SCALE UP OF GLYCAN-COATED GOLD PARTICLES

OVERVIEW

OPPORTUNITY

INNOVATION

IMPACT

PROJECT WORKPLAN

CONSORTIUM

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OVERVIEW

SCALE UP OF GLYCAN-COATED GOLD PARTICLES

NANOFACTURING will design and build both pilot and large scale manufacturing lines for the production of nanopharmaceuticals.

The project will focus on the scale up of glycan-coated gold nanoparticles, the latest generation of nanomedicines. A number of nanopharmaceutical formulations have been shown to hold considerable potential for enabling more effective and less toxic therapeutic interventions.

Nanofacturing aims to address the bottlenecks in the delivery of these medicines to the market

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OPPORTUNITY

The European Technology Platform for Nanomedicine reports that in excess of 700 industrial organisations, including SME’s, are working in the field of Nanomedicine.

There are numerous nanopharmaceuticals in development across Europe. Progress in translating these innovative medicines into commercial successes has been limited by the inability to manufacture batches at the required scale and in line with stringent quality control measures required for medical products. The quantities required for clinical studies are modest, but such pilot processes do not fit easily into existing manufacturing plants. The lack of a pilot manufacturing supply chain is especially problematic for SMEs and other organisations that do not have the resources to develop the processes in-house.

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INNOVATION

NANOFACTURING’s core technology relates to glycan-coated gold nanoparticles.

The small size of gold nanoparticles creates several critical qualities for drugs based on this technology:

• The ability to pass through normal pore sizes in blood vessels, allowing delivery to many disease sites

• Rapid clearance from the body by excretion in the urine, preventing the potential for retention of the nanoparticles in the body

Selective therapeutic treatments are made possible due to these unique properties exhibited by Gold nanoparticles, which can be used to deliver drugs that otherwise demonstrate low solubility and poor pharmacokinetics.

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IMPACT

Oncology

Central Nervous System

Anti-viral

Endocrine

NANOFACTURING’s key glycan coated Gold Nanoparticle technology has a

number of potential applications, across a variety of healthcare indications.

The global market for nanomedicine applications, including neurology,

cardiovascular, anti-inflammatory, anti-infective, and oncology, is expected to

reach a value of €157 billion by 2019.

• 50% lifetime risk of developing cancer

• Many unmet clinical needs

• NANOFACTURING will focus on brain, liver, ovarian and pancreatic cancer treatments

• Very few small and almost no large molecules are able to cross the Blood Brain Barrier

• There are a very limited number of effective drugs for the majority of CNS disorders

• Potential to treat Alzheimer’s, Parkinson’s, Stroke, Autism etc.

• Most viral infections have no known treatment

• Many lethal viruses are currently untreatable

• NANOFACTURING aims to develop a new type of treatment utilising GNP technology

• Diabetes is considered the fifth leading cause of death in developed countries

• Prevalence of diabetes has been increasing globally at an annual rate of 5%

• NANOFACTURING aims to scale up manufacture of a unique transbuccal insulin delivery method

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PROJECT WORKPLAN

The workplan for NANOFACTURING has been divided into eight work packages, including Assessment, Scale Up, Process

Development, Management, Piloting, and Dissemination and Exploitation activities.

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Project Management and Reporting

Assessment and Specification of the Technology Platform Requirements

Scale-Up of Ligand Manufacture

Scale up of existing Reactor-based NP manufacture

Process development and scale up of solid core NP and peptide linked NP manufacture

Physicochemical and biocompatibility characterisation of NPs

Evaluation and generation of Concept Designs for a full scale manufacturing plant

Exploitation and Dissemination

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CONSORTIUM

NANOFACTURING will leverage and enhance the expertise and knowledge

of the nine companies and academic centres of excellence across Europe that

form the consortium, leaving a legacy that will support the further growth of this

emerging high potential technology.

Midatech Pharma is a nanomedicine Group focused on the development and commercialisation of multiple, high-value, targeted therapies for major diseases with unmet medical need.

Midatech is advancing a pipeline of novel clinical and pre-clinical product candidates based on its proprietary drug conjugate and sustained release delivery platforms focusing on the key therapeutic areas of diabetes, cancer and neuroscience/ ophthalmology.

Midatech’s strategy is to develop its products in-house in rare cancers and with partners in other indications, and to accelerate growth of its business through strategic acquisition of complementary products and technologies.

Two companies within the Midatech Group are directly participating in the Nanofacturing Project:

• Midatech Pharma España (Spain) is the Technology Transfer and R&D Centre and Manufacturing Unit coordinating Nanofacturing Project.

• Midatech Limited (UK) provides scientific expertise and administrative support for the Nanofacturing Project.

The Centre for Process Innovation (UK) is part of the UK government’s High Value Manufacturing Catapult network and aims to bridge the space between invention and commercialisation, supporting the translation of promising research into commercial and economic success.

CPI bring broad interdisciplinary knowledge in biopharmaceutical manufacture, nanotechnology, green chemistry and industrial biotechnology, with over 10 years’ experience of developing and demonstrating innovative process technologies.

In addition to working with Midatech Pharma Group to optimise and scale up their existing batch process, CPI will draw on their expertise in the development and scale up to create a new, sustainable, scalable, clinically compliant manufacturing process for nanopharmaceuticals.

