Open Innovation

Bayer Innovation Center Japan

Creating new opportunities for joint research and partnerships in Japan

Tokyo, capital of Japan: The high-tech nation is among the most highly educated countries in the world. In 2014, Japan took first place worldwide for the ratio of international patents and applications filed relative to its population. It ranked 2nd on the global list for company spending on research and development, 2nd for R&D expenditure per capita, and is considered among the global leaders in stem cell research. Well in line with that, the country consistently churns out a high volume of quality research, some of which has proven truly groundbreaking. On one index, however, the Land of the Rising Sun fared less well - it ranked only 16th for university - industry collaboration.

“Internal efforts are not enough - partnering is necessary,” stated Prof. Hanno Wild, Head of Candidate Generation and External Innovation
at Bayer, during his keynote speech at an open symposium held at the University of Tokyo on May 31. “Partnering along the whole value chain is a key element of our innovation strategy,” he added.

Among Bayer’s efforts to reach out to external researchers in Japan is the Grants4Targets program, a global crowd-sourcing initiative that he said has been particularly successful in Japan; no other country was awarded as many grants in 2016. “The high success rate of proposals from Japan underlines the outstanding novelty and scientific quality of applications from Japanese scientists.”

Professor Hodaka Fujii, M.D., Ph.D., Hirosaki University Graduate School of Medicine as well as Chief Executive Officer of Epigeneron, LLC, tends to his cell cultures. Aside from being a globally recognized scientist and well published author, he is a recipient of sponsorship through Bayer’s Grants4Targets initiative. “Grants4Targets is an open innovation movement. What is interesting and unique about G4T is that Bayer can support not only by funding research but also they can provide some of the resources to develop drugs. I found the culture at Bayer to be very collaborative; the Bayer culture is about win-win.”

“Biology is Method” is a guiding principle for Dr. Fujii: “In biology, developing new technologies can boost and revolutionize research.”

To help drive scientific innovation, Dr. Fujii’s work focuses on the development of novel biological technologies, and he has done so with great success. In 2013, his laboratory created the enChIP method, an innovation that allows to easily isolate specific genomic regions and to identify associated proteins, RNAs and other genomic regions. “I believe that enChIP will markedly accelerate research of regulation mechanisms of genome functions in the hopes of developing drugs against intractable diseases.”

“Innovation is the key to scientific progress,” stressed Prof. Masuhiro Kato, Translational Research Initiative, University of Tokyo in his presentation at Bayer’s ‘Frontiers of Drug Discovery’ symposium. He went on to outline the many hurdles academia face between the earliest stages of setting research targets and acquiring funding, to the final goal of bringing new compounds into clinical trials. In doing so, he identified seven key problem areas and presented suggestions for both sides to help overcome them. Among other, he stressed the importance of earlier and closer interaction between companies and academia to facilitate industry collaboration with maximum success. “The fusion of intellect should thereby lead to a co-creation of value.”

“Today’s pharmaceutical companies need highly specialized knowledge and technology in order to produce a constant stream of innovative drugs, but it is hard for a single company to do it alone,” explains Dr. Shunichi Takahashi, Head of the Bayer Open Innovation Center Japan (ICJ). As the development of cancer therapies has often proven unsuccessful, innovative cancer drug research today needs to invest into a variety of innovative therapeutic approaches. Likewise, the range of drug therapies is expanding beyond chemical compounds and includes protein and antibody therapies, and Bayer is constantly looking for partners to combine their own drug discovery expertise with cuttingedge research and technologies of universities and startups.

Established in 2014, the task of the ICJ is to help identifying those potential research cooperation projects in Japan that can contribute towards an understanding of disease mechanisms in areas of considerable unmet medical need, and which can advance the development of innovative treatments for these diseases. “In fact, more than 60 percent of a big pharma company’s pipeline derives from outside sources or joint research,” emphasizes Dr. Takahashi. During a short break at the symposium in Tokyo, ICJ Alliance Managers Dr. Tetsuya Kurihara and Dr. Taruho Kuroda, Head of ICJ Dr. Shunichi Takahashi, and ICJ Alliance Manager Dr. Koji Yashiro (from left to right) discuss next steps on the busy program agenda.

Always looking to foster collaboration in Japan, Tetsuya Kurihara, Dr. Hans Lindner, Head of Global External Innovation and Alliances at Bayer, and Dr. Shunichi Takahashi visit RIKEN, Japan's largest comprehensive research institution. Bayer wants to expand its network of university research centers and venture capitalists in Japan using the ICJ as a key driver.

