Operating Structure

Research and Development Projects Adopted in FY2015 Research and Development Projects Adopted in FY2014 Project for Intellectual Property Strategy Promotion Organization PS,PO

This program is promoted by the Japan Agency for Medical Research and Development (AMED) in collaboration with the Ministry of Education, Culture, Sports, Science and Technology. One program supervisor (PS) and two program officers (POs) monitor the progress of the overall program, and provide instruction and advice necessary for smooth implementation. In addition to the PS and POs, eight pharmaceutical research and development (R&D) experts manage and evaluate each project.

Twenty-six research projects have been carried out thus far-17 in FY 2014 and nine in FY 2015. In addition, one project for the development of intellectual property strategy was conducted in FY2014.

PS, POs, and Experts in Pharmaceutical Research and Development for Management and Evaluation

Program Supervisor (PS)

Committee members Affiliation
Miyata Toshio Professor, Graduate School of Medicine, Tohoku University

Program Officers (POs)

Committee members Affiliation
Horiuchi Tadashi Guest Professor, School of Medicine, Keio University
Ohtaki Yoshihiro President, BioFrontier Partners, Inc.

Experts in pharmaceutical research and development

Committee members Affiliation
Okazaki Hiroshi Executive Officer, Vice President Head R&D Division; Director Translational Research Unit, Kyowa Hakko Kirin Co., Ltd.
Ochiya Takahiro Chief, Division of Molecular and Cellular Medicine, Group for Translational Research, National Cancer Center Research Institute
Kawaguchi Tsutomu External Director, Chiome Bioscience Inc.
Koumegawa Junichi Advisor, BioFrontier Partners, Inc.
Goto Toshio Program Director, Program for Drug Discovery and Medical Technology Platforms, Cluster for Industry Partnerships, RIKEN
Tsumoto Kouhei Professor, Graduate School of Engineering, The University of Tokyo
Nangaku Masaomi Professor, Graduate School of Medicine, The University of Tokyo
Miyata Mitsuru Executive Leader Writer, Nikkei Business Publications, Inc.

Message

Program Supervisor's Message

Toshio Miyata

Program Supervisor
Professor, Graduate School of Medicine, Tohoku University Miyata Toshio

Collaboration with multiple stakeholders to launch innovative biopharmaceuticals in Japan

Drug discovery and development is a good example of the type of knowledge-intensive industry that Japan is striving to cultivate. Because the market for drug development is growing as the population ages, this industry is positioned as a next-generation growth industry in the government’s Japan Revitalization Strategy. In today’s drug industry, it has become difficult to rely solely on low-molecular-weight drugs produced through the conventional method of chemical synthesis, and we must turn to biopharmaceuticals made using biotechnology. Japan, however, has been noted as being slow to venture into biopharmaceutical development compared to Western countries, and for this reason, the Ministry of Education, Culture, Sports, Science and Technology initiated a five-year "Basic Science and Platform Technology Program for Innovative Biological Medicine" in 2014. To strengthen Japan’s ability to compete in the international market, we must solve technological problems faced in this field and out-license the resulting intellectual property and knowledge to companies so that they can develop innovative next-generation biopharmaceuticals.

Japan has a high level of fundamental research, and in drug development, there have been many successes in basic research and a wealth of information acquired about potential drug targets. Various policies implemented in recent years aimed at accelerating the practical application of research have laid the groundwork for taking basic research at universities—mainly findings regarding low-molecular-weight drugs—from the drug development process through investigator-initiated clinical trials to evaluate effectiveness in humans in order to establish proof of concept (PoC). It is now possible for academic researchers, through close collaboration with contract research organizations and contract manufacturing organizations (CROs/CMOs), to be involved in the development process of a first-in-human class drug, from hit compound discovery through structural optimization, GMP synthesis and formulation, and a panel of pre-clinical GLP pharmaco-toxicological studies all the way through investigator-initiated clinical trials. Low-molecular-weight drugs can be manufactured with uniform structure and quality because they are created through chemical synthesis. Furthermore, their structure and quality are easily analyzed with the technology we currently have. This explains why academic researchers have had success in drug development and building expertise in this area with relative ease.

