May 09, 2019
Ohara Pharmaceutical Co., Ltd.
Patent Assignment Agreement on Novel Sarcoma Treatment
Ohara Pharmaceutical Co., Ltd. (Head office: Shiga, Japan; CEO: Seiji
Ohara; hereinafter, “Ohara”) has entered into a patent assignment
agreement concerning the novel compound ZSTK474 (Development No.
OP-11) with Zenyaku Kogyo Co., Ltd. (Head office: Tokyo, Japan; CEO:Koichi Hashimoto; hereinafter, “Zenyaku”) dated April 19, 2019.
In this agreement, Ohara has acquired the worldwide patent ofZSTK474 and will inherit the development from Zenyaku. Ohara will makean upfront payment and milestone payment to Zenyaku.
ZSTK474 (Development No.: OP-11) is a novel anticancer compound
synthesized by Zenyaku. At the Cancer Chemotherapy Center, JapaneseFoundation for Cancer Research (Tokyo, Japan; hereinafter, “JFCR”), it
has been shown to be a potent inhibitor of phosphatidylinositol-3 kinase(PI3 kinase, PI3K), an intracellular signaling factor that plays a central
role in cancer growth and survival.(1)Phase I clinical trials were conducted in Japan and the United States.
Two of four sarcoma patients achieved stable disease in a clinical trial in
the US, so the effect on sarcoma has attracted attention.(2) In addition,
in reverse translational research at JFCR, in vitro tests and in vivo tests
were performed using various sarcoma cells. As a result, ZSTK 474 has
shown antitumor activity on sarcomas, in particular Ewing's sarcoma,alveolar rhabdomyosarcoma, and synovial sarcoma cell lines, which arepositive for a chromosomal translocation.(3)Most of these sarcomas occur at a young age. Chemotherapy is themain treatment for metastasis, advanced cancer, and recurrent cancer,
but the available anticancer drugs are limited, and the development ofnew sarcoma therapeutics is of high interest.
Ohara will advance the clinical development so that ZSTK474(Development No. OP-11) can be delivered as a new treatment option tomeet the unmet medical needs of sarcoma patients.

Ohara Pharmaceutical Co., Ltd.

1. Yaguchi S, Fukui Y, Koshimizu I, Yoshimi H, Matsuno T, Gouda H, Hirono S, Yamazaki K, Yamori
T. Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. J Natl Cancer
Inst. 2006; 98: 545-56. doi: 10.1093/jnci/djj133.
2. Lockhart AC, Olszanski AJ, Allgren RL, Yaguchi S, Cohen SJ, Hilton JF, Wang-Gillam A, Shapiro
GI. Abstract B271: A first-in-human Phase I study of ZSTK474, an oral pan-PI3K inhibitor, inpatients with advanced solid malignancies. Molecular Cancer Therapeutics. 2013; 12: B271-B.
doi: 10.1158/1535-7163.targ-13-b271.
3. Namatame N, Tamaki N, Yoshizawa Y, Okamura M, Nishimura Y, Yamazaki K, Tanaka M,Nakamura T, Semba K, Yamori T, Yaguchi S, Dan S. Antitumor profile of the PI3K inhibitor
ZSTK474 in human sarcoma cell lines. Oncotarget 2018; 9(80):35141-35161. doi:
10.18632/oncotarget.26216.

[About Ohara Pharmaceutical Co., Ltd.]
Ohara Pharmaceutical Co., Ltd. engages both in orphan drug andgeneric drug business so that we can contribute to the creation of asociety where everyone’s wishes are realized. Its 3-year “Challenge 2020”
business plan commenced in fiscal 2018, and one key objective of thisplan is to challenge and address unmet medical needs. The company
develops and markets orphan drugs mainly in the field of pediatriconcology and also operates an innovative generic drug business paying
particular attention to prevent medical accidents. Ohara PharmaceuticalCo., Ltd. plans to further expand these businesses into emerging
countries, primarily in the Asian region. Currently, the environment for
healthcare treatment options and treatment results are improving. In thisregard, at Ohara, we are aiming to provide not only treatment options
for patients, but also aiming to identify and develop innovative tools toimprove the quality of diagnosis, prevention and after care in an effort tobecome a Total Healthcare Solution company for patients.
[About Zenyaku Kogyo Co., Ltd.]
Since its foundation, Zenyaku Kogyo Co., Ltd. has made constantefforts to develop original medicines based on the drug discovery
philosophy of "Zenyaku does not imitate, but creates a drug that is one
step ahead, we create efficacy, and serve with efficacy." Layering in thefield of OTC pharmaceuticals, on which we have focused since ourfoundation, we have made efforts to create pharmaceuticals that haveboth superior efficacy and high safety as our first mission, taking
advantage of the technologies developed over many years. Furthermore,in the skin care and health food fields, we apply our drug development
capabilities to provide products that meet the various needs of ourOhara Pharmaceutical Co., Ltd.

customers. In the field of medical pharmaceuticals, we are working on
the development of innovative new drugs for cancer and intractablediseases, using the latest technology. Zenyaku will continue to contributeto society by combining support for people's health promotion with OTC
drugs and producing results that contribute to advanced medical care.

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

Ohara Pharmaceutical Co., Ltd.