Center for Developmental Biology at RIKEN’s Kobe Campus: Hazuki S. Hiraga, Science Communicator at RIKEN, explains some of the ongoing research to Dr. Hans Lindner and Tetsuya Kurihara. Originally founded in 1917, RIKEN remains Japan’s flagship institution in science and continues to be nearly exclusively funded by the Japanese government. About 3,000 scientists across many scientific disciplines, including medical sciences and biology, work across seven campuses throughout Japan. The Kobe Campus, shown above, was founded in 2002.

K computer and ICJ delegates: There is little doubt that in the near future, supercomputer technology will play an increasing role in the medical sciences and in the area of drug discovery. Already today, the K computer in Kobe (shown above), among the world’s fastest supercomputers, is engaged in medical research, among other. While at present, no cooperation between Bayer and K computer is planned, the increasing size of datasets generated by medical research and the increasingly complex interrelationship uncovered in fields such as oncology may change that. “Opportunities for partnering can be found in basic research, and across the entire value chain, from drug discovery to post launch, and the realm of possibility will likely expand even more as additional efforts are made to leverage artificial intelligence and share data,” explains Dr. Takahashi.

Kobe Biomedical Innovation Cluster (KBIC): As one of the largest biomedical clusters in Japan, KBIC already attracted RIKEN, K computer and several highly specialized hospitals as well as multiple medical companies. Bayer is in the early talks with the Foundation for Biomedical Research and Innovation to assess if any opportunity for cooperation may arise. Along those lines, Dr. Hans Lindner (right), and members of the ICJ from Bayer held meetings to explore potential avenues. Seiya Morikawa, KBIC Corporate Development Division (right), is outlining planned future activities for the region. Ultimately, the cluster will house a variety of healthcare-related topics including treatment, diagnosis, prevention, caregiving, and welfare, and may appeal to companies in pharmaceuticals, medical devices, and regenerative medicine.

Street life in Osaka: It is often said that the past meets the future in the land of the rising sun. Japan was the first country in Asia to independently modernize, and while Japanese continue to embrace and invent some of the newest technologies and aesthetics, many Japanese also hold up traditions, some of which dating back centuries. Today, the people of Japan live in one of the most developed and safe countries on earth, and according to the World Health Organization, also enjoy the longest life expectancy worldwide.

Dramatic shift: Japan has likely experienced the most drastic change in dietary preferences of any Asian country over the past decades.

Urbanization, rising incomes and changes in food supply have replaced sweet potatoes, barley and small side dishes of fish and vegetables with a more western diet. Scientists have observed a 2 - 3 fold increase in breast, colon and lung cancer in Japan between 1950 and 1975 alone. Increasing evidence suggest that such rapid diet changes may lead to a change in gene regulation for generations to come. The exact mechanisms underlying these so-called ‘epigenetic’ adaptions are not yet entirely understood and have now become subject to intense research.

Most epigenetic changes only occur within the course of one person’s lifetime but may last for multiple generations even though they do not involve changes in the underlying DNA sequence. While these epigenetic changes merely modify the activation of genes, many scientists now believe that epigenetic alterations are as important as genetic mutations in a cell's transformation to cancer and many other serious diseases. Underlying this regulation is a highly complex system network including ‘enhancers’ and ‘silencers’ which affect whether a gene is expressed. Thus, epigenetic research requires highly advanced molecular technology such as the methods Dr. Hodaka Fujii is developing at his laboratory.

Searching for a needle in a vast field of haystacks: Researchers must first isolate specific genomic regions while retaining their molecular interactions in order to understand the mechanisms of epigenetic regulation. Above, Dr. Hodaka Fujii (left) and Dr. Toshitsugu Fujita are evaluating recent research data. Being able to manipulate epigenetic regulation holds great promise for cancer prevention, detection, and therapy: “With the technologies we are developing at our laboratory we can identify such specific regions were epigenetic regulation takes place. I think that in the future, this can lead to the development of epigenetic drugs.”

Yoshida Campus, Kyoto University: Founded in 1897 and famed for producing ten Nobel Price laureates, two Fields Medalists and countless other world-class scientists, Japan’s second oldest university continues to be ranked as one of Asia’s leading researchoriented institutions. In 2014, Bayer and Kyoto University signed a two-year collaboration agreement to jointly identify candidates for possible research projects, in order to advance drug discovery and to conduct collaborative investigations. In 2017, the agreement was extended for another two years.

One of the research collaborations that came out of the comprehensive collaboration agreement between Bayer and Kyoto University is ongoing in the field of respiratory diseases: A scientist at the laboratory of Dr. Atsuyasu Sato conducts an experiment inside a sterile environment to avoid contamination of cell and tissue cultures from the environment. Dr. Sato and his colleagues are testing a hypothesis developed together with Bayer researchers in his comprehensive experiment set ups to study respiratory disorders using small molecule compounds provided by Bayer.

Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University.

Close cooperation, open innovation: Dr. Koji Yashiro, ICJ Alliance Manager for Bayer Yakuhin, discusses with Assistant Professor Atsuyasu Sato, MD, PhD, Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University. They are keen to find new ways to elucidate pathophysiological mechanisms of intractable respiratory disorders and to identify candidates for research subjects to advance drug discovery.

Office of the Bayer Open Innovation Center Japan: To further strengthen Bayer’s ties with Japan’s top-class scientists, ICJ organized a week of tightly packed events. Reiko Masuda, Pharma Communications Bayer Holding, and Reiko Yamada, ICJ Assistant, check minute-by minute schedules that perfectly align the 28 meetings between high-level academia with Bayer representatives from Germany and ICJ members held within just three days - not to mention the organizational requirements and logistical needs of running two open symposiums in Kyoto and Tokyo, and a full day of visits with local Japanese government representatives and science leaders in Kobe scheduled for the same week. The ICJ satellite office is located on campus of Kyoto University - a good indication that both sides seek a close partnership for mutual benefit.

Universities around the world are increasingly called upon to convert their research into benefits for society, and Japan is no exception. Close cooperation with leading pharmaceutical companies is one way to bridge the gap from laboratory bench to bedside.

The ‘Frontiers of Drug Discovery’ symposiums that ICJ held at Kyoto University (pictured above) and the University of Tokyo were open to anyone interested in the field and attracted more than 230 visitors, including many from academia, industry, and startups.

Prof. Masatoshi Hagiwara, Vice Dean, Graduate School of Medicine, Kyoto University, illustrated a worrisome trend observed recently: The decrease of returns from R&D investments in the area of drug development. Citing data from DeLoitte LLP, the absolute rate of return gradually fell from 10.1% in 2010 to only 3.7% in 2016. Open innovation could be a solution: “Firms can and should use external ideas as well as internal ideas, and internal and external paths to market,” adding that universities such as Kyoto University with their fully equipped research environment and willingness to share knowledge are ideally positioned to be a one-stop platform from drug screening to clinical trial.

The presentations were followed by a panel discussion that explored the future direction and possibilities of academia-industry collaboration for drug discovery. "Having a joint vision and mutually agreed goals is a key for a successful partnership between academia and industry," commented Dr. Karl Ziegelbauer during the panel discussion.

From left: Prof. Masakazu Toi, Deputy Director General, SACI; Prof. Masatoshi Hagiwara, Vice Dean, Graduate School of Medicine, Kyoto University; Dr. Karl Ziegelbauer, Head of Therapeutic Research Groups at Bayer; Prof. Hanno Wild, Head of Candidate Generation & External Innovation at Bayer.

Standing together in Kyoto: From left to right: Prof. Hanno Wild, Head of Candidate Generation & External Innovation at Bayer; Dr. Shunichi Takahashi, Head of ICJ; Prof. Masatoshi Hagiwara, Vice Dean, Graduate School of Medicine, Kyoto University; Dr. Karl Ziegelbauer, Head of Therapeutic Research Groups at Bayer; Prof. Masakazu Toi, Deputy Director General, SACI; Executive Vice President Shinji Asonuma,

Office of Society, Academia Collaboration for Innovation; Dr. Hans Lindner, Head of Global External Innovation and Alliances, Global Drug Discovery at Bayer; Heike Prinz, President of Bayer Yakuhin.

Building trust through mutual understanding: Dr. Shunichi Takahashi catches up with Grants4Targets winner Dr. Hodaka Fujii at the symposium in Kyoto. For both, one-on-one collaboration between academia and businesses is a vital element of drug discovery.

“Rather than focus on individual projects and technologies, however, we search for trustful partnerships at Bayer. The key to success will be to go beyond simple partnerships and to foster a ‘mutual understanding’ among all players,” explains Dr. Takahashi. Dr. Fujii feels much the same way: “My hope is to cure patients suffering from intractable diseases through the development of drugs; and I hope that the collaboration with Bayer can help me to make that dream come true.”

Following several long days of preparation and meetings with top scientists and delegates, Dr. Shunichi Takahashi spends the early night catching up on emails back in his Tokyo hotel room. Much has been achieved since the ICJ’s inception three years ago, yet much remains to be done: “Identifying research activities with great potential and nurturing them for the development of new drugs that will benefit humankind. That’s our mission and we hope that our efforts in this regard will not only support Bayer’s business, but also help strengthen the foundation of science in Japan.”

(All photos courtesy of © Armin Stelljes Ltd. / All rights reserved.)

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