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The Centre for BioNano Interactions (CBNI), led by Prof. Kenneth Dawson, is a multi-disciplinary platform for NanoSafety and NanoMedicine located at the National University of Ireland in Dublin.

CBNI is one of the world’s leading centre’s of knowledge for bionanointeractions applied to the fields of nanosafety, nanobiology and nanomedicine, pioneering many of the new techniques and approaches in the arena. CBNI has international reputation, strong links and co-operations with academia, institutions, industry, and governments world-wide.The Centre brings to the Nanofacturing project advanced technologies for nanoparticle (NP) characterisation, the instrumentation and the methodologies for multi-biological characterisation, assay screening for in vitro nanomaterial toxicity.

This functional and biological aspect of characterisation will support any future submission for these nanopharmaceuticals.

Applus+ Laboratories (LGAI Technological Centre S.A.) is a division of the Applus+ Group specialising in testing, product development and product certification.

Our Fine Chemicals & Pharma area focuses on chemical process development and industrialisation. Applus+ has state of the art analysis and synthesis laboratories and a GMP pilot plant located next to a University Campus in Bellaterra (Barcelona, Spain).

Our expertise and our facilities allow us to participate in all the stages of the development of chemical processes:

• Process research, process optimization and tech transfer of APIs development

• Analytical methods development and validation

• Scale-up and optimization of chemical processes

• API production under GMP

Applus+ Laboratories invests strategically in R&D+I projects and collaborate in national and international R&D+I projects, partnering with different industries such as fine chemical, pharmaceutical and biopharmaceutical. Applus+ Laboratories is one of the partners involved in the project Nanofacturing. Our researchers will focus their efforts on developing a synthetic route for the manufacture of the ligands compatible with industrial scale manufacturing processes and in accordance with the pharmaceutical regulations.

ProChimia Surfaces is a privately held company established in 2005 and located in Sopot, Poland. Capitalising on expertise in chemistry, nanotechnology and biotechnology ProChimia Surfaces delivers state-of-the-art solutions for modification of surfaces and materials.

Company business main components are: (I) design and manufacture of metal nanoparticles functionalized with ligands (charged, pH-sensitive, biospecific) and (II) synthesis and market of chemicals for self-assembled monolayers (SAMs). The compounds we design are unique and can be used to modify e.g. gold, silver, silicon, oxide or composite surfaces. The SAMs formed by our chemicals impart the surfaces being coated with various properties, including bioresistance to non-specific binding of proteins or cells, reactivity toward specific molecules, controlled hydrophobicity, electrochemical or optical activity and more. The company also offers custom research services in the fields of chemical and nanosynthesis.

During the 4-year project ProChimia’s specialists will contribute to the development of the optimised and pharma-industry applicable process of thiolated ligands synthesis for gold nanoparticle construction: a key component of Midatech’s GNP technology.

GalChimia helps the different actors of the pharmaceutical industries, providing high quality organic chemistry services.

Founded in 2001, we have become Spain’s leader in organic synthetic chemistry and organic chemistry synthesis. Our expert, dedicated team of chemists have found a productive outlet for their obsession with chemistry, providing Custom Synthesis, Medicinal Chemistry, Process Development, Reaction Optimisation, and Analytical Services.

Nowadays, as biotechnology or nanotechnology based therapy is growing there is still a need for chemistry. Indeed, in the case of nano-particles, they have to be linked to another molecule, either biologic or chemical, to be functionally active. This union is made by a chemical linker and is what we are doing for the Nanofacturing project. We are developing and synthesising new linkers that are able to make the union between the nano-particle and another molecule.

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Supramolecular NanoMaterials and Interfaces Laboratory (SuNMIL) is located in Ecole Polytechnique Fédérale de Lausanne (EPFL), a federal university in Switzerland.

The laboratory, led by Professor Francesco Stellacci, consists of around 15 members at senior scientist, post-doctoral, and PhD level. Two thirds of the laboratory work is around gold nanoparticles synthesis, characterisation, and application. The main group expertise lies in the characterisation of the nanoparticles ligand shell. Dr. Quy Khac Ong is a post-doc at SuNMIL, he is the leading expert in scanning probe microscopy characterisation of ligand coated gold nanoparticles.

Dr. Samuel Jones is a post-doc at SuNMIL with extensive expertise in nanoparticle characterisation. Within the Nanofacturing project SuNMIL will lead work that is dedicated to the physical characterisation of nanoparticles suspensions.

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The IRCCS Istituto Tumori di Bari is a public, juridical body of national relevance, confirmed by ministerial decree in February 2006, and specialising in Oncology.

In 2010, the Institute applied as Centre of Excellence in Oncology which was granted by the International Commission of the Organisation of European Cancer Institutes (OECI) in October 2014. The Nanomedicine group of Dr. Silke Krol at IRCCS Bari was established in 2016 and aims in developing functionalized nanoparticles for diagnosis and therapy of different types of diseases such as cancer, and infectious diseases. The spectrum of designed NPs covers soft material such as polyelectrolyte-DNA-SiRNA constructs as well as gold nanoparticles of different size and more importantly different surface functionalities. These NPs are designed to use specific disease related peculiarities such as pH or cell surface receptors.

Nanofacturing has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 646364

www.nanofacturing.eu

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