Biopharmaceuticals, in contrast, have a high molecular weight and much more complex structures. Parameters, such as conditions for culturing, purification, and concentration must be strictly controlled to ensure a certain standard of quality, making it difficult to ensure the equivalency of large quantities of products. (This is also clear from the difficulty of developing biosimilar generic versions of biopharmaceuticals compared with developing generic versions of low-molecular-weight drugs.) There is very little collaboration between academic researchers and CROs/CMOs that specialize in biopharmaceuticals (bio CROs), so that even if academic researchers make theoretically successful proposals for innovative biopharmaceuticals, there are major challenges in bringing those drugs to clinical trials and eventually market. Furthermore, unlike with low-molecular-weight drugs, many pharmaceutical companies have not built up sufficient experience or expertise regarding biopharmaceuticals. Biopharmaceuticals, particularly therapeutic antibodies, account for over one-third of staple products in the global pharmaceutical market. However, only a few pharmaceutical companies have brought new drugs developed in Japan to market. As this illustrates, academic researchers, bio CROs, and pharmaceutical companies (bio ventures) are building experience in this field independently of each other, so promoting ties and cooperation among these groups is an important next step.

If Japan is to create innovative next-generation biopharmaceuticals, we must do more than simply discover elemental technology, candidate drugs or new concepts; we must also identify and resolve a multitude of issues. For example, we should increase added value and improve the likelihood that candidate drugs will actually be produced by establish a forum where academic researchers, bio CROs, and bio ventures can being together their experience and expertise. Unless these steps are taken, regardless of whether Japanese universities make academic breakthroughs—which I think they are capable of doing—issues with manufacturing technology, intellectual property, pharmaceutical regulations, and communication networks will prevent us from creating innovative next-generation biopharmaceuticals.

Many promising candidate drugs discovered by academic researchers are in the the cultivation phase of development. It is at these early stages that we must provide either strong motivation or support for an exit strategy of out-licensing or commercialization. Furthermore, because pharmaceutical companies cannot license every drug candidate introduced by academic researchers, universities must cultivate those that cannot immediately be out-licensed through material optimization, quality assurance, and GLP studies in accordance with the Pharmaceutical Affairs Law, collaborating with bio CROs as necessary . Through such a process, researchers and other involved parties will develop the experience and expertise needed for low-molecular-weight drug development. Although this slightly diverges from the purpose of this program, I believe that along with tackling various challenges in research and development, it is important to discuss and implement measures to solve these kinds of issues.

Because biopharmaceuticals have a brief history compared to low-molecular-weight drugs, there remain various issues in their development. There also is, however, untapped potential for innovative drugs to be born in this field. In fiscal 2014 and 2015, we selected 26 new research and development projects in a variety of areas. All of these projects involve drug candidates or elemental technologies that have the potential of producing innovative biopharmaceuticals, so I am looking forward to seeing progress in these research projects. We are fortunate to have experts with vast experience in biopharmaceutical development join us to determine how the program is implemented. I hope we can all work together to manage the program in a flexible and productive manner.

In April 2015, the program was transferred to the auspices of the Japan Agency for Medical Research and Development (AMED) and became a pillar of the "Project for Drug Discovery and Development" strategy. We also hope to link it with other programs planned by AMED and to maintain open dialogue with regulatory authorities and private businesses such as bio ventures, bio CROs, and pharmaceutical companies. I sincerely request your support in accomplishing our goals.

Program Officers' Messages

Tadashi Horiuchi

Program Officer
Guest Professor, School of Medicine, Keio University Horiuchi Tadashi

My hopes for the "Basic Science and Platform Technology Program for Innovative Biological Medicine"

When biopharmaceuticals first emerged in the latter half of the 1990s, major Japanese pharmaceutical companies were relatively focused on developing low-molecular-weight drugs. By the early 2000s, a major gap had emerged between the biopharmaceutical development expertise of Western and Japanese pharmaceutical companies. Now that a number of biopharmaceuticals (therapeutic antibodies) and biotechnologies such as the anti-IL-6 receptor antibody, the anti-PD-1 antibody, and Potelligent Technology have been successively developed in Japan, however, it is safe to say that the gap has narrowed.

