Ministry of Economy, Trade and Industry 1/23/23 Ministry of Economy, Trade and Industry 1/23/23

Investing in Biotech

To help Japan capture a market forecast to grow to up to $4 trillion by 2040, METI has created an $8 billion fund to support biomanufacturing, a field that encompasses technologies which leverage genetic technology to maximize the ability of microorganisms to produce substances.

From plastics that melt in the sea to cultured foie gras, Japan is pushing innovative technologies forward with government support

Presented in partnership with the Ministry of Economy, Trade and Industry

In terms of taste, IntegriCulture’s prototype cultured foie gras has been praised by culinary experts as having a good balance of richness and sweetness.

A decade on from Dr. Shinya Yamanaka’s win of a Nobel Prize for his research into induced pluripotent stem cells, or iPS cells, Japan is lagging in bringing biotechnology to a market forecast to grow to up to $4 trillion by 2040.

To help capture this huge opportunity, Japan’s Ministry of Economy, Trade and Industry (METI) revealed plans last fall for an $8 billion (¥1 trillion) fund to support biomanufacturing. The field encompasses technologies that leverage genetic technology to maximize the ability of microorganisms to produce substances.

Hirokazu Shimoda, director of METI’s Bio-Industry Division, explained why the country plans to go big on bio.

“It is only a matter of time before the global manufacturing industry is replaced by bioprocesses,” he said. “That’s why we are making medium- to long-term investments on the scale of about ¥1 trillion to build a system for companies in the biotechnology and drug discovery markets to develop and manufacture in Japan, then earn money in the global marketplace.”

As well as driving economic growth, biomanufacturing is also expected to be key in solving global issues such as marine pollution, global warming, and food shortages. Some top players in Japan’s biomanufacturing field are already making a difference in those areas.

Green Planet

In 2011, Kaneka Corporation achieved the world’s first commercial production of plastic that degrades in the ocean. The Osaka-based company plans to quadruple the production capacity of its biodegradable biopolymer called Green Planet to 20,000 tons in January 2024.

Kaneka began developing Green Planet in the early 1990s, when global environmental problems such as global warming began to emerge. The project was launched due to the strong desire of researchers to provide environmentally friendly products that don’t depend on fossil fuels.

Green Planet has qualified for the BiomassPla Identification and Labelling system, awarded to materials composed of biomass. It has also received the OK Biodegradable MARINE certification, issued by TÜV Austria Belgium NV/SA for materials that biodegrade in seawater.

Osaka-based Kaneka Corporation plans to quadruple the production capacity of its biodegradable biopolymer called Green Planet to 20,000 tons in January 2024.

Currently, Green Planet is used in straws, plastic shopping bags, cutlery, food containers and agricultural supplies. Seedling pots made with the material can be left to biodegrade after being buried in the soil. Kaneka is studying the material’s effects on natural cycles, including changes to bacteria in the soil.

“The focus of our research is to expand the range of physical applications for which Green Planet can be used,” explains Dr. Shunsuke Sato, a researcher at Kaneka’s Agri-Bio & Supplement Research Laboratories. According to the company’s own estimates, the combined annual production volume of plastic alternatives in Japan, the United States, and Europe currently is about 25 million tons. The market for Green Planet as a substitute for traditional plastic is expected to expand as regulations tighten and awareness grows.

Looking to capture this demand, Kaneka is focusing on carbon dioxide (CO2) as a new raw material for mass production of Green Planet. The goal is to recycle CO2 using microorganisms thereby creating a new process of manufacturing that can address both environmental problems and economic development. Sato explains: “We have the technology to do this in the lab. For mass production, we need to develop a culture process that efficiently converts gas components, such as CO2 and H2 [Dihydrogen], into Green Planet.”

Redefining Meat

Culturing has deep roots. For hundreds of years, humans have used and improved upon it to make wine, cheese, and more. In recent years, new culturing techniques have unlocked the process for making lab-grown cultured meat, redefining what we believed to be possible.

One pioneer of this movement is IntegriCulture Inc. As competition in the development of cultured meat heats up globally, this Japanese startup is the world’s first to succeed in producing cultured foie gras. Dr. Yuki Hanyu, IntegriCulture’s CEO, began research in 2014 on the CulNet System, a unique cell culture technology for manufacturing cultured meat. In 2019, he completed a prototype of cultured foie gras using duck liver cells.

The expansion of the worldwide market for cultured meat provides a tailwind for development. According to market forecasts by US consultancy A.T. Kearney, cultured meat will make up 35 percent of the meat market by 2040. Hanyu believes that the spread of cultured meat will depend on price, taste, and consumers’ belief in its safety.

In terms of taste, IntegriCulture’s prototype cultured foie gras has been praised by culinary experts as having a good balance of richness and sweetness. The first commercial sales are planned for 2024 in Singapore, a market with a precedent. In 2020, Singapore approved the sale of cultured chicken developed by a US company. Domestically, IntegriCulture is aiming to begin sales in 2025, but Japan’s screening standards for areas such as safety have not yet been decided.

