Biopharmaceuticals, medicines based on biological molecules such as proteins and nucleic acids, have already delivered effective treatments for a number of serious, often hard to treat diseases, such as Crohn’s disease and multiple sclerosis, dramatically improving patients’ quality of life.
The pharmaceutical industry is keen to expand its work on these novel drugs, but biopharmaceuticals still have a number of drawbacks which are hampering their broader application. For example, because these molecules tend to be complex and delicate, most biopharmaceuticals have to be injected; if they were administered orally (a more patient-friendly route), they would be destroyed by the harsh environment of the stomach. Furthermore, even once biopharmaceuticals are in the body, their large size means it is hard for them to get to their molecular targets.
By bringing together 14 academic groups, 7 pharmaceutical companies and 2 SMEs, the COMPACT project set out to reduce delivery and targeting bottlenecks for developing innovative biopharmaceuticals.
Better understanding of nanomedicines
One of the most significant project achievements is related to getting biopharmaceuticals from the injection site to the target that is causing the disease. For that purpose, researchers use nanocarriers, modifying their surface so that they bind to specific cells. COMPACT researchers discovered why this modification works in certain cases and not in others, which led to a better understanding of how nanomedicines work. The project also developed a novel nanoparticle to get a new type of therapeutic oligonucleotide into the lungs via inhalation.
More patient-friendly ways of administering drugs
Another important project outcome has to do with making the delivery systems for biological molecules more patient friendly. For example, insulin is a very effective treatment for diabetes but it has to be administered via injections. The COMPACT project researchers investigated whether insulin and similar biologicals could be delivered via tablets, which would be a more patient-friendly route. They showed that when insulin is taken via oral delivery, certain cell penetrating peptides can help in getting the molecules over the intestinal barrier into the blood. This represents the first important step towards the oral delivery of biological molecules.
Additionally, the project developed microneedles which can deliver peptides directly into the skin using a nanomedicine type of approach. These microneedles are so fine that they dissolve after they are inserted into the skin, representing a more patient-friendly alternative to traditional injections.
Important breakthrough in the blood-brain barrier
Another important achievement concerns the blood-brain barrier. The brain is a really isolated organ as there is a tight barrier between the blood and the brain cells. Getting across this barrier is a huge limitation in drug delivery. In this project, researchers identified potential new targets that can be used to get drugs into the brain. This is only at the target identification level at this stage but has led to a new IMI project which will explore those possibilities in more detail.
Database, cell banks and other achievements
Other important project achievements include:
- a wide repertoire of drug delivery systems, fully characterised and tested;
- in vitro and in vivo tools to study delivery, including transgenic reporter mice;
- a manually curated database containing over 1 200 entries with useful searchable information from the scientific literature on nonlipid nanoparticles and neurotrophic viruses;
- cell banks containing the most relevant cell lines and standardised protocols and a serum source to be used by all the partners throughout the consortium;
- a strong network of industry and academia to further explore collaborations via bilateral agreements and European funding.
In addition to the scientific achievements, the project generated significant socio-economic benefits. For example, during the course of the project two patents were filed: one for brain delivery and another for the nanocarrier system for lung delivery.
In order to build on the project achievements, a biotech company has also spun out from Oxford University. The company will look into developing exosomes –nano-sized lipid vesicles which shuttle proteins and genetic information between cells for the delivery of oligonucleotide-based therapeutics. The system is still at an early stage, but once developed, could be of great interest for pharmaceutical companies.
Furthermore, several companies which were not part of COMPACT are now also showing interest in the delivery systems developed within the project. They are collaborating with some of the COMPACT academic partners to see if these delivery systems could be used for their therapeutics. In the long run, these new collaborations could lead to the development of a new line of therapeutics.
For the benefit of industry, academia, SMEs
For academic partners this project was a great opportunity to work with the industry, use their R&D infrastructure, and learn what kinds of problems they encounter during the drug development process. The project also contributed to training of a new generation of pharmaceutical scientists that have a better understanding of the needs and limitations of the drug development process. During the course of the project, 19 PhD students got their doctorate degrees and 5 found jobs at the companies of industry partners.
The pharmaceutical companies benefitted from being able to test novel nanocarrier based delivery approaches directly with academic partners. They also benefitted from the network that has been created within the project, not just with academic partners and SMEs but also with other key players in industry.
The SMEs in the project benefitted from access to industry knowledge and resources, getting a close-up view of the drug development process, and from being treated as an equal partner in the project.
Benefits for patients
Biopharmaceuticals have the potential to improve the lives of many patients with diseases and conditions that are currently hard or even impossible to treat. By finding more effective ways of administering these drugs, and improving their ability to travel through the body to where they are needed, the COMPACT project outcomes will allow more patients to benefit from biopharmaceuticals. Furthermore, designing less invasive administration routes and reducing the dose (and therefore the side effects) and frequency of administration will help to improve patient compliance with treatments.
The project resulted in both tangible and non-tangible assets that will be useful for further research. Among the tangible assets are the transgenic mice for analysing biodistribution of nanocarrier systems. These are already accessible to researchers through a commercial company.
Non-tangible assets include more than 65 publications and the know-how that has been generated and will be further developed by researchers in the field, including those in follow-on IMI projects.
