findings demonstrate a possibility to contribute to the prognosis ofpatients with liver cirrhosis, therefore Ohara decided to develop PRI-724 with theexpectation that it will provide an innovative treatment option for patients with livercirrhosis and other fibrotic diseases.
An investigator-initiated study is expected to commence during the current
fiscal year and will primarily be conducted at the Tokyo Metropolitan Cancer andInfectious Diseases Center Komagome Hospital, with development support

Ohara Pharmaceutical Co., Ltd.

provided by Kyushu University Center, as Seeds C in the AMED Translational
Research Strategic Promotion Program. Ohara plans to continue thedevelopment efforts initiated by PRISM for PRI-724, and is supported by many
Japanese medical institutions, and will make efforts to promptly obtain themarketing authorization for PRI-724 for the treatment of liver cirrhosis caused byhepatitis B and C viruses infection.
Ohara is actively growing its development pipeline to address unmet medical
needs in Japan, and this strategic alliance with PRISM is part of these efforts.
Ohara will accelerate the development of PRI-724 products such that treatment
options can be provided to patients suffering from this intractable disease.

[About Ohara Pharmaceutical Co., Ltd.]
Ohara Pharmaceutical Co., Ltd. is one of the few Japanese pharmaceuticalcompanies that engage in both orphan drug and in generic drug business. Its 3year “Challenge 2020” business plan commenced in fiscal 2018, with one key
objective of this plan being to challenge and address unmet medical needs. Thecompany develops and markets orphan drugs mainly in the field of pediatriconcology and is also operates an innovative generic drug business which takes
careful consideration to prevent of medical accidents. Ohara Pharmaceuticalplans to further expand these businesses into emerging countries, primarily in theAsian region.

[About PRISM Pharma Co., Ltd.]PRISM Pharma Co., Ltd. is a venture company that owns a drug discovery
basis consisting of a library of low-molecular new drug candidate compounds that
inhibit protein-protein interactions (PPIs), constructed by utilizing peptidomimetic
compound synthesis technology that was developed independently by thecompany. PRISM Pharma aims to discover unprecedented therapeutic agents for
intractable diseases by regulating intracellular signal transduction, which had
been difficult before, using its own low-molecule compounds. The company’s
future policy is to work on the creation of a new pipeline for a new target following
PRI-724, to treat more diseases by making active use of its own drug discovery
basis.
For details, please visit: http://www.prismbiolab.com/[About PRI-724]
PRI-724 is a compound created by PRISM Pharma Co., Ltd. It is a CBP/beta-Ohara Pharmaceutical Co., Ltd.

catenin antagonist that inhibits the activation of the Wnt/beta-catenin signaling
pathway. PRI-724 was originally developed as an anticancer drug, but a study at
the Tokyo Metropolitan Institute of Medical Science using a liver cirrhosis mousemodel independently developed by the institute confirmed that PRI-724 has
antifibrotic effects showing improvement in liver histology. Based on thesefindings, an investigator-initiated phase I clinical trial has been completed inpatients with liver cirrhosis in Japan, at the Tokyo Metropolitan Cancer andInfectious Diseases Center Komagome Hospital, with the support of the Japan
Agency for Medical Research and Development (AMED).

[About AMED]
Under the “Plan for the Promotion of Medical R&D” established by the national
government, AMED promotes R&D mainly based on nine integrated projects
covering drug discovery and development, regenerative medicine, cancer, etc.
By consistently conducting R&D from basic research through practical application,
AMED aims to deliver its products to patients as soon as possible.
For details, please visit: https://www.amed.go.jp/. Please direct your inquiries onAMED programs to:Acceleration Transformative research for Medical innovation (ACT-M) Basic Scheme
Divisionof

Industrial-Academic

Collaboration,

DepartmentofIndustrial-Academic

Collaboration
TEL: 03-6870-2214 E-mail: sangaku-i@amed.go.jp
Infectious Disease Practical Research Project (Research Program on Hepatitis)
Contact for Research Program on Hepatitis, Division of Infectious Disease Research,
Department of Research Promotion
TEL: 03-6870-2225 E-mail: hepatitis@amed.go.jp

Translational Research Strategic Promotion Program
Division of Clinical Research and Trials, Department of Clinical Research and Trials
TEL: 03-6870-2229 E-mail: rinsho-kakushin@amed.go.jp

Contact details for inquiries regarding this issue:
Takahiro Iyo, Representative Executive Director and CFO
Yutaka Hayakawa, D.V.M,Ph.D., R&D Division Managing Executive Officer
Ohara Pharmaceutical Co., Ltd.
TEL: 03-6740-7701 FAX: 03-6740-7702

Ohara Pharmaceutical Co., Ltd.