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Building the product pipeline for commercial demonstration of Plant Molecular Factories

Periodic Reporting for period 1 - Pharma-Factory (Building the product pipeline for commercial demonstration of Plant Molecular Factories)

Reporting period: 2017-11-01 to 2019-04-30

Pharma-Factory is an industry driven Innovation Action to improve and consolidate the competitiveness and scientific leadership of European bioindustry in the field of Plant Molecular Farming. Plant Molecular Farming is the production of high-value compounds from plants through the use of biotechnology. The overarching aim of Pharma-Factory is to ensure delivery of new and innovative high-value products to the market. This will be achieved through the refinement, demonstration and regulatory and public acceptance of plant platforms as manufacturing systems that compete with and complement existing and conventional microbial or animal-based systems.

We will directly address the serious challenge of low acceptance of GMOs in Europe. We will design and use innovative, collaborative and participatory methods to: first, identify potential barriers and facilitators to the commercialisation of Plant Molecular Farming technologies, and subsequently co-develop tools to enable effective communication, ultimately to reduce barriers to acceptance of these new technologies across stakeholder groups. In our programme of work, we will hold a workshop for policy-makers and regulatory experts in government, which will highlight facilitators and barriers to PMF product development and communication strategies to increase acceptability of these products. Pharma-factory’s activities between academic and industrial partners will also bring new scientific and technological insights with broad scientific impact outside of the project, in areas including enhancing protein stability and subcellular targeting to increase productivity, glyco-engineering to enhance function and a variety of other strategies to broaden the versatility of Plant Molecular Factory platforms. Finally, the products offered by Pharma-Factory product-oriented partners will provide multiple tangible benefits to the end users.
During the first period of the grant, we have initiated work across all workpackages, and are already delivering results that are furthering the development of our Molecular Pharming products and smoothing their routes to market. In our social science workpackage, we have held scoping discussions with commercial partners and brought our SME partners together with academic partners in co-design workshops to establish a value proposition for each of our technologies and products. We have begin interacting with the public through 'quick-take' interviews and public engagement activities including Plant Designer at the London Design Festival, attended by ~1200 visitors; and a Public Engagement in Science event at St George’s “Spotlight on Science – Making medicines in tobacco” attended by 100 members of the public. Our regulatory issues workpackage has begun consultation at national and European levels to establish compliant frameworks for a range of plant manufacturing platforms and delivered a report on the regulatory pathway for each of our products.

Our scientific workpackages have begun to demonstrate the application of synthetic biology tools for industry compliant engineering of the plant manufacturing platform by delivering CRISPR/Cas9 mediated knock outs of RDR6 and SDS2 proteins in Brassica species and by using advanced molecular biology techniques to characterise UPMS, RPL29 and ptxD as potential selectable markers to replace antibiotic resistance marker for Phaeodactylum tricornutum. We are optimising yield of commercial product targets in multiple Plant Molecular Farming manufacturing platforms, including plant cell cultures, hairy root culture, algae and intact plants. Where yield cannot be improved, we have found novel solutions, such as the identification of an alternative viral display platform for diagnostic antigens in rheumatoid arthritis in WP7. We have extended existing validated plant molecular farming platform technologies into new product areas in workpackages targeting new therapeutics for HIV and diagnostics for rheumatoid arthritis and Sjogren’s syndrome and identified manufacturing solutions for “hard to produce” high value proteins such as Albajuna's target HIV-therapeutics. Good progress has also been made in the design of a Molecular Pharming kit aimed at researchers and educators to be made available in the latter stages of the project.
Pharma-Factory will undoubtedly advance Plant Molecular Farming beyond the state of the art, and we have ambitious expectations that this will happen on several levels.

1. Public and governmental acceptance and acceptability
Whilst the public may appear to hold strong views on GM technologies in plants, when it comes to Plant Molecular Farming, they are generally unfamiliar or at worst agnostic about the technology, but inclined to be favourable towards GM applications that offer true medical benefits. Whilst this may appear to be a good position, a pro-active approach is the most likely to result in the most favourable outcomes. Drawing together industry and academic stakeholders, we will introduce and explain Plant Molecular Farming to a range of end users across European regions, identifying barriers to acceptance and developing new novel approaches to lowering these barriers.

2. Scientific and technical advance
The scientific and technical advances that are the ambition of this proposal are all focused on advancing products. This project is not designed to discover new findings or techniques, but to identify approaches that will result in higher yields, better quality and greater product diversity. Public acceptance of the Plant Molecular Farming will only be worth anything if the science is strong enough to result in approved products. For this reason, increasing Plant Molecular Farming product availability to end users is the underlying mantra for all strategic considerations in this project.

3. Product pipeline development
SMEs developing platform technologies are usually only able to develop a handful of products in their early years. Given the development timeline for new biologics and the high failure rate, successful commercialisation, even with a strong product and a viable manufacturing process is a rare event. The ambition of Pharma-Factory is to help to establish the pipeline for products, by taking on some of the early risk in product selection and development. All of the SMEs involved in Pharma-Factory have dedicated part of their work packages to the exploration of new products (or product classes like glycoproteins or monoclonal antibodies).

4. Industry engagement
The pharmaceutical industry tends to take more note when technologies become validated and target products approach the market. A criticism that is often levelled at Plant Molecular Farming is the lack of engagement by major pharmaceutical companies, although in recent years this has softened with major investments made by Bayer AG, Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., and Denka Seiken Co. Ltd. However, the ambition of Pharma-Factory is to elevate the developmental status of multiple European SME’s and to help establish a wave of Plant Molecular Farming products alongside transparent regulatory pathways and positive public opinion. Together, this will make a forceful statement about the viability and future of Plant Molecular Farming, which major industrial players will not be able to ignore.
Molecular Farming technology diagram
Pharma-Factory team
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