The potential advantages that come with cultured meat are enormous. IntegriCulture’s CulNet System makes it possible to produce cultured meat at about one ten-thousandth the cost of conventional culture methods. With conventional methods of cultivation, ingredients contained in the blood, such as the serum necessary for cell culture, are expensive and seen as an obstacle to commercialization. However, with CulNet System, IntegriCulture has succeeded in maintaining the appropriate nutritional content without using expensive ingredients. It can also culture cells from various animals including fish.

IntegriCulture plans to sell the CulNet System to food manufacturers and other organizations, and to work together with them to develop technologies that will enable mass production.

“Leveraging our core strength of engineering technology, we want our system to find its proper place in the world,” said Hanyu, who first got involved in so-called cellular farming because he wanted to make the cultured meat he read about as a child in science fiction novels. To this day, he continues to strategize about what he can make with biotechnology, taking inspiration from his beloved world of science fiction.

Companies such as Kaneka and IntegriCulture are just the tip of the iceberg in terms of Japanese biotechnology’s true potential. “Japan is good at the zero-to-one stage of research and development, but is often less adept at scaling up as an industry on the global level,” explains Kaneka’s Sato. That’s exactly what METI aims to change, helping these pioneers and other like them with the funding they need to mass produce and commercialize their innovative biotechnologies.

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Tim Romero 12/24/21 Tim Romero 12/24/21

The Case of the Missing Startups

University and government venture funds play a much larger role in Japan than they do in Western countries. Yet we see fewer biotechnology startups here compared with, say, the United States, which is home to eight of the top 10 highest-funded ventures. Why?

Why biotechs find it hard to get going in Japan

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I explored this with Dr. Hiroaki Suga, co-founder of biotech company PeptiDream Inc., in a recent episode of my podcast Disrupting Japan. A professor at the University of Tokyo, Suga did his post-doctoral study under Nobel Prize-winning biologist Jack Szostak at Harvard Medical School. As an academic and a researcher, Suga knows well the dynamics at play in biotech development and application in Japan.

With PeptiDream, which has created a platform for the discovery of highly diverse, non-standard peptide libraries that can be developed into peptide-based therapeutics, Suga has taken a different approach to funding. And it has paid off.

Founded in 2006, PeptiDream is now worth more than $3 billion and collaborates with many of the world’s largest pharmaceutical companies, including American Chamber of Commerce in Japan (ACCJ) members Eli Lilly Japan K.K., Bayer Yakuhin, Ltd., AstraZeneca K.K., and Novartis.

Less is More

What I learned from our discussion is that, in this situation, smaller investments may lead to better results.

“If you have $10 million, you will just burn through it,” Suga said, adding that less capital will keep you focused and get results that can lead to bigger things.

In PeptiDream’s seed round, it received $1 million from The University of Tokyo Edge Capital Partners Co., Ltd., a Japan-based seed- and early-stage deep-tech venture capital firm.

With limited funds, “You need to really develop technology that will allow you to collaborate with big pharmaceutical companies,” Suga explained. These companies set criteria, and don’t give you money immediately. “Once you reach [one set of] criteria, you can get money. Then you get to another stage and you get more money,” he said.

This approach carries less risk for pharmaceutical companies, and Suga sees little risk for PeptiDream, because he is confident that they can meet the criteria.

Obstacles

This unusual approach has worked well for PeptiDream, so why don’t we see more biotech startups succeeding this way in Japan?

Suga said there are several reasons.

“Venture capitalists are not investing in risky companies, and biopharmaceutical companies are high risk,” he explained. “If you are developing business software, after six months, you know if it isn’t working. But drug development is a long-term commitment.”

“The first is that venture capitalists are not investing in risky companies, and biopharmaceutical companies are high risk,” he explained. “If you are developing business software, after six months, you know if it isn’t working. But drug development is a long-term commitment. Venture capitalists have to wait, and they may not be able to do so. They may need to wait 10 years to realize the potential, but they are looking for five.”

“The second reason is that Japanese society prefers to go with what’s known,” he continued. In this case, it means that talent heads for the largest pharmaceutical companies, which are seen as stronger and a safe harbor. “For example, all my students go to big pharma. They don’t go to PeptiDream.”

But this isn’t so much a case of risk aversion—often cited as an obstacle to success in Japan—as one of familiarity. Their parents know the names of the big players, but not of small ones such as PeptiDream.

Large Japanese companies tend to have little interest in helping smaller ones. This chasm is one that the ACCJ is attempting to bridge with its Healthcare x Digital initiative, which completed its second annual competition in November.

Spin-off vs. Startup

The third obstacle that Suga cited is the fact that many startups in Japan are research units that have been spun off from large companies that chose to leave Japan. “They had a very good team here, so they decided to spin off. They already have a background from big pharma and continue doing [what they were doing],” he explained. “That means that they aren’t hugely different from the big companies.”

In the end, Suga said that the biggest change that needs to take place for Japan to become more fertile ground for biotech startups must be made at the university level.

“Professors really need to work hard to get technology to be very practical, to be very robust. You really have to put forth effort to get to the end,” he said. “Then, the Japanese government needs to support this type of research. That’s very critical.”