Practical Application and Industrial Use of Genetically Modified Silkworm Technology

「Although we have decided to discontinue new development aimed at producing pharmaceutical raw materials using genetically modified silkworms, antibodies and proteins produced in genetically modified silkworm cocoons have low nonspecific reactivity and are not subject to animal welfare requirements. Accordingly, in the short term, we will promote the substitution of target proteins, including antibodies used in research reagents and in vitro diagnostic products, as well as industrial applications such as cosmetic raw materials, with the aim of expanding production and improving manufacturing methods.」

「Initiatives involving genetically modified silkworms」

「This service has technology for producing target proteins in silkworm cocoons using genetic engineering techniques.」

「In our genetically modified silkworm development business, we had focused on research and development aimed at dramatically increasing the yield of recombinant proteins produced by genetically modified silkworms for use in producing pharmaceutical raw materials. However, as there is no clear prospect of achieving the target by the scheduled timeframe, and to concentrate the limited funds owned by our group on developing raw materials for in vitro diagnostic products and other products in the antibody-related business, we have decided to discontinue new development aimed at producing pharmaceutical raw materials using genetically modified silkworms.」

「We have decided to discontinue new development aimed at producing pharmaceutical raw materials using genetically modified silkworms. However, we will continue manufacturing, selling and improving the production methods for reagent products such as recombinant fibronectin and raw materials for in vitro diagnostic products already manufactured using genetically modified silkworms, as well as human-type collagen, through our antibody-related business.」

「Following the change in the method for producing anti-HIV antibodies from a genetically modified silkworm production system to a CHO cell production system, development is currently continuing under the leadership of CURED.」

「This business is focusing exclusively on basic research into developing useful proteins and improving the amount of such proteins produced in silkworm cocoons while controlling costs.」

「This business had been developing anti-HIV antibodies and conducting research and development aimed at producing pharmaceutical raw materials, but it has had to abandon production because of production-cost issues and other factors. The business regards resolving production-cost issues as the greatest challenge for the genetically modified silkworm business going forward and will concentrate on basic research to increase the yield of antibodies and proteins obtained from a single cocoon by approximately 10-fold.」

「However, in this business, research and development expenses are being incurred ahead of schedule because the company is intensively conducting basic research to increase recombinant protein yields by approximately 10-fold.」

「To date, the company has developed fibrinogen and anti-HIV antibodies produced in genetically modified silkworm cocoons and conducted research and development aimed at producing pharmaceutical raw materials, but it has had to abandon production of both products because of production-cost issues and other factors. The company regards resolving production-cost issues as the greatest challenge for the genetically modified silkworm business going forward and will concentrate on basic research to reduce the production cost of antibodies and proteins obtained from a single cocoon to approximately one-tenth.」

「Based on its accumulated data and experience, the company is conducting basic research to increase recombinant protein yields by at least 10-fold. It is also exploring ways to make effective use of the GMP manufacturing system developed through the manufacture of anti-HIV antibody drug substance, and will continue conducting research and development into new pharmaceutical seeds as a development-focused venture company.」

「Selling, general and administrative expenses decreased partly because capital investment declined following a change in the antibody manufacturing method in the genetically modified silkworm business (see the 6 August 2020 announcement, “Notice Regarding Change in Anti-HIV Antibody Manufacturing Method and Change in Use of Funds”).」

「In the genetically modified silkworm business, the company will improve and refine its technology for efficiently producing large quantities of target proteins in silkworm cocoons and expand its use in diagnostic products and cosmetic ingredients. It will also focus on developing GMP manufacturing technology at the Maebashi Research Center with a view to pharmaceutical applications.」

「The company has completed the joint filing of a domestic patent application relating to “Anti-HIV Antibody and Method for Producing Same” (see the 17 September 2019 disclosure, “Notice Regarding Patent Application for ‘Anti-HIV Antibody and Method for Producing Same’”). The research is making steady progress toward results.」

「The results of the efficacy and pharmacology studies are currently being compiled, and the company aims to disclose them during the first half of the fiscal year ending March 2020.」