In December 2013, Ono Pharmaceutical Company submitted an application seeking approval to manufacture and distribute the anti-PD-1 antibody for treating advanced malignant melanoma, and it currently appears to be highly effective in clinical practice. The antibody is indicated for more than just malignant melanoma; it was announced that the United States Food and Drug Administration designated it as a breakthrough therapy for advanced non-small cell lung cancer. Although a series of such miraculous therapeutic antibodies have been developed in recent years, problems remain, such as high costs and injection being the only route of administration. Although improvements in production methods and reductions in the molecular weights of antibodies are being addressed as solutions to these problems, our research techniques are still insufficient, requiring that we conduct further research and development.

With nucleic acid drugs, we can now create new drug targets and develop new drugs that are completely different from those of the past. Japanese researchers publish an impressive number of papers in the field of nucleic acid chemistry, and in recent years, a number of Japanese ventures based on nucleic acid chemistry, including Bonac and Chiralgen, have been founded, turning nucleic acid research into a vibrant field. Phase I trials for two types of nucleic acid drugs developed by Japanese companies began in 2013, and several more varieties of nucleic acid drug are being administered to humans in investigator-initiated clinical studies. However, nucleic acid drugs tend to break down easily, and they must be improved through a better understanding of their pharmacokinetics and degradation pathways. And as with therapeutic antibodies, nucleic acid drug synthesis has other problems, too, such as low yield, and further research and development is needed to resolve such issues.

As described above, breakthrough biopharmaceuticals and biotechnologies are being developed in Japan and there is evidence of stronger commitment to such research and development in recent years. However, over 900 biopharmaceutical products, including vaccines, were developed in the United States in 2012. For Japan to create biopharmaceuticals at the same level as Western countries, it is essential that industry, government, and academia promote further research and development. To accelerate research and development of biopharmaceuticals, the Ministry of Education, Culture, Sports, Science and Technology launched the "Basic Science and Platform Technology Program for Innovative Biological Medicine" in 2014 as part of its Project for Drug Discovery and Development strategy. The mission of this program is to develop the underlying technology necessary for producing innovative biopharmaceuticals and to transfer this technology to companies and other entities within five years.

To achieve the goal of out-licensing within this 5-year time span, I believe it is imperative that those with industry experience in research and development evaluate and support our program’s research and development efforts by sharing their unique perspectives, which differ from those of academic researchers. I was involved in drug discovery research at a pharmaceutical company for over 30 years, mainly in low-molecular-weight drugs. Specifically, I was responsible for drug target discovery tasks such as the discovery of targets through genome research, compilation of compound libraries with hundreds of thousands of entries, high-throughput screening, protein structural analysis, structure-based drug design, and bioinformatics, as well as the design of early screening systems. I subsequently left to work at Keio University and am now involved in collaborative projects between industry, government, and academia as well as in translational research. My many years in research and development at a pharmaceutical company allowed me to forge close relationships with people involved in research and development at companies developing pharmaceuticals and diagnostics. I believe these personal connections are valuable in gaining corporate support when necessary. As Dr. Fukuzawa Yukichi once said, "Learning is no better than ignorance if you do not apply it." I hope to use my network of personal connections to proactively transfer and apply the technologies developed in our program.

The Japan Agency for Medical Research and Development (AMED) was launched in April 2015, and Japanese research in the life sciences is expected to undergo major changes as a result. If we can assure that our program is carried out well and achieves good results amid these developments, I am convinced that Japan will catch up to and even surpass Western countries in the field of biopharmaceutical drug discovery. It is also my strong hope that the results of this program will contribute to the development of drugs to treat Alzheimer’s disease, cancer, schizophrenia, and other diseases for which truly effective therapeutic drugs have yet to be discovered.

