Advancing the Frontiers of Cell and Gene Therapy – An Interview with Dr. Shin Kawamata

Japan is one of the pioneers of regenerative medicine in the Asia-Pacific region, with analyses suggesting that the market for related sectors (including cell and gene therapy) may surge from ¥25 billion in 2020 to ¥850 billion in 2030. Cyto-Facto Inc., established in October 2022, is also an emerging player in Japan’s cell therapy industry.

As the first spin-off company out of the Foundation for Biomedical Research and Innovation at Kobe (FBRI), Cyto-Facto is the first fully commercialized cell and gene therapy CMO/CDMO start-up in the Kobe Biomedical Innovation Cluster (KBIC), the largest biomedical cluster in Japan. It is also the first Asian company to manufacture commercial CAR-T products under the PIC/S GMP standard. Starting from April 2023, Cyto-Facto took over the operation and team of the Research and Development Center for Cell Therapy (RDC) at FBRI. Besides conducting research on the quality standards for cell preparations used in cell and gene therapy, the company also produces cell-based products commissioned by domestic and foreign pharmaceutical manufacturers to meet healthcare industry needs.

GeneOnline is honored to have Shin Kawamata, MD, PhD, founding director of RDC and current CEO of Cyto-Facto, for an interview. Dr. Kawamata, who served at FBRI from 2002 to 2014 and became the director of RDC in 2015, is an expert in cell and gene therapy in Japan. Since 2021, he has also become the co-chair of the iPSC Joint Committee at the International Society for Cell and Gene Therapy (ISCT). In this interview, he discussed the development of the biotech industry in the Kobe region, along with the progress, challenges, and prospects of cell and gene therapy research in Japan.

Related article: Current Trends of iPSC Manufacturing and Clinical Applications – An Interview with Professor Xianmin Zeng 

Exploring the Landscape of Regenerative Medicine and Synthetic Biology

Dr. Kawamata opened the conversation by highlighting the broad applications and research areas in regenerative medicine and gene therapy. He emphasized the versatility of induced pluripotent stem cells (iPSCs), with a particular focus on their ability to differentiate into neurons. This breakthrough opens doors for research and treatments related to neurological diseases.

As the innovation arm of the City of Kobe, KBIC hosts about 370 biomedical companies, academic institutions, and top-notch medical research institutes (including FBRI), as well as some of the region’s most prestigious hospitals. Notably, at least 85 biotech start-ups have been established at KBIC to date and Dr. Kawamata highlighted several promising ones in the fields of regenerative medicine and synthetic biology during the interview. Examples include Synplogen, a biofoundry that provides DNA synthesis and DNA library construction services for DNA sequencing and gene therapy product development, BioPalette, whose proprietary genome editing technology enables the development of microbiome therapies, and Bacchus Bio Innovation, a start-up company that specializes in the production of carbon-neutral bioproducts using microorganisms such as E. coli and yeast.

Another prominent company in KBIC mentioned was Vision Care Inc., founded by the team that achieved the world’s first clinical application of iPSCs. The start-up company founded by the Kobe Eye Center is dedicated to the development of treatments for retinal diseases. A crucial aspect of their work involves the use of adeno-associated viruses (AAV) to deliver gene therapeutics to eye cells for vision restoration.

An Ecosystem Approach for Bridging the Gap Between Industry and Research

One distinctive aspect of Cyto-Facto’s strategy is to contribute to the growth of the biocluster in the Kobe region, both as a service provider and a designer. According to Dr. Kawamata, Cyto-Facto positions itself as a manufacturer and software company rather than a traditional research institution, “We are more like a manufacturing-oriented company. The reason is that the FBRI has a mission to support a biocluster. Not individual small players, I think it is a supporter of the biocluster as a whole.” 

Dr. Kawamata also stressed that Cyto-Facto’s mission extends beyond academia, aiming to support a comprehensive and self-sufficient ecosystem by setting up top-tier manufacturing facilities and collaborating with different stakeholders including inspection companies, logistics companies, clinical testing companies, and human resource agencies. He opined that biotech companies should not rely only on government fundings and subsidies, but it is also very important to establish self-sustaining relationships with industrial partners.

Instead of merely serving individual doctors or researchers, Dr. Kawamata pointed out that Cyto-Facto embraces a global vision and aspires to become a key player in the biocluster, partnering with international pharma companies to achieve industrialization and advancing cell and gene therapy on a global scale. This holistic approach not only contributes to the growth of Japan’s biotech industry but also provides economic benefits to the local community.

Current Challenges and Cell and Gene Therapy

When asked about challenges of the cell and gene therapy field, Dr. Kawamata touched on the complexity of these novel modalities and the need to specify eligible patients. Besides, with the applications of iPSCs as examples, he expressed reservations about the current feasibility of regenerative medicine, citing its time-consuming and costly nature. From an economic perspective, it is still highly difficult to implement iPSC-derived cell therapies in a wider context, which is why he stressed that efforts should be made to ensure that iPSCs for research and applications are of high quality and available domestically and globally.

Also, he pointed out that sterilization processes for cell and gene therapies have not yet matured, which might present a significant hurdle for process validation. Additionally, given the fundamental differences between small molecule compounds and cell preparations, quality control for cell therapies would be much more difficult than for traditional medications. To overcome these obstacles, Dr. Kawamata highlighted the importance of digitalization and data sharing with pharma companies and clinical sites, stepping out of the “black box” due to the lack of documentation and ensuring all aspects of manufacturing are transparent and traceable. He suggested that such transparency is essential for gaining the trust of pharma companies and regulatory bodies.

Transforming Cell Manufacturing Processes Through Technology and Automation

Currently, variations in cell characteristics (size, morphology, potency, etc.) and manufacturing processes result in heterogeneous cell products, necessitating thorough verification at each shipment which hinders industrialization. Besides, reliance on manual handling of paper-based documents often leads to high costs and inaccuracies. With this in mind, the company provides a smart cell processing system by developing and introducing various smart technologies such as the Internet of Things (IoT), AI, and automation, with the aim of achieving the concept of quality by design (QbD). 

Cyto-Facto’s QbD-based solution digitizes quality control data, creating electronic batch records that integrate with internal data like inventory control and scheduling, as well as external data such as supply chain and clinical outcomes, thereby streamlining the cell manufacturing process. The company has also developed an all-in-one module that includes enterprise resource planning, manufacturing execution system and laboratory management information system. Starting with the in-house implementation of the new system, Cyto-Facto’s goal is to bring it to domestic and overseas biopharma companies and CDMOs, laying the groundwork for standardization of cell manufacturing processes at a global level.

Unlocking the Future of Cell and Gene Therapy

According to Dr. Kawamata, the future of cell and gene therapy relies on the integration of a wide range of technologies, including gene editing, gene introduction, differentiation of genes, tissue engineering, robotics and advanced analytical methods. He also shared his belief that only by embracing digitization and innovative approaches can the industry flourish.

As a concluding remark, Dr. Kawamata stated that Cyto-Facto has a vision that transcends national boundaries. Regarding global collaborations, he expressed his interest in pursuing closer ties with Taiwan, acknowledging that both regions have their own strengths and specialties that could enhance each other. He envisioned a collaboration that could set a common standard and expand globally, benefitting not only biotech companies and research institutions in Japan and Taiwan, but also the global market as a whole.

Author

Richard Chau