Achievements & News
Many new medicines are based on biological molecules such as proteins, peptides or nucleic acids. The goal of the COMPACT project was to shed new light on the obstacles these drugs (which are known as biopharmaceuticals) need to overcome to get to where they are needed in the body. As a result, the project has delivered drug delivery prototypes which may lead to the next generation of biologics-based medicines. ###The project also generated a spin-out company and two patents, demonstrating concrete socio-economic benefits. In an interview with the IMI Programme Office, project coordinator Ekkehard Leberer of Sanofi and academic coordinator Enrico Mastrobattista of the Utrecht University explain how the project transformed the biologics field, and why this wouldn’t have been possible without IMI. ‘I cannot imagine that this could have been done within one company or one institute,’ said Leberer. ‘To bring together all this industry experience, academic experience, nanomedicine, and imaging experience, that’s where IMI really was transformative.’
Many new medicines are based on biological molecules such as proteins or oligonucleotides. Although promising, most of these new drugs (known as biopharmaceuticals) cannot cross biological membranes and are therefore limited in reaching targets within the cell. This has so far limited the number of effective biopharmaceuticals available.### A new toolbox of methods and formulations, developed by IMI’s COMPACT project, will soon give scientists a step-by-step strategy to quickly and reliably assess both the quantity and the quality of the drug delivered to the cell’s interior, opening the way for the development of more effective drugs in the future. ‘The uptake of drugs into cells is one of the most critical steps in the delivery of biopharmaceuticals over biological barriers and robust methods that can monitor individual steps of this process were sorely needed’, said COMPACT scientific coordinator, Enrico Mastrobattista of Utrecht University. ‘COMPACT has invested time and resources to make robust new methods available for all consortium members and in due time, when all the work has been published, to the entire scientific community.’ The development of the toolbox was a joint effort between the industrial and academic project partners and parts of it were already published in the Journal of Controlled Release. ‘This achievement illustrates how public-private partnerships can synergise efforts’, said Mastrobattista. ‘IMI has helped in bringing together and aligning experts from industry and academia and boosted the collaboration by giving a financial impulse. The combination of academic curiosity and industrial project management skills has led to a fruitful and productive collaboration on a scale that would not be achievable outside of an IMI Project.’ This achievement contributes to the overall goal of the COMPACT project, which is to shed new light on the obstacles biopharmaceuticals need to overcome to get to where they are needed in the body.
The 2013 award for Hungarian Young Entrepreneur of the Year was won by Tamas Letoha, Chief Executive Officer of Pharmacoidea, which is a partner in two IMI projects.### Tamas was selected as the winner from over 400 public nominations from more than 50 small and medium-sized enterprises (SMEs) from a number of different business sectors. Dr Letoha, a medical researcher by training, received his award from the Hungarian Prime Minister, Viktor Orbán at the Role Model of the Year Award gala in January. The annual award is sponsored by the Role Model Foundation which was set up in 2013 to recognise successful Hungarian entrepreneurs under the age of 40. Tamas heads up Pharmacoidea Ltd. which specialises in R&D in drug discovery, functional food development and experimental cellular therapeutics against carcinomas. Pharmacoidea is a partner in two IMI projects, COMPACT and AETIONOMY. Tamas said that his achievements ‘were pretty much due to international R&D projects like AETIONOMY ’ and that he highly valued his connections with IMI.
ParticipantsShow participants on map
- Abbvie Deutschland GMBH & Co Kg, Wiesbaden, Germany
- Boehringer Ingelheim Internationalgmbh, Ingelheim, Germany
- Glaxosmithkline Research And Development LTD., Brentford, Middlesex, United Kingdom
- Merck Kommanditgesellschaft Auf Aktien, Darmstadt, Germany
- Novo Nordisk A/S, Bagsvaerd, Denmark
- Pfizer Limited, Sandwich, Kent , United Kingdom
- Sanofi-Aventis Deutschland GMBH, Frankfurt / Main, Germany
Universities, research organisations, public bodies, non-profit groups
- Bioneer A/S, Horsholm, Denmark
- Cardiff University, Cardiff, United Kingdom
- Helmholtz-Zentrum Fur Infektionsforschung GMBH, Braunschweig, Germany
- Kobenhavns Universitet, Copenhagen, Denmark
- Ludwig-Maximilians-Universitaet Muenchen, Munich, Germany
- Norges teknisk-naturvitenskapelige universitet - NTNU, Trondheim, Norway
- Stockholms Universitet, Stockholm, Sweden
- Universitat Wien, Vienna, Austria
- Universitat Zurich, Zürich, Switzerland
- Universiteit Gent, Gent, Belgium
- Universiteit Leiden, Leiden, Netherlands
- Universiteit Utrecht, Utrecht, Netherlands
- University of Helsinki, University of Helsinki, Helsinki, Finland
- University of Oxford, Oxford, United Kingdom
Small and medium-sized enterprises (SMEs)
- Pharmacoidea Fejleszto Es Szolgaltato Kft, Szeged, Hungary
|Name||IHI funding in €|
|Bioneer A/S||487 563|
|Cardiff University||675 228|
|Helmholtz-Zentrum Fur Infektionsforschung GMBH||550 611|
|Kobenhavns Universitet||984 291|
|Ludwig-Maximilians-Universitaet Muenchen||201 594|
|Norges teknisk-naturvitenskapelige universitet - NTNU||491 014|
|Pharmacoidea Fejleszto Es Szolgaltato Kft||559 740|
|Stockholms Universitet||618 030|
|Universitat Wien||837 742|
|Universitat Zurich||612 981|
|Universiteit Gent||491 133|
|Universiteit Leiden||786 582|
|Universiteit Utrecht||1 712 509|
|University of Helsinki||444 273|
|University of Oxford||731 618|
|Total Cost||10 184 909|