We appreciate your continued guidance and encouragement.

Ohtaki Yoshihiro

Program Officer
President, BioFrontier Partners, Inc. Ohtaki Yoshihiro

Aiming for the development of biopharmaceuticals that appeal to the world

Biotechnology has made remarkable progress in recent years and is still advancing rapidly, resulting in the accumulation of evidence on whole-genome sequences with the use of next-generation sequencers, identification of new target molecules, elucidation of molecular mechanisms underlying the actions of drug candidates, and development of genome editing technology. There are growing expectations that these technologies will enable the development of unique biopharmaceuticals with new mechanisms. Amid such expectations, biopharmaceutical development has become a highly competitive field around the world. Japan must keep up with the rapid increase in the proportion of biopharmaceuticals among innovative pharmaceuticals, now a worldwide trend .

Japan has continued to make significant contributions to the world in fundamental research, including identifying target molecules. However, clinical application of these findings has often been carried out by companies in the West, indicating the lack of an established system supporting actual product development in Japan.

In order to survive global corporate competition, it is important to possess the ability to conduct research and development that result in internationally competitive biopharmaceuticals, and further, to promptly bring newly developed products to market. The product development stage before commercialization requires strict progress management and strategies such as intellectual property strategies and schedule-oriented project management, in addition to the accumulation of solid evidence, since we are in competition with the rest of the world. In other words, we must establish a support system that clearly indicates an exit strategy and seamlessly provides support from the basic research stage of “seeds” to the commercialization stage of biopharmaceuticals. In fact, this is the reason why the Ministry of Education, Culture, Sports, Science and Technology launched the “Basic Science and Platform Technology Program for Innovative Biological Medicine” in 2014.

The ultimate goal of our program is to develop basic technologies in academia, the outcomes of which are then swiftly transferred to industry for commercialization, with a maximum transfer time of 5 years.

To accomplish this goal, academia must produce data of sufficient quality and quantity to serve as a solid foundation for further development in industry within an appropriate research period. More precisely, academia must provide reliable data so that time is not wasted by pharmaceutical companies on data reproducibility tests. For that purpose, academics must be fully informed of the process of pharmaceutical development. In our program, a program supervisor (PS), two program officers (POs) and eight experts in drug discovery and development are assigned to a management group. Together with academic researchers, we will discuss the design and types of tests required for efficient technology transfers to pharmaceutical companies. This is the first step toward a Japan-wide system that will enable the continuous production of biopharmaceuticals.

In April 2015, the program was transferred to the Japan Agency for Medical Research and Development (AMED), which conducts several pharmaceutical-development-related programs simultaneously. We hope to collaborate with its other programs and aim to develop biopharmaceuticals that appeal to the world.

Your continued support is greatly appreciated.

Project for Intellectual Property Strategy

Development of intellectual property and exit strategies for creating innovative biopharmaceuticals

Associate Professor, Graduate School of Medicine, Tohoku UniversityAkahori Koji

The aim of this program is the technology transfer of 26 projects implemented in this program to companies, which requires support in formulating intellectual property strategies and exit strategies.

This project brings together specialists in intellectual property and pharmaceutical development to provide such support.

We assess intellectual property strategies based on analyses of individual research and development (R&D) projects’ progress and granted patents. Research on surrounding technologies is performed when necessary. After consulting with the Japan Agency for Medical Research and Development (AMED), a program supervisor (PS), two program officers (POs), and eight experts in pharmaceutical R&D make recommendations to each R&D project and the corresponding intellectual property division.

Advice on exit strategies are provided to each R&D project based on analyses of progress and validity of commercialization, and the results of market research and assessment. Providing advice on corporate collaboration and pharmaceutical regulations is another important element of exit strategies.

This project continues to refine intellectual property strategies and exit strategies, and to assist the smooth the transfer of R&D outcomes to companies and other entities.