「Efficacy and pharmacology studies are currently progressing smoothly, and the company is preparing to disclose the results. It has also held strategic consultations with the PMDA regarding the management of genetically modified silkworm strains and banks, which are key concerns in pharmaceutical manufacturing, and obtained agreement on its plans for ① the process for creating genetically modified silkworms and methods for managing strains, and ② quality and process control during large-scale rearing of genetically modified silkworms and its approach to the starting point for GMP management.」

「In this business, the company is developing manufacturing technologies to enable pharmaceutical production using genetically modified silkworms, with a focus on research and development. In particular, development of biopharmaceuticals involving anti-HIV antibodies is progressing smoothly.」

「At this stage, the Company is developing biopharmaceuticals, including anti-HIV antibodies, and the related manufacturing technology with the aim of realizing pharmaceutical manufacturing using genetically modified silkworms, with research and development as its business priority.」

「Because the joint research with CURED on this research and development theme progressed smoothly, the parties entered into an advanced joint development agreement in March 2018 on the premise that both would jointly promote commercialization.」

「The company aims to commercialize a breakthrough antibody therapeutic for treating HIV infection by dramatically enhancing the ADCC activity of the anti-HIV antibody owned by CURED using its genetically modified silkworm technology. It is currently developing silkworm-rearing and antibody-production technologies under a GMP framework using the pilot facilities at the Maebashi Research Center.」

「The company began developing an antibody therapeutic for adult T-cell leukemia (ATL) by producing in genetically modified silkworms a humanized anti-HTLV-1 antibody developed through joint research with the University of the Ryukyus.」

「In the genetically modified silkworm business, the company is pursuing activities aimed at commercialization. It has successfully produced the main monoclonal antibodies used in the Group’s products in silkworm cocoons using genetically modified silkworms and has begun manufacturing products by replacing the antibody raw materials currently used with silkworm-derived materials. In addition, through joint research with Nippi,Incorporated, it established a technology for producing laminin 511-E8 using genetically modified silkworms. Laminin 511-E8 is effective as a culture substrate for iPS cells and other cells, and the company sells the resulting laminin 511-E8 fragment (laminin 511-E8) as a raw material for research reagents.」

「In this business, the company is actively pursuing joint research with Astellas Pharma Inc. aimed at commercializing pharmaceuticals using human fibrinogen produced with genetically modified silkworms as a raw material, as well as joint development and other activities with CURED aimed at commercializing a breakthrough antibody therapeutic for curing HIV infection by dramatically enhancing the ADCC activity of CURED’s anti-HIV antibody using the company’s genetically modified silkworm technology.」

「In this segment, the company newly began operating the Maebashi Research Center and is actively pursuing joint research with Astellas Pharma Inc. aimed at commercializing pharmaceuticals using human fibrinogen produced with genetically modified silkworms as a raw material. It is also actively pursuing joint development and other activities aimed at commercializing a breakthrough antibody therapeutic that could cure HIV infection by dramatically enhancing the ADCC activity of an anti-HIV antibody owned by CURED using the company’s genetically modified silkworm technology.」

「As part of its joint research with CURED, the company is actively pursuing joint development and other activities aimed at commercializing a breakthrough antibody therapeutic for HIV infection by dramatically enhancing the ADCC activity of an anti-HIV antibody owned by CURED using the company’s genetically modified silkworm technology.」

「In the short term, the company will promote the replacement use of proteins, including antibodies used in research reagents and in vitro diagnostic products, as well as industrial applications such as cosmetic ingredients, and aims to secure specific production orders. Over the long term, it is actively pursuing joint research with Astellas Pharma Inc. aimed at commercializing human fibrinogen produced using genetically modified silkworms as a pharmaceutical raw material, and joint research with CURED aimed at developing anti-HIV antibodies as antibody therapeutics. It is also proceeding with investment in production facilities and related equipment for pharmaceutical raw materials, recruitment of talented personnel and preparations to establish a production system.」