NanoCarrier Co.,Ltd. Case Studies on Japan-Israel SMEs Collaboration 【2021/4/9】

NanoCarrier Co.,Ltd.

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NanoCarrier Co., Ltd. was established in June 1996 to apply nanotechnology to the development and commercialization of micellar nanoparticles for pharmaceuticals. The company opened a research center in Kashiwa City, Chiba Prefecture, in 2000, then the Tokyo office in 2003, and the laboratory in 2004. Four years later, in 2008, the company was listed on the Tokyo Stock Exchange's Mothers market. They were under-financed when they went public, and they moved their clinical development to Asia. They had funded successfully from 2012 to 2017, and they expanded globally by licensing and jointly researching with multiple major pharmaceutical companies. In 2017, the company in-licensed a drug development candidate to strengthen its management base and signed a domestic licensing agreement with Israel's VBL Therapeutics (VBL) for VB-111. It is now under development of the gene therapy product VB-111 in Japan. The current president, Tetsuhito Matsuyama, took office in November 2019. In the following year, 2020, the company merged with AccuRna, Inc., which specializes in nucleic acid therapeutics primarily focusing on unique drug delivery platforms, to strengthen the foundation for nucleic acid medicine development.




NanoCarrier's core technology, micellar nanoparticle (polymeric micelle) technology, was invented in Japan by Professor Kazunori Kataoka and his colleagues at the University of Tokyo Graduate School of Engineering. NanoCarrier is an R&D-based startup company specialized in drug discovery, and they focus on developing anti-cancer drugs. They aim to create a new value by using micellar nanoparticle technology as a drug delivery system (DDS) for treatment. The micellar nanoparticle technology can make artificial small nanosized capsules by using biocompatible materials such as poly(ethylene glycol)-poly(amino acid). The capsule contains drug and bioactive substances inside. The delivery efficiency can be increased by encapsulating the anti-cancer drug in nanoparticles. It aims to "reduce side effects" and "increase drug efficacy," which cannot be achieved with conventional formulations.

It can encapsulate various chemical compounds by selecting a type and structure of amino acids that form the inner core and bonding chemically. Also, covering the polyethylene glycol (PEG) surface ensures drug retention and stability in blood. It aims to create new medicines in oncology to contribute to society in drug development and manufacturing.

VBL, a biotechnology company, was established in Israel in 2000 and listed on the NASDAQ stock exchange in the U.S. VBL's drug VB-111 contains a gene that selectively kills endothelial cells creating blood vessels in a viral vector. It will kill cancer tissue by destroying blood vessels in it and cutting off nutrition and oxygen. The viral vector of VB-111 itself is expected to attack cancer cells by inducing an immune response in the body as an additional effect. Currently, VB-111 is undergoing Phase III clinical trials, mainly in the U.S. It seemingly can fill a significant medical need to establish an effective treatment for platinum-resistant ovarian cancer.

NanoCarrier was able to find VBL's VB-111 technology because of a worldwide search for a new DDS technology. It would enable drug delivery into the brain for the treatment of brain tumors. After discovering that VBL was conducting a clinical trial for glioblastoma, Nanocarrier’s business development department contacted VBL directly. They initially negotiated through conference calls. As VBL was nearing the end of its Phase III clinical trial for glioblastoma, it was the right time for licensing. The agreement was signed in 2017 after complicated negotiations on financial requirements. A lot could happen unexpectedly before starting an alliance. The practitioners' compatibility is also crucial and can significantly impact the outcome of the partnership. Two delegations from NanoCarrier visited Israel during the due diligence period before contract signing, and another team visited Israel right before signing an agreement for discussion. The VBL team also visited Japan for the meeting. NanoCarrier welcomed them with small flags of the two countries on the table, and the VBL representatives were so delighted that they brought them back to their country.

VBL and NanoCarrier signed a licensing agreement in 2017 for the development and commercialization of VB-111 in Japan, which gives NanoCarrier the exclusive rights to develop, supply, and sell the product in Japan. Under the terms of the agreement, NanoCarrier will be responsible for treating glioblastoma, ovarian cancer, and other solid tumors using VB-111 in Japan. They will bear the development costs and will have the right to market the drug in Japan. VBL received an immediate payment of $15 million from NanoCarrier when signing the agreement; they will receive up to $100 million as development milestone progress and sales milestone after approval.

Based on the positive interim analysis results from VBL's platinum-resistant ovarian cancer clinical trial in the U.S., NanoCarrier started preliminary consultation with the Pharmaceuticals and Medical Devices Agency (PMDA) on the Phase III clinical trial of VB-111 for ovarian cancer. They were planning to participate in the international joint clinical trial. They received The Cartagena Act approval for gene therapy, and the company is ready to conduct clinical trials in Japan. By doing so, Phase I and II trials in Japan will not be required, and they can start the Phase III clinical trial as early as FY2020, expecting about 30-40 Japanese cases to be implemented. More than 10,000 women are diagnosed with ovarian cancer annually in Japan, and more than 5,000 die each year. Therefore, establishing a clinical trial site in Japan will allow international clinical trials to process quickly worldwide. If positive results emerge, the application for approval can be filed in Japan.


Mr. Matsuyama, the president and CEO of NanoCarrier, joined Mitsubishi Corporation in 1986 and gained broad experience in Israeli companies and society, including startups, for 17 years. After leaving Mitsubishi Corporation in 2003, he was appointed as the president of a newly established biotech company by a venture capital firm. He has been in the healthcare business for a long time since then. The current friendly relationship between VBL and NanoCarrier can be attributed to President Matsuyama's deep understanding of Israeli culture and business.

VBL was concerned about the bureaucracy and slow decision-making process of large Japanese corporate organizations at the beginning of the negotiation. NanoCarrier responded in good faith, promising swift decision-making while fulfilling its governance obligations as a listed company. Mr. Matsuyama said that slow decision-making and ambiguous negotiation style of Japanese companies are already well known internationally. Breaking through these problems is one of the challenges for Japanese companies' globalization to ally with overseas companies.

Israeli companies target mainly U.S. and European markets, and they have a great sense of global awareness and outstanding technologies, which is very attractive to Japan. They make extensive use of a network of American Jewish doctors when clinical trials are required. The government has fully subsidized VBL to accelerate its development. In Israel, there are various sources of funding other than V.C.s, and there are many trustworthy practitioners with great flexibility. Israel also possesses many cutting-edge technologies based on its philosophy of being a "technology-oriented nation," and it is hoped that Japanese companies will actively approach Israel in the future.


Tetsuhito Matsuyama, President and CEO


Interview: Center on Finance and Innovation, Waseda University
Editor: Center for International Economic Collaboration

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