Kusatsu/Shiga Japan – April 9, 2018 – Takara Bio Inc (Takara Bio), announced today that it has entered into an agreement with Otsuka Pharmaceutical Co., Ltd, (Otsuka) for domestic co-development and exclusive sales of NY-ESO-1 siTCRTM gene therapy product (TBI 1301, TBI-1301-A) and CD19 CAR gene therapy product (TBI 1501) as of April 9, 2018.

 

 Under the agreement, both companies will aim cooperatively for the early manufacture and sales approval of two therapeutic products in Japan. Takara Bio is responsible for manufacturing and quality control of the two therapeutic products, investigational products, while Otsuka is responsible for clinical trials, other clinical studies, regulatory submissions for manufacture and sales approval, and safety data collection of the products. After acquisition for manufacture and sales approval, Takara Bio and Otsuka are exclusively responsible for manufacturing and selling in Japan, respectively. There are no limitation on the target indications in the agreement. Otsuka also holds a right of first refusal for nine Asian countries outside Japan.

  

 Takara Bio will receive certain upfront and milestone payments from Otsuka depending on the achievement of certain development based on the execution of the agreement. Takara Bio will supply Otsuka with the products under certain financial condition.  As for NY-ESO-1 siTCRTM gene therapy product, Takara Bio will receive milestone payments upon the achievement of target sales in addition to the running royalty on Net Sales. Above up front and milestone payments will be up to a maximum total amount of around 6.3 billion yen.

 

 Masanobu Kimura, Board of Director and President of Gene Therapy Unit of Takara Bio comments that the cooperation with Otsuka having broad experience in clinical development, pharmaceutical affairs and sales of pharmaceutical products will contribute to the development, commercialization and value maximization of the therapeutic products. We are convinced of further progress on the effective development, aided by the benefit that especially NY-ESO-1・siTCRTM gene therapy product has been designated as a product under “SAKIGAKE Designation System” (prioritized review) by the Ministry of Health, Labour and Welfare on March 27, 2018.

  

 Toshiki Sudo, Executive Director, Research and Otsuka Board member noted that, “We are striving to develop innovative products that contribute to the health of humankind around the world, a part of which is co-development cooperation with Takara Bio. We know from our collaboration with Takara Bio on their oncolytic virus HF10 that they have highly advanced biotechnologies and manufacturing facilities dedicated to cell therapy. We aspire jointly to advance biologics research including gene and cell therapy to satisfy currently unsatisfied medical needs.”

 

 Takara Bio plans to disclose financial budget for fiscal year ending March 2019 at the time of a disclosure of the consolidated financial statements ending March 2018 scheduled for May 11, 2018.

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1.About Otsuka Pharmaceutical Co., Ltd.

Company Name

Otsuka Pharmaceutical Co., Ltd.

Head Office

2-9, Kanda Tsukasa-machi, Chiyoda-ku, Tokyo 101-8535, Japan

President

Tatsuo Higuchi

Business Description

Manufacturing, distributing, exporting, and importing of pharmaceuticals, clinical testing equipment, medical device and equipment, food products, cosmetics

Capital

20 billion yen

Date Established

August 10, 1964

Principal Shareholder

Otsuka Holdings Co., Ltd.

Regarding domestic development and sales of oncolytic virus HF10, Takara Bio has an exclusive licensing agreement with Otsuka in December 2016.

2. Glossary

NY-ESO-1siTCRTM gene therapy product

TCR which recognizes NY-ESO-1 antigen, a tumor antigen, is transduced ex-vivo to lymphocytes (T cells) of patients with cancer, and the gene-modified lymphocytes are subject to the efficient expansion culture and infused back to the patients as a therapeutic product. It acquires the capability to specifically recognize and attack cancer cells and eliminate them. When transducing TCR gene to lymphocytes, the siTCR vector technique minimizes the expression of endogenous TCRs and allows for obtaining more lymphocytes that express the target TCR. The product for TCR gene therapy based on Takara Bio’s proprietary siTCR vector technique is named siTCRTM gene therapy products. Takara Bio is currently conducting Phase I/II targeting synovial sarcoma in Japan. Further, it has been designated as a product under the “SAKIGAKE Designation System” by the Ministry of Health, Labour and Welfare on March 27, 2018.

 

TCRT Cell Receptor

TCR is a glycoprotein expressed on lymphocytes (T cells) and acts at the time of recognizing of tumor antigen by lymphocytes.

 

Synovial sarcoma

Synovial sarcoma is one of aggressive soft-tissue tumors associated with malignancy and with patterns of regional and distant metastasis and carries a poor prognosis. The high incidence of NY-ESO-1 antigen expression is seen in cases of synovial sarcoma, and its expression is relatively uniform throughout tumor tissue and is abundantly observed per cell.

 

CD19CAR gene therapy product

CAR which recognizes CD19, a protein (antigen) expressing on the surface of B-cell of B-cell lymphoma involved in Acute Lymphoblastic Leukemia, is transduced ex-vivo to lymphocytes of patients, and the gene-modified lymphocytes are infused back to the patients for the cancer therapeutic purpose. Takara Bio is currently conducting Phase I/II clinical trial targeting adult acute lymphoblastic leukemia in Japan.

 

Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia is attributed to the abnormality occurring during the maturation stage from  hematopoietic stem cell  to lymphocytes and is one of leukemia, resulting from rapid growth of the tumorigenic cells which were supposed to be lymphocytes under normal condition.