Mie University

Kusatsu/Shiga, Japan — April 18, 2019 – Takara Bio Inc. (Takara Bio) announces that it has started the joint research on new development of CAR gene therapy with a group led by Dr. Hiroshi Shiku, Professor at Mie University Graduate School of Medicine (Mie University). CAR gene therapy is to take the autologous lymphocytes from a patient, transduce CAR gene boosting the ability to attack cancer, and introduce the CAR-transduced lymphocytes back into the patient. CD19・CAR gene therapy known as a kind of CAR gene therapy shows favorable therapeutic efficacy against some blood cancers, and is being processed for marketing approval in the US, Europe and Japan. This joint research challenges for CAR gene therapy with focuses on the persistence effect on therapy (relapse prevention) and the expand indications to solid cancer, apart from blood cancer. Specifically, it is performed by the alteration in gene structure related to two functional domains: (i) “antibody” specific to cancer antigen and (ii) “signal transduction” involved in attack capability on the CAR gene, with evaluation in culture cells and/or laboratory animals for the effect. It allows the better understanding of the effect on: (i) antibody domain recognizing CEA (cancer antigen expressed significantly in solid cancer) and (ii) our original technique GITR owned by Takara Bio and Mie University (protein involved in life lengthening of T cells and attack persistence). Takara Bio and Mie University have track records in co-developing for NY-ESO-1・siTCR™ gene therapy and are going forward in co-developing this CAR gene therapy newly as well. Takara Bio is making further efforts to address the unmet medical needs through developing cancer immune and gene therapy such as CAR gene therapy and realizing its commercialization. Copyright © Takara Bio Inc. All Rights Reserved.

Otsu/Shiga, Japan – June 10, 2015 - Takara Bio Inc. announced that a patent regarding siTCR vector, one of core techniques of Takara Bio’s gene therapies was granted by United States Patent and Trademark Office. The siTCR technique minimizes the expression of endogenous TCRs by RNA interference, and allows for obtaining more lymphocytes that express the target TCR. The technique is thought to reduce the risk of side effects and improve effectiveness. The patent granted this time was applied jointly with Mie University and Takara Bio. Takara Bio further facilitates clinical development of siTCR gene therapies based on its proprietary siTCR vector technique, aiming at commercialization of the therapy by fiscal 2021. Copyright © Takara Bio Inc. All Rights Reserved.

Otsu/Shiga, Japan – March 3, 2014 – Takara Bio Inc. announced today that it has obtained a project grant from the Japan Science and Technology Agency (JST). On the same day, JST publicly disclosed on its website that Takara Bio’s TCR gene therapy projects would receive funding through JST’s A-STEP program (Adaptable & Seamless Technology Transfer Program through Target-driven R&D) for FY 2014. The JST has acknowledged the vast potential of Takara Bio’s TCR gene therapy program because of our ground breaking technological innovations in the field. The main mechanism of action for TCR gene therapy is via gene-transduced lymphocytes, which acquire the capability to specifically recognize and attack cancer cells and eliminate them. TCR genes that are capable of recognizing cancer antigens are transduced into the patient’s own lymphocytes, which are then re-infused into the patient. Our MAGE-A4 antigen-specific TCR gene therapy and NY-ESO-1 antigen-specific TCR gene therapy have both been selected for the A-STEP program. These therapies have been developed in collaboration with Mie University. The Japanese government is instituting a wide range of measures as an important governmental policy to accelerate the commercialization of the regenerative medicine, where the Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Ministry of Economy, Trade and Industry (METI) and the Ministry of Health, Labour and Welfare (MHLW) collaborate tightly to seamlessly advance the practical application and commercialization of regenerative medicine from basic research through clinical trials. JST, one of the core institutions responsible for the implementation of science and technology policy in Japan under the umbrella of MEXT, designs several types of the competitive funding programs called A-STEP, where the optimal R&D funding and R&D period will be offered depending on the R&D phase and objectives of each particular project. Takara Bio’s TCR gene therapy projects were chosen as the final R&D phase for practical application of drug development. With this governmental support, Takara Bio aims to advance its TCR gene therapy projects with further effectiveness and efficiency. [ About Takara Bio Inc. ] Takara Bio Inc. is an innovative biotechnology company based in Shiga, Japan. As a world leader in biotechnology research and development, Takara Bio was the first company to market PCR technology in Japan and is also the developer of the RetroNectin® reagent, which is a world-standard in gene therapy protocols. In addition to providing research reagents and equipment to the life science research market, Takara Bio has active research and product development activities in the fields of gene and cell-based therapy, and agricultural biotechnology including functional food and mushroom production businesses; and is committed preventing disease and improving the quality of life for all people through the use of biotechnology. Through strategic alliances with other industry leaders, the Company aims to extend its reach around the world. More information is available at http://www.takara-bio.com. Copyright © Takara Bio Inc. All Rights Reserved.