August 19, 2019

Shinshu University and BrightPath Conclude Joint R&D Agreement for
CAR-T Cell Therapy for Solid Tumors
Tokyo, August 19, 2019 — National University Corporation Shinshu University and BrightPath
Biotherapeutics Co., Ltd., an immuno-oncology company, announced the conclusion of a
joint research and development agreement aiming at the clinical development of CAR-T celltherapy for solid tumors.
A cancer antigen called “HER2” is overexpressed in many cases of solid tumors. While antiHER2 antibody drugs have already been put into practical use, HER2 continues to draw
attention as a promising target antigen in cancer treatment. In cooperation with Shinshu
University, BrightPath will start preparations for an investigator initiated trial treating patientswith osteosarcoma using HER2-CAR-T cells as an investigational drug. These cells
recognize HER2 antigens, and are produced using a method established by Professor Yozo
Nakazawa, Department of Pediatrics, Shinshu University School of Medicine, AssistantProfessor Shigeki Yagyu, Department of Pediatrics, Kyoto Prefectural University of Medicine,and others.
CAR-T cells, which have been transduced with a viral vector or the like, recognize cancer
antigens via chimeric antigen receptors (CARs) and have the ability to kill cancer cells. CART cell therapy has already been approved in Japan, the US and Europe for certain
hematologic cancers, and its substantial benefits have recently been clinically demonstrated.
In the pursuit of further clinical effects, development of next-generation CAR-T cell therapy
is already in progress around the world. While its effects are evident in an expanding rangeof hematologic cancers, there is still room for improvement in the area of solid tumors.
The difficulty in using CAR-T cell therapy targeted to treat solid tumors is due to the fact thatsustained anti-tumor effects of CAR-T cells are required for them to be effective in the fierce
environment specific to solid tumors, known as the “tumor microenvironment,” where thefunctions of immune cells are suppressed. One solution to overcome this difficulty is to use
the non-viral gene transfer method established by Professor Yozo Nakazawa’s team and thenew CAR-T cell culture method jointly developed by Professor Nakazawa’s team and othergroups (joint patent pending). It is suggested that CAR-T cells created by these methods
have more sustained anti-tumor effects in comparison with CAR-T cells created by1

conventional viral methods. This new approach is therefore expected to achieve sustained
activity in the immunosuppressive tumor microenvironment and thereby exhibit greater
efficacy against solid tumors.
Shinshu University is now preparing an investigator initiated trial treating osteosarcoma, arepresentative pediatric cancer. Although recent progress in osteosarcoma treatment has
been remarkable, development of new therapeutic options is awaited in order to cure thosewith severe symptoms or distant metastases and prevent cancer recurrence. In the US,clinical trials for such cases of refractory osteosarcoma have been conducted using HER2CAR-T cells, which are created through traditional genetic modification using conventional
viral vectors. In some cases reported from those clinical trials, promising results, including
complete remission, have been observed. With the clinical concept already proven,
BrightPath expects that CAR-T cell therapy targeting HER2 antigens but using the more
durable platform technology invented by Professor Nakazawa, will broaden future
therapeutic options for such patients, and has decided to commit its support to Shinshu
University’s upcoming investigator initiated clinical trial, which is scheduled to start in fiscal
2020.
Shinshu University
Shinshu University is a national university with eight faculties (Arts, Education, Economics
and Law, Science, Medicine, Engineering, Agriculture, and Textile Science and Technology)
on five campuses, which are located in four municipalities in Nagano Prefecture (Nagano,Matsumoto, Ueda, and Minamiminowa). The university marks its 70th anniversary in 2019.
Shinshu University Hospital is the only national university hospital in Nagano Prefecture, with32 clinical departments and 707 beds. It provides safe and secure medical services as agovernment-designated advanced treatment hospital, performs leading-edge medical
practice based on state-of-the-art research achievements, and endeavors to develop next
generation international healthcare human resources.
BrightPath
BrightPath is a clinical stage biopharmaceutical company focused on the development ofnovel cancer immunotherapies to transform cancer treatment for progressive or refractorycancers that cannot be treated using conventional standard therapies. In addition to its
cancer peptide vaccines currently in clinical trials in the United States, BrightPath is actively
involved in developing cell therapies, immunomodulatory antibodies and new drugs targeted
toward cancer-specific neoantigens.
2Inquiries
Shinshu University School of Medicine
Miyuki Tanaka, Department of Pediatrics
Tel: +81-263-37-2642
E-mail: miyuki@shinshu-u.ac.jp
https://www.shinshu-u.ac.jp/english/
BrightPath Biotherapeutics Co., Ltd.
Administration Department
Tel: +81-3-5840-7697
E-mail: irpr05@brightpathbio.com
https://www.brightpathbio.com/english/index.html

Source: Shinshu University and BrightPath Biotherapeutics Co., Ltd.

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CAR-T Cell Therapy for Solid Tumors (BP2301)
Supplemental Information
August 19, 2019

Mechanism of the Anti-Tumor Effect of CAR-T Cells
A chimeric antigen receptor (CAR) is a protein designed to bind to certain tumor
antigens on cancer cells. It also contains a signal transmitting domain to activate Tcells. By transducing a CAR into a T cell, the CAR-T cell can come to recognize
tumors and exert anti-tumor effects.

1

Flow of Treatment in CAR-T Cell Therapy
An anti-tumor effect is achieved by transfecting CAR genes into T cells collectedfrom the patient’s blood, growing them in culture and returning the CAR-T cells into
the patient's body.

2Characteristics of BP2301
BP2301 is largely comprised of young memory T cells with high proliferative capacity
and long-term persistence, leading to durable anti-tumor effects.
T cell subset and differentiation

BP2301 T cell subset

Effector function (anti-tumor function) is enhanced upon T celldifferentiation, while memory function and proliferation
capacity are gradually lost.

The young memory-rich BP2301 cell subset maintains
proliferative capacity to produce cytotoxic effector T cells afteradministration (left figure), while the effector-rich CAR-T
subset has transient proliferative capacity and effector function